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Last Updated: March 28, 2024

Claims for Patent: 8,129,371


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Summary for Patent: 8,129,371
Title:Thienopyrimidine and pyrazolopyrimidine compounds and their use as mTOR kinase and PI3 kinase inhibitors
Abstract: The invention relates to thienopyrimidine and pyrazolopyrimidine compounds of the Formulas (Ia) and (IIa), ##STR00001## or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein compositions comprising the compounds, and methods for making and using the compounds.
Inventor(s): Zask; Arie (New York, NY), Kaplan; Joshua Aaron (Nyack, NY), Verheijen; Jeroen Cunera (Highland Mills, NY), Curran; Kevin J. (Congers, NY), Richard; David James (Warwick, NY), Ayral-Kaloustian; Semiramis (Tarrytown, NY)
Assignee: Wyeth LLC (Madison, NJ)
Application Number:12/251,712
Patent Claims:1. A compound of the Formula (Ia): ##STR00078## or pharmaceutically acceptable salts thereof, wherein: het is a 5-10-membered bridged heterobicyclyl-group containing at least one oxygen atom, at least one nitrogen atom, and optionally additional heteroatoms selected from oxygen, sulfur and nitrogen, and is connected to the pyrazolopyrimidinyl group through one of the nitrogen atoms; R.sup.20 is independently selected from hydrogen, halogen, hydroxyl, C.sub.1-C.sub.2alkoxy, NH.sub.2, NH(C.sub.1-C.sub.2alkyl), N(C.sub.1-C.sub.2alkyl)(C.sub.1-C.sub.2alkyl), NHC(O)(C.sub.1-C.sub.2alkyl), N(C.sub.1-C.sub.2alkyl)C(O)(C.sub.1-C.sub.2alkyl), NHC(O)H, C(O)NH.sub.2, C(O)NH(C.sub.1-C.sub.2alkyl), C(O)N(C.sub.1-C.sub.2alkyl)(C.sub.1-C.sub.2alkyl), CN, C(O)OH, and C.sub.1-C.sub.4alkoxycarbonyl; t is 0-16; each R.sup.1 is independently halogen; C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.8alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.1-C.sub.6alkoxy optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkenyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkynyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8carbocycle; C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; heteroaryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; C.sub.1-C.sub.8acyl; C.sub.1-C.sub.8alkoxycarbonyl; C.sub.1-C.sub.8alkylcarboxy; --N--(C.sub.1-C.sub.6)alkylamido; hydroxyl; NR.sup.4R.sup.5; --NHC(O)NR.sup.4R.sup.5; --NHC(O)NHNR.sup.4R.sup.5; --NHC(O)OR.sup.6; --NH(SO.sub.2)NH--C.sub.1-C.sub.6alkyl; --NH(SO.sub.2)NH--C.sub.6-C.sub.14aryl; --NHC(S)--NR.sup.4R.sup.5; --NHC(.dbd.N--CN)--NR.sup.4R.sup.5; --NHC(.dbd.NR.sup.4)--NR.sup.4R.sup.5; --N.dbd.C(S--C.sub.1-C.sub.6alkyl)(NH--C.sub.1-C.sub.6alkyl); or --N(H)--C(.dbd.N--(CN))-(O--C.sub.6-C.sub.14aryl); m is 0, 1, 2, 3, or 4; r is 0 or 1; each R.sup.4 and R.sup.5 is independently --H; a 4- to 7-membered monocyclic heterocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, heterocyclylalkyl, C.sub.7-C.sub.24arylalkyl, C.sub.1-C.sub.8acyl, C.sub.1-C.sub.8alkoxycarbonyl, C.sub.1-C.sub.8alkylcarboxy, halo, --C.sub.1-C.sub.8haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl optionally substituted with --NH.sub.2, -alkylamino, or -dialkylamino, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido optionally substituted with --NH.sub.2, -alkylamino, or -dialkylamino, --C(O)NH.sub.2, -alkylcarboxamido, heterocycle optionally substituted with C.sub.1-C.sub.6alkyl, --S(O).sub.2-heterocyclylalkyl optionally substituted with C.sub.1-C.sub.6alkyl, heterocyclylalkyl optionally substituted with C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy optionally substituted with --NH.sub.2, -alkylamino, -dialkylamino, heterocycle, or hydroxyl, --C(O)NH--NH.sub.2, --C(O)NH--NH(C.sub.1-C.sub.6alkyl), --C(O)NH--N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --C(O)NH-heterocycle, --SO.sub.2(C.sub.1-C.sub.6alkyl), --CN, and --NO.sub.2; heteroaryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl optionally substituted with --NH.sub.2, -alkylamino, or -dialkylamino, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -aminoalkyl, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido optionally substituted with --NH.sub.2, -alkylamino, or -dialkylamino, --C(O)NH.sub.2, -alkylcarboxamido, heterocycle optionally substituted with C.sub.1-C.sub.6alkyl, --S(O).sub.2-heterocyclylalkyl optionally substituted with C.sub.1-C.sub.6alkyl, heterocyclylalkyl optionally substituted with C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy optionally substituted with --NH.sub.2, -alkylamino, -dialkylamino, heterocycle optionally substituted with C.sub.1-C.sub.6alkyl, or hydroxyl, --C(O)NH--NH.sub.2, --C(O)NH--NH(C.sub.1-C.sub.6alkyl), --C(O)NH--N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --C(O)NH-heterocycle, --SO.sub.2(C.sub.1-C.sub.6alkyl), --CN, and --NO.sub.2; --C.sub.3-C.sub.8-carbocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, alkylcarboxyamido, and --NO.sub.2, wherein any two hydrogen atoms on the same carbon atom of the carbocyclic ring can be replaced by an oxygen atom to form an oxo (.dbd.O) substituent, and wherein any two hydrogen atoms on the same carbon atom of the carbocyclic ring can be replaced by an alkylenedioxy group so that the alkylenedioxy group, when taken together with the carbon atom to which it is attached, forms a 5- to 7-membered heterocycle containing two oxygen atoms; heterocyclylalkyl optionally substituted with C.sub.1-C.sub.6alkyl; C.sub.6-C.sub.10carbocycle; bicyclic heterocycle; or C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy optionally substituted with --NH.sub.2, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, -alkylcarboxamido optionally substituted with --NH.sub.2, -alkylamino, or -dialkylamino, --C(O)-heterocycle optionally substituted with C.sub.1-C.sub.6alkyl, and C.sub.3-C.sub.8-carbocycle; or R.sup.4 and R.sup.5 when taken together with the nitrogen to which they are attached can form a 3- to 7-membered heterocycle wherein up to two of the carbon atoms of the heterocycle can be independently replaced with --N(R.sup.7)--, --O--, --C(O)--, or --S(.dbd.O).sub.s; each s is independently 1 or 2; R.sup.6 is C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl optionally substituted with --NH.sub.2, -alkylamino, or -dialkylamino, heteroaryl, and C.sub.3-C.sub.8-carbocycle; heterocyclylalkyl optionally substituted with C.sub.1-C.sub.6alkyl; C.sub.6-C.sub.10-carbocycle; bicyclic heterocycle; or C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; R.sup.7 is hydrogen; C.sub.1-C.sub.8acyl; C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.3-C.sub.8-carbocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, alkylcarboxyamido, and --NO.sub.2; C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; heteroaryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; alkylamino; or arylamino optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; with the proviso that when m>1, two R.sup.1 groups attached to adjacent carbon atoms can be taken together with the two carbons to which they are attached to form a fused 5- to 7-membered aromatic ring wherein up to 2 of the carbon atoms of the fused ring can be replaced with --N.dbd., --N(R.sup.7)--, --O--, or --S(.dbd.O).sub.s--; R.sup.2 is hydrogen; halogen; C.sub.1-C.sub.8acyl; heterocycle; heterocyclylalkyl; C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkenyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkynyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; or heteroaryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -aminoalkyl, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; R.sup.3 is hydrogen; C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl),

--NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkenyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkynyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.1-C.sub.8acyl; C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; heteroaryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; C.sub.7-C.sub.24arylalkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; heterocyclylalkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8carbocycle; C.sub.1-C.sub.6hydroxyalkyl-; alkylcarboxy; alkoxycarbonyl; C.sub.1-C.sub.6 perfluoroalkyl; --S(O).sub.S--C.sub.1-C.sub.6alkyl wherein the C.sub.1-C.sub.6alkyl of --S(O).sub.S--C.sub.1-C.sub.6alkyl is optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, alkylcarboxyamido, and --NO.sub.2; --S(O).sub.S-aryl wherein the aryl of --S(O).sub.S-aryl is optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, alkylcarboxyamido, and --NO.sub.2; C.sub.3-C.sub.8-carbocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino optionally substituted by hydroxyl, -dialkylamino, heterocycle optionally substituted with C.sub.1-C.sub.6alkyl, --NH--N(C.sub.1-C.sub.6alkyl).sub.2, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, alkylcarboxyamido, and --NO.sub.2, wherein any two hydrogen atoms on the same carbon atom of the C.sub.3-C.sub.8-carbocycle ring can be replaced by an oxygen atom to form an oxo (.dbd.O) substituent, wherein any two hydrogen atoms on the same carbon atom of the C.sub.3-C.sub.8-carbocycle ring can be replaced by an alkyleneoxy group so that the alkyleneoxy group, when taken together with the carbon atom to which it is attached, forms a spiro-fused 5- to 7-membered heterocycle containing an oxygen atom, and wherein any two hydrogen atoms on the same carbon atom of the C.sub.3-C.sub.8-carbocycle ring can be replaced by an alkylenedioxy group so that the alkylenedioxy group, when taken together with the carbon atom to which it is attached, forms a 5- to 7-membered heterocycle containing two oxygen atoms wherein the 5- to 7-membered heterocycle containing two oxygen atoms is optionally substituted with from 1 to 3 C.sub.1-C.sub.6alkyl substituents; a 6- to 10-membered bicyclic carbocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6alkoxy, --NH.sub.2, -aminoalkyl, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, alkylcarboxyamido, and --NO.sub.2, wherein any two hydrogen atoms on the same carbon atom of the bicyclic carbocycle rings can be replaced by an oxygen atom to form an oxo (.dbd.O) substituent, and wherein any two hydrogen atoms on the same carbon atom of the bicyclic carbocycle rings can be replaced by an alkylenedioxy group so that the alkylenedioxy group, when taken together with the carbon atom to which it is attached, forms a 5- to 7-membered heterocycle containing two oxygen atoms; a 4- to 7-membered monocyclic heterocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, heterocyclylalkyl, arylalkyl, (C.sub.1-C.sub.9heteroaryl)alkyl-, C.sub.1-C.sub.8acyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, S(O).sub.s--C.sub.1-C.sub.6alkyl, --S(O).sub.S-aryl, -alkylcarboxamido, and --NO.sub.2; or a 6- to 10-membered bicyclic heterocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, heterocyclylalkyl, arylalkyl, (C.sub.1-C.sub.9heteroaryl)alkyl-, C.sub.1-C.sub.8acyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; and R.sup.8 is hydrogen; halogen; C.sub.1-C.sub.8acyl; C.sub.1-C.sub.6alkyl; C.sub.2-C.sub.6alkenyl; C.sub.2-C.sub.6alkynyl; C.sub.6-C.sub.14aryl; heterocyclylalkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8acyl, C.sub.6-C.sub.14aryl, heteroaryl, --S(O).sub.2--C.sub.1-C.sub.6alkyl, and C.sub.3-C.sub.8-carbocycle; or heteroaryl; and Ar is phenyl, naphthyl, or a monocyclic or bicyclic ring system having from 5 to 14 ring members, and containing at least one ring nitrogen atom, wherein the phenyl, naphthyl, and monocyclic or bicyclic ring system is optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2.

2. A compound of claim 1 of the Formula (Ib): ##STR00079## or pharmaceutically acceptable salts thereof, wherein: wherein one of R.sup.30 and R.sup.32, R.sup.30 and R.sup.33, or R.sup.31 and R.sup.32 together are --CH.sub.2--, --CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2--O--, --CH.sub.2CH.sub.2--O--, --CH.sub.2OCH.sub.2--, --CH.sub.2--NH--, --CH.sub.2CH.sub.2--NH--, --CH.sub.2NHCH.sub.2--, --CH.sub.2--N(CH.sub.3)--, --CH.sub.2CH.sub.2--N(CH.sub.3)--, or --CH.sub.2N(CH.sub.3)CH.sub.2--, and with the two carbon atoms to which they are attached form a bridged ring; wherein the bridging ring formed by R.sup.30 and R.sup.32, R.sup.30 and R.sup.33, or R.sup.31 and R.sup.32 is optionally substituted with halogen, or hydroxyl; wherein the remaining R.sup.30, R.sup.31, R.sup.32 and R.sup.33 are each independently selected from hydrogen, halogen, hydroxyl, C.sub.1-C.sub.2alkoxy, C(O)NH.sub.2, C(O)NH(C.sub.1-C.sub.2alkyl), C(O)N(C.sub.1-C.sub.2alkyl)(C.sub.1-C.sub.2alkyl), CN, C(O)OH, and C.sub.1-C.sub.4alkoxycarbonyl; wherein the remaining constituent variables are as defined in claim 1.

3. A compound of claim 1 of the Formula (I): ##STR00080## or pharmaceutically acceptable salts thereof, wherein: each R.sup.1 is independently halogen; C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.1-C.sub.6alkoxy optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkenyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --ON, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkynyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; heteroaryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkyl carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; C.sub.1-C.sub.8acyl; C.sub.1-C.sub.8alkoxycarbonyl; C.sub.1-C.sub.8alkylcarboxy; --N--(C.sub.1-C.sub.6)alkylamido; hydroxyl; NR.sup.4R.sup.5; --NHC(O)NR.sup.4R.sup.5; --NHC(O)OR.sup.6; --NH(SO.sub.2)NH--C.sub.1-C.sub.6alkyl; --NH(SO.sub.2)NH--C.sub.6-C.sub.14aryl; --NHC(S)--NH--C.sub.1-C.sub.6alkyl; --N.dbd.C(S--C.sub.1-C.sub.6alkyl)(NH--C.sub.1-C.sub.6alkyl); or --N(H)--C(.dbd.N--(CN))--(O--C.sub.6-C.sub.14aryl); m is 0, 1 or 2; n is 1 or 2; o is 1 or 2; p and q are each independently 0, 1, or 2; with the two provisos that at least one of n and o must be 1; and the sum of p and q must be greater than zero; r is 0 or 1; each R.sup.20 and R.sup.21 is independently selected from halogen, hydroxyl, C.sub.1-C.sub.2alkoxy, NH.sub.2, NH(C.sub.1-C.sub.2alkyl), N(C.sub.1-C.sub.2alkyl)(C.sub.1-C.sub.2alkyl), NHC(O)(C.sub.1-C.sub.2alkyl), N(C.sub.1-C.sub.2alkyl)C(O)(C.sub.1-C.sub.2alkyl), NHC(O)H, C(O)NH.sub.2, C(O)NH(C.sub.1-C.sub.2alkyl), C(O)N(C.sub.1-C.sub.2alkyl)(C.sub.1-C.sub.2alkyl), CN, C(O)OH, and C(O)OC.sub.1-C.sub.2alkyl; each R.sup.4 and R.sup.5 is independently --H; a 4- to 7-membered monocyclic heterocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, heterocyclylalkyl, C.sub.7-C.sub.24arylalkyl, C.sub.1-C.sub.8acyl, C.sub.1-C.sub.8alkoxycarbonyl, C.sub.1-C.sub.8alkylcarboxy, halo, --C.sub.1-C.sub.8haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; heteroaryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -aminoalkyl, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.8alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; --C.sub.3-C.sub.8-carbocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, --C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, and --NO.sub.2, wherein any two hydrogen atoms on the same carbon atom of the carbocyclic ring can be replaced by an oxygen atom to form an oxo (.dbd.O) substituent, and wherein any two hydrogen atoms on the same carbon atom of the carbocyclic ring can be replaced by an alkylenedioxy group so that the alkylenedioxy group, when taken together with the carbon atom to which it is attached, forms a 5- to 7-membered heterocycle containing two oxygen atoms; or C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.8alkyl), --N(C.sub.1-C.sub.8alkyl)(C.sub.1-C.sub.8alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; or R.sup.4 and R.sup.5 when taken together with the nitrogen to which they are attached can form a 3- to 7-membered heterocycle wherein up to two of the carbon atoms of the heterocycle can be independently replaced with --N(R.sup.7)--, --O--, or --S(.dbd.O).sub.s; each s is independently 1 or 2; R.sup.6 is C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.6-carbocycle; or C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; R.sup.7 is hydrogen; C.sub.1-C.sub.8acyl; C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.3-C.sub.8-carbocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, --C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, and --NO.sub.2; C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, -C.sub.1-C.sub.6alkyl carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; heteroaryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; alkylamino; or aminoaryl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, -C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; with the proviso that when m=2, any two adjacent R.sup.1 groups can be taken together with the two carbons to which they are attached to form a 5- to 7-membered aromatic ring wherein up to 2 of the carbon atoms of the fused ring can be replaced with --N.dbd., --N(R.sup.7)--, --O--, or --S(.dbd.O).sub.s; R.sup.2 is hydrogen; halogen; C.sub.1-C.sub.8acyl; C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, -C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkenyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, -C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkynyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkyl carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; or heteroaryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -aminoalkyl, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; R.sup.3 is hydrogen; C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkenyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.2-C.sub.6alkynyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2,

--NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, -C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; C.sub.1-C.sub.8acyl; C.sub.6-C.sub.14aryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkyl carboxyl, --N--(C.sub.1-C6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; heteroaryl optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; C.sub.7-C.sub.24arylalkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; heterocyclylalkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, --NH(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle; hydroxyl(C.sub.1-C.sub.6alkyl)-; alkylcarboxy; alkoxycarbonyl; C.sub.1-C.sub.6 perfluoroalkyl; --S(O).sub.S--C.sub.1-C.sub.6alkyl wherein the C.sub.1-C.sub.6alkyl of --S(O).sub.S--C.sub.1-C.sub.6alkyl is optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, --C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, and --NO.sub.2; --S(O).sub.S-aryl wherein the aryl of --S(O).sub.s-aryl is optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, --C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkyl carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, and --NO.sub.2; a C.sub.3-C.sub.8carbocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, --C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, and --NO.sub.2, wherein any two hydrogen atoms on the same carbon atom of the carbocycle ring can be replaced by an oxygen atom to form an oxo (.dbd.O) substituent, and wherein any two hydrogen atoms on the same carbon atom of the carbocycle ring can be replaced by an alkylenedioxy group so that the alkylenedioxy group, when taken together with the carbon atom to which it is attached, forms a 5- to 7-membered heterocycle containing two oxygen atoms; a 6- to 10-membered bicyclic carbocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, --C.sub.1-C.sub.6alkoxy, --NH.sub.2, -aminoalkyl, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, and --NO.sub.2, wherein any two hydrogen atoms on the same carbon atom of the bicyclic carbocycle rings can be replaced by an oxygen atom to form an oxo (.dbd.O) substituent, and wherein any two hydrogen atoms on the same carbon atom of the bicyclic carbocycle rings can be replaced by an alkylenedioxy group so that the alkylenedioxy group, when taken together with the carbon atom to which it is attached, forms a 5- to 7-membered heterocycle containing two oxygen atoms; a 4- to 7-membered monocyclic heterocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, heterocyclylalkyl, arylalkyl, C.sub.1-C.sub.8acyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; or a 6- to 10-membered bicyclic heterocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, heterocyclylalkyl, arylalkyl, C.sub.1-C.sub.8acyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2; and Ar is phenyl, naphthyl, or a monocyclic or bicyclic ring system having from 5 to 14 ring members, and containing at least one ring nitrogen atom, wherein the phenyl, naphthyl, and monocyclic or bicyclic ring system is optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --C.sub.1-C.sub.6alkylcarboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, -alkylcarboxamido and --NO.sub.2.

4. A compound of claim 3 or pharmaceutically acceptable salts thereof.

5. A compound of claim 1 wherein Ar is phenyl.

6. A compound of claim 1 wherein m is 1.

7. A compound of claim 1 wherein R.sup.1 is --NHC(O)NR.sup.4R.sup.5, --NHC(O)OR.sup.6, --NH(SO.sub.2)NH--(C.sub.1-C.sub.6alkyl) or --NH(SO.sub.2)NH--C.sub.6-C.sub.14aryl.

8. A compound of claim 7 wherein R.sup.1 is --NHC(O)NR.sup.4R.sup.5.

9. A compound of claim 8 wherein R.sup.5 is H.

10. A compound of claim 9 wherein the --NHC(O)NR.sup.4R.sup.5 group is attached to the C4 of the phenyl ring.

11. A compound of claim 1 wherein R.sup.3 is hydrogen.

12. A compound of claim 1 wherein R.sup.3 is C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 substituents independently selected from halogen, --NH.sub.2, -alkylamino, -dialkylamino, --N(C.sub.1-C.sub.3alkyl)C(O)(C.sub.1-C.sub.6alkyl), --NHC(O)(C.sub.1-C.sub.6alkyl), --NHC(O)H, --C(O)NH.sub.2, --C(O)NH(C.sub.1-C.sub.6alkyl), --C(O)N(C.sub.1-C.sub.6alkyl)(C.sub.1-C.sub.6alkyl), --CN, hydroxyl, --C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl, --C(O)OH, --C.sub.1-C.sub.6alkoxycarbonyl, --C(O)C.sub.1-C.sub.6alkyl, C.sub.6-C.sub.14aryl, heteroaryl, and C.sub.3-C.sub.8-carbocycle.

13. A compound of claim 12 wherein R.sup.3 is C.sub.1-C.sub.6alkyl optionally substituted with from 1 to 3 independently selected halogens.

14. A compound of claim 13 wherein R.sup.3 is 2,2,2-trifluoroethyl.

15. A compound of claim 1 wherein R.sup.3 is a 4- to 7-membered monocyclic heterocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, heterocyclylalkyl, arylalkyl, (C.sub.1-C.sub.9heteroaryl)alkyl-, C.sub.1-C.sub.8acyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, S(O).sub.S--C.sub.1-C.sub.6alkyl, --S(O).sub.S-aryl, -alkylcarboxamido, and --NO.sub.2.

16. A compound of claim 15 wherein R.sup.3 is an optionally substituted piperidinyl.

17. A compound of claim 16 wherein R.sup.3 is optionally substituted piperidin-4-yl.

18. A compound of claim 17 wherein the piperidinyl nitrogen is substituted with C.sub.1-C.sub.6alkyl, heterocyclylalkyl, arylalkyl, (C.sub.1-C.sub.9heteroaryl)alkyl-, C.sub.1-C.sub.8acyl, halo, -haloalkyl, hydroxyl, C.sub.1-C.sub.6hydroxyalkyl, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, S(O).sub.S--C.sub.1-C.sub.6alkyl, --S(O).sub.S-aryl, or -alkylcarboxamido.

19. A compound of claim 1 wherein R.sup.3 is C.sub.7-C.sub.14arylalkyl.

20. A compound of claim 1 wherein R.sup.3 is a 4- to 7-membered monocyclic heterocycle containing at least one ring oxygen atom.

21. A compound of claim 1 wherein R.sup.3 is a C.sub.3-C.sub.8-carbocycle optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, --C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, and --NO.sub.2, wherein any two hydrogen atoms on the same carbon atom of the carbocycle ring can be replaced by an oxygen atom to form an oxo (.dbd.O) substituent, and wherein any two hydrogen atoms on the same carbon atom of the carbocycle ring can be replaced by an alkylenedioxy group so that the alkylenedioxy group, when taken together with the carbon atom to which it is attached, forms a 5- to 7-membered heterocycle containing two oxygen atoms.

22. A compound of claim 1 wherein het is selected from 8-oxa-3-azabicyclo[3.2.1]oct-3-yl, 3-oxa-8-azabicyclo[3.2.1]oct-8-yl, and 2-oxa-5-azabicyclo[2.2.1]hept-5-yl.

23. A compound of claim 22 wherein t is 0.

24. A compound of claim 3 wherein n, o, p, and q are each 1.

25. A compound of claim 4 wherein R.sup.3 is a C.sub.3-C.sub.8-carbocycle, which can be optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, --C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COON, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, and --NO.sub.2, wherein any two hydrogen atoms on the same carbon atom of the carbocycle ring can optionally be replaced by an oxygen atom to form an oxo (.dbd.O) substituent, and wherein any two hydrogen atoms on the same carbon atom of the carbocycle ring can be replaced by an alkylenedioxy group so that the alkylenedioxy group, when taken together with the carbon atom to which it is attached, forms a 5- to 7-membered heterocycle containing two oxygen atoms.

26. A compound of claim 25 wherein R.sup.3 is a C.sub.6-carbocycle, wherein two hydrogen atoms on one of the carbon atoms of the carbocycle ring have been replaced by an alkylenedioxy group so that the alkylenedioxy group, when taken together with the carbon atom to which it is attached, forms a 5- to 7-membered heterocycle containing two oxygen atoms.

27. A compound of claim 4 wherein n, o, p, and q are each 1; r is 0; R.sup.3 is a C.sub.5-C.sub.7 carbocycle, which can be optionally substituted with from 1 to 3 substituents independently selected from C.sub.1-C.sub.6alkyl, halo, -haloalkyl, hydroxyl, --C.sub.1-C.sub.6alkoxy, --NH.sub.2, -alkylamino, -dialkylamino, --COOH, --C.sub.1-C.sub.6alkoxycarbonyl, --(C.sub.1-C.sub.6alkyl)carboxyl, --N--(C.sub.1-C.sub.6)alkylamido, --C(O)NH.sub.2, and --NO.sub.2, wherein any two hydrogen atoms on the same carbon atom of the carbocycle ring can optionally be replaced by an oxygen atom to form an oxo (.dbd.O) substituent, and wherein any two hydrogen atoms on the same carbon atom of the carbocycle ring can be replaced by an alkylenedioxy group so that the alkylenedioxy group, when taken together with the carbon atom to which it is attached, forms a 5- to 7-membered heterocycle containing two oxygen atoms; R.sup.1 is --NHC(O)NR.sup.4R.sup.5, --NHC(O)OR.sup.6, --NH(SO.sub.2)NH--C.sub.1-C.sub.6alkyl or --NH(SO.sub.2)NH--C.sub.6-C.sub.14aryl, and Ar is phenyl.

28. A compound of claim 3 wherein n, o, p, and q are each 1; r is 0; R.sup.3 is a C.sub.6-carbocycle, wherein two hydrogen atoms on one of the carbon atoms of the carbocycle ring have been replaced by an alkylenedioxy group so that the alkylenedioxy group, when taken together with the carbon atom to which it is attached, forms a 5- to 7-membered heterocycle containing two oxygen atoms; R.sup.1 is --NHC(O)NR.sup.4R.sup.5 and Ar is phenyl.

29. A compound selected from the group consisting of: 3-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrim- idin-6-yl]phenol; 1-methyl-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluoroet- hyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; methyl{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluoroethyl)-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-ethyl-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluoroeth- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluoroethyl)-1H-p- yrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluoroethyl)-1H-p- yrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluoroethyl)-1H-p- yrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-(2-fluoroethyl)-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-tr- ifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; methyl 4-[6-{4-[(methylcarbamoyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3.2.1]oct-3- -yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; tert-butyl 4-[6-{4-[(methylcarbamoyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3.2.1]oct-3- -yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[6-{4-[(ethylcarbamoyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-- yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[6-(4-{[(2-fluoroethyl)carbamoyl]amino}phenyl)-4-(8-oxa-3-azabicyclo[3.- 2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(phenylcarbamoyl)am- ino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[6-{4-[(cyclopropylcarbamoyl)amino]phenyl}-4-(8-oxa-3-azabicyclo- [3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate- ; methyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(pyridin-3-ylcarba- moyl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxyla- te; methyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(pyridin-4-ylcar- bamoyl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxy- late; 1-ethyl-3-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(pyridin-3-- ylmethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-(2-fluoroethyl)-3-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(pyrid- in-3-ylmethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea- ; 1-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(pyridin-3-ylmethyl)pip- eridin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-phenylurea; 1-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(pyridin-3-ylmethyl)pipe- ridin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-3-ylurea; 1-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(pyridin-3-ylmethyl)pipe- ridin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-4-ylurea; tert-butyl 4-[6-{4-[(ethylcarbamoyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-- yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; tert-butyl 4-[6-(4-{[(2-fluoroethyl)carbamoyl]amino}phenyl)-4-(8-oxa-3-azabicyclo[3.- 2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; tert-butyl 4-[6-{4-[(cyclopropylcarbamoyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3.2.1]- oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; tert-butyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(phenylcarbamoyl)amino]phe- nyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; tert-butyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(pyridin-3-ylcarbamoyl)ami- no]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate. tert-butyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(pyridin-4-ylcarbamoyl)ami- no]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; 1-methyl-3-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(2,2,2-trifluor- oethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-methyl-3-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(pyridin-3-ylme- thyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-ethyl-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-piperidin-4-yl-1H-p- yrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-piperidin-4-yl-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-phenylurea; 4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]aniline; 4-{[1-(1-benzylpiperidin-4-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-p- yrazolo[3,4-d]pyrimidin-6-yl]amino}phenol; ethyl 4-[6-{4-[(ethylcarbamoyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-- yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; ethyl 4-[6-(4-{[(2-fluoroethyl)carbamoyl]amino}phenyl)-4-(8-oxa-3-azabicyclo[3.- 2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; ethyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(phenylcarbamoyl)ami- no]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; ethyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(pyridin-3-ylcarbamo- yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate- ; ethyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(pyridin-4-ylcarbam- oyl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylat- e; ethyl 4-[6-(4-{[(1-methylpiperidin-4-yl)carbamoyl]amino}phenyl)-4-(8-ox- a-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine- -1-carboxylate; ethyl 4-{6-[4-({[1-(tert-butoxycarbonyl)piperidin-4-yl]carbamoyl}amino)phenyl]-- 4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}pip- eridine-1-carboxylate; ethyl 4-{6-[4-({[3-(methylamino)propyl]carbamoyl}amino)phenyl]-4-(8-oxa-3-azabi- cyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidine-1-carbox- ylate; ethyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(1H-pyrazol-5-ylcarbamoyl)- amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-methylurea; 1-ethyl-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3- ,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-(2-fluoroethyl)urea; 1-cyclopropyl-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyra- zolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-(2-hydroxyethyl)urea; 2-hydroxyethyl{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazo- lo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-phenylurea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[3-(methylamino)propyl]urea; 1-methyl-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo- [3,4-d]pyrimidin-6-yl]phenyl}urea; 1-ethyl-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}urea. 1-(2-fluoroethyl)-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyr- azolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(2-hydroxyethyl)-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1- H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-phenylurea; 1-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-pyridin-3-yl urea; 1-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-[2-(dimethylamino)ethyl]-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct- -3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[3-(dimethylamino)propyl]-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; methyl{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-- d]pyrimidin-6-yl]phenyl}carbamate; 3-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrim- idin-6-yl]phenol; 1-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-methyl-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(4-oxocyclohexyl)-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-(4-hydroxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-py- razolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; ethyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(piperidin-4-ylcarbamoyl)a- mino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; isopropyl 4-[6-(4-aminophenyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-p- yrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; isopropyl 4-[6-{4-[(methylcarbamoyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3.2.1]oct-3- -yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; 1-[4-(1-{1-[(6-bromopyridin-3-yl)methyl]piperidin-4-yl}-4-morpholin-4-yl-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl]-3-methylurea; 1-methyl-3-(4-{4-morpholin-4-yl-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-methyl-3-[4-(1-{1-[(2-methylpyridin-3-yl)carbonyl]piperidin-4-yl}-4-mor- pholin-4-yl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl]urea; 1-methyl-3-[4-(1-{1-[(4-methylpyridin-3-yl)carbonyl]piperidin-4-yl}-4-mor- pholin-4-yl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl]urea; 1-methyl-3-(4-{4-morpholin-4-yl-1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-(4-{1-[1-(2-methoxybenzoyl)piperidin-4-yl]-4-morpholin-4-yl-1H-pyrazolo- [3,4-d]pyrimidin-6-yl}phenyl)-3-methylurea; 1-(4-{1-[1-(3-acetylbenzoyl)piperidin-4-yl]-4-morpholin-4-yl-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl}phenyl)-3-methylurea; 1-(2-fluoro-4-{4-morpholin-4-yl-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-3-ylurea; 2-[4-(6-{4-[(methylcarbamoyl)amino]phenyl}-4-morpholin-4-yl-1H-pyrazolo[3- ,4-d]pyrimidin-1-yl)piperidin-1-yl]acetamide; Methyl 4-(6-{4-[(methylcarbamoyl)amino]phenyl}-4-morpholin-4-yl-1H-pyrazolo[3,4-- d]pyrimidin-1-yl)piperidine-1-carboxylate; isopropyl 4-[6-{4-[(ethylcarbamoyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-- yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; isopropyl 4-[6-(4-{[(2-fluoroethyl)carbamoyl]amino}phenyl)-4-(8-oxa-3-azabicyclo[3.- 2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; isopropyl 4-[6-(4-{[(2-hydroxyethyl)carbamoyl]amino}phenyl)-4-(8-oxa-3-az- abicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-car- boxylate; isopropyl 4-[6-{4-[(cyclopropylcarbamoyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3.2.1]- oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; isopropyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(phenylcarbamoyl- )amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; isopropyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(pyridin-3-ylcar- bamoyl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxy- late; isopropyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-{4-[(pyridin-4-ylcarbamoyl)ami- no]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; isopropyl 4-[6-{4-[(methoxycarbonyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3- .2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; 3-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimi- din-6-yl]phenol; 1-ethyl-6-(1H-indol-5-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazo- lo[3,4-d]pyrimidine; 1-{4-[1-benzyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-benzyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-ethylurea; 1-{4-[1-benzyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-pyridin-4-yl urea; 4-[1-(1-isobutyrylpiperidin-4-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1- H-pyrazolo[3,4-d]pyrimidin-6-yl]aniline. 1-{4-[1-(1-isobutyrylpiperidin-4-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl- )-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-ethyl-3-{4-[1-(1-isobutyrylpiperidin-4-yl)-4-(8-oxa-3-azabicyclo[3.2.1]- oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(2-hydroxyethyl)-3-{4-[1-(1-isobutyrylpiperidin-4-yl)-4-(8-oxa-3-azabic- yclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(2-fluoroethyl)-3-{4-[1-(1-isobutyrylpiperidin-4-yl)-4-(8-oxa-3-azabicy- clo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[1-(1-isobutyrylpiperidin-4-yl)-4-(8-oxa-3-azabicyclo[- 3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-(1-isobutyrylpiperidin-4-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl- )-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-phenylurea; 1-{4-[1-(1-isobutyrylpiperidin-4-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl- )-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-{4-[1-(1-isobutyrylpiperidin-4-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl- )-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6- -yl]phenyl}-3-pyridin-3-ylurea; 1-(4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(1,4-dioxaspiro[4.5]decan- -8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-methylurea; 1-(4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(4-oxocyclohexyl)-1H-pyra- zolo[3,4-d]pyrimidin-6-yl)phenyl)-3-methylurea; 1-(4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(4-hydroxycyclohexyl)-1H-- pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-methylurea; 1-(4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-((1r,4r)-4-hydroxycyclohe- xyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-methylurea; and 1-(4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-((1s,4s)-4-hydroxycyclohe- xyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-methylurea; and 2-hydroxyethyl{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluor- oethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate.

30. A compound selected from the group consisting of: methyl 4-[6-{4-[(ethoxycarbonyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-- yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[6-(4-{[(2-hydroxyethoxy)carbonyl]amino}phenyl)-4-(8-oxa-3-azabicyclo[3- .2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[6-(4-{[(2-methoxyethoxy)carbonyl]amino}phenyl)-4-(8-oxa-3-azabi- cyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbox- ylate; methyl 4-[6-(4-{[(2-aminoethoxy)carbonyl]amino}phenyl)-4-(8-oxa-3-azabicyclo[3.2- .1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-{6-[4-({[2-(dimethylamino)ethoxy]carbonyl}amino)phenyl]-4-(8-oxa- -3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidine-- 1-carboxylate; methyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-6-(4-{[(2-pyrrolidin-1-ylethoxy)- carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbo- xylate; methyl 4-[6-(4-{[(2-morpholin-4-ylethoxy)carbonyl]amino}phenyl)-4-(8-oxa-3-azabi- cyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbox- ylate; methyl 4-{6-[4-({[2-(4-methylpiperazin-1-yl)ethoxy]carbonyl}amino)phenyl]-4-(8-o- xa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidin- e-1-carboxylate; methyl 4-[6-{4-[(methoxycarbonyl)amino]phenyl}-4-(8-oxa-3-azabicyclo[3.2.1]oct-3- -yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[6-(4-aminophenyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,- 4-d]pyrimidin-1-yl]piperidine-1-carboxylate; 2-hydroxyethyl{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3- .2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 3-hydroxypropyl{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[- 3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-ethylurea; 1-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-(2-fluoroethyl)urea; 1-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-(2-hydroxyethyl)urea; 1-cyclopropyl-3-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo- [3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-phenylurea; 1-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 2,2,2-trifluoroethyl{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabic- yclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 2-fluoroethyl{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.- 2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 3-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-1,3-oxazolidin-2-one; 2-({4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}amino)ethanol; 1-[2-(dimethylamino)ethyl]-3-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa- -3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea- ; 1-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-[2-(4-methylpiperazin-1-yl)- ethyl]urea; 1-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)p- henyl]urea; methyl{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(4-oxocyclohexyl)-1H-py- razolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; methyl{4-[1-(4-hydroxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1- H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; methyl{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3- ,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d- ]pyrimidin-6-yl]phenyl}-3-methylurea; 1-ethyl-3-{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazo- lo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(2-fluoroethyl)-3-{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)- -1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-- pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(2-hydroxyethyl)-3-{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl- )-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 2-hydroxyethyl{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-py- razolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 3-hydroxypropyl{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-p- yrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 2,3-dihydroxypropyl{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d- ]pyrimidin-6-yl]phenyl}-3-phenylurea; 1-{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d- ]pyrimidin-6-yl]phenyl}-3-pyridin-3-yl urea; 1-{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d- ]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-{4-[1-(4,4-dimethoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1- H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-(1,5-dioxaspiro[5.5]undec-9-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3- -yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-(3,3-dimethyl-1,5-dioxaspiro[5.5]undec-9-yl)-4-(8-oxa-3-azabicycl- o[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-(4-{1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-methylurea; methyl (4-{1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-p- yrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate; 1-(4-{1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-[4-(2-hydroxyethyl)phenyl]urea; 1-(4-{1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-phenylurea; 1-(4-{1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-3-ylurea; 2-hydroxyethyl(4-{1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]- oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate; 1-(4-{1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-[4-(4-methylpiperazin-1-yl)phenyl- ]urea; 1-(4-{1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-ethylurea; 1-cyclopropyl-3-(4-{1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.- 1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-(4-{1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-4-ylurea; 1-(4-{1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-[4-(hydroxymethyl)phenyl]urea; methyl 4-{6-[4-({[4-(hydroxymethyl)phenyl]carbamoyl}amino)phenyl]-4-(8-ox- a-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidine- -1-carboxylate; methyl 4-{6-[4-({[4-(2-hydroxyethyl)phenyl]carbamoyl}amino)phenyl]-4-(8-oxa-3-az- abicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidine-1-car- boxylate; methyl 4-{6-[4-({[4-(4-methylpiperazin-1-yl)phenyl]carbamoyl}amino)phenyl]-4-(8-- oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidi- ne-1-carboxylate; methyl 4-{6-[4-({[6-(4-methylpiperazin-1-yl)pyridin-3-yl]carbamoyl}amino)phenyl]- -4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}pi- peridine-1-carboxylate; methyl 4-[6-(4-{[(2-aminoethyl)carbamoyl]amino}phenyl)-4-(8-oxa-3-azabicyclo[3.2- .1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-{6-[4-({[2-(dimethylamino)ethyl]carbamoyl}amino)phenyl]-4-(8-oxa- -3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidine-- 1-carboxylate; methyl 4-{6-[4-({[2-(4-methylpiperazin-1-yl)ethyl]carbamoyl}amino)phenyl]-4-(8-o- xa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidin- e-1-carboxylate; methyl 4-{6-[4-({[3-(hydroxymethyl)phenyl]carbamoyl}amino)phenyl]-4-(8-oxa-3-aza- bicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidine-1-carb- oxylate; methyl 4-{6-[4-({[2-(hydroxymethyl)phenyl]carbamoyl}amino)phenyl]-4-(8-oxa-3-aza- bicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidine-1-carb- oxylate; 1-(2-aminoethyl)-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[2-(methylamino)ethyl]urea; 1-[2-(dimethylamino)ethyl]-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-- 3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(3-aminopropyl)-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-- pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[3-(dimethylamino)propyl]-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct- -3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[2-(4-methylpiperazin-1-yl)ethyl]urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-(2-morpholin-4-ylethyl)urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phenyl]urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-(4-morpholin-4-ylphenyl)urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[4-(hydroxymethyl)phenyl]urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[4-(2-hydroxyethyl)phenyl]urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-(6-morpholin-4-ylpyridin-3-yl)urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]urea; 1-{4-[2-(dimethylamino)ethoxy]phenyl}-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo- [3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-(4-methoxyphenyl)urea; 1-(4-chlorophenyl)-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-(4-methylphenyl)urea; 1-(4-cyanophenyl)-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-- pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 2-hydroxypropyl{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyraz- olo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; methyl{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyr- azolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazol- o[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-ethyl-3-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 2-hydroxyethyl{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl- )-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-(2-hydroxyethyl)-3-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]o- ct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazol- o[3,4-d]pyrimidin-6-yl]phenyl}-3-phenylurea; 1-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazol- o[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazol- o[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazol- o[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(hydroxymethyl)phenyl]urea; 1-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazol- o[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(2-hydroxyethyl)phenyl]urea; 1-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazol- o[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phenyl]urea; 1-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazol- o[3,4-d]pyrimidin-6-yl]phenyl}-3-(4-morpholin-4-ylphenyl)urea; 1-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazol- o[3,4-d]pyrimidin-6-yl]phenyl}-3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]u- rea; 1-{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyr- azolo[3,4-d]pyrimidin-6-yl]phenyl}-3-(6-morpholin-4-ylpyridin-3-yl)urea; 2-[6-(4-aminophenyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,- 4-d]pyrimidin-1-yl]ethanol; ethyl{4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyra- zolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 2-hydroxyethyl(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(2,2,2-trifl- uoroethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamat- e; 2-hydroxyethyl(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(pyridin-3- -ylmethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamat- e; 2-hydroxyethyl{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(4-oxocyclohe- xyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 2-hydroxyethyl{4-[1-(4-hydroxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct- -3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 2-hydroxyethyl{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-cyclopropylurea; 1-{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(hydroxymethyl)phenyl]urea; 1-{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(2-hydroxyethyl)phenyl]urea; 1-{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phenyl]urea; 1-{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-(4-morpholin-4-ylphenyl)urea; 1-{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]ure- a; 1-{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazol- o[3,4-d]pyrimidin-6-yl]phenyl}-3-(6-morpholin-4-ylpyridin-3-yl)urea; 1-{4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-{4-[2-(dimethylamino)ethoxy]phenyl}urea; 1-[2-(2-aminoethoxy)ethyl]-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-- 3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[(1-methylpiperidin-4-yl)methyl]urea; 1-cyclohexyl-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyraz- olo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-(1-methylpiperidin-4-yl)urea;

1-(cis-4-aminocyclohexyl)-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3- -yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(trans-4-aminocyclohexyl)-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct- -3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[4-(hydroxymethyl)phenyl]-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[4-(2-hydroxyethyl)phenyl]-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]o- ct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[4-(dimethylamino)phenyl]-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(4-aminophenyl)-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]urea; 1-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phenyl]urea; 1-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-(6-morpholin-4-ylpyridin-3-yl)urea; 1-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-(4-morpholin-4-ylphenyl)urea; 1-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-[4-(methylsulfonyl)phenyl]urea; 1-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]py- rimidin-6-yl]phenyl}-3-{4-[(2-piperidin-1-ylethyl)sulfonyl]phenyl}urea; 1-{4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo- [3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-[4-(dimethylamino)phenyl]-3-{4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo- [3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[2-(dimethylamino)ethoxy]phenyl}-3-{4-[1-(2-fluoroethyl)-4-(8-oxa-3-- azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo- [3,4-d]pyrimidin-6-yl]phenyl}-3-(4-morpholin-4-ylphenyl)urea; 2-hydroxyethyl{4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)- -1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-{4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo- [3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phenyl]urea; 1-ethyl-3-{4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-- pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo- [3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-{4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo- [3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(hydroxymethyl)phenyl]urea; 1-(4-morpholin-4-ylphenyl)-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-- (2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(6-morpholin-4-ylpyridin-3-yl)-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-- yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[4-(hydroxymethyl)phenyl]-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1- -(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 3-aminobenzyl{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluoro- ethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-[3-(hydroxymethyl)phenyl]-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1- -(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 3-(dimethylamino)phenyl{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2- -trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-[3-(dimethylamino)phenyl]-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1- -(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; N.about.2.about.,N.about.2.about.-dimethyl-N-{4-[({4-[1-methyl-4-(8-oxa-3- -azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbam- oyl)amino]phenyl}glycinamide; N-{4-[({4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4- -d]pyrimidin-6-yl]phenyl}carbamoyl)amino]phenyl}acetamide; 1-[4-(2-hydroxyethyl)phenyl]-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-- 1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}u- rea; 1-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-3-{4-[4-(8-oxa-3-azabicycl- o[3.2.1]oct-3-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-y- l]phenyl}urea; 1-[4-(2-hydroxyethoxy)phenyl]-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)- -1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 2-hydroxyethyl{4-[1-(1-benzylpiperidin-4-yl)-4-(8-oxa-3-azabicyclo[3.2.1]- oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-cyclopropyl-3-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(2,2,2-tri- fluoroethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 2-hydroxyethyl{4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1-(2,2,2-trifluor- oethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-methyl-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1-(2,2,2-trifluoroet- hyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1-(2,2,2-trifluoroethyl)-1H-p- yrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-[4-(hydroxymethyl)phenyl]-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1- -(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oc- t-8-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}u- rea; 1-cyclopropyl-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1-(2,2,2-tr- ifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[4-(2-hydroxyethyl)phenyl]-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-- 1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(4-morpholin-4-ylphenyl)-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1-- (2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(6-morpholin-4-ylpyridin-3-yl)-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-- yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[2-(dimethylamino)ethoxy]phenyl}-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]o- ct-8-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}- urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-- d]pyrimidin-6-yl]phenyl}-3-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[3-(4-methylpiperazin-1-yl)-3-oxopropyl]urea; N-[2-(dimethylamino)ethyl]-N.about.2.about.-({4-[1-ethyl-4-(8-oxa-3-azabi- cyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamoyl)gl- ycinamide; N-[2-(dimethylamino)ethyl]-N.about.3.about.-({4-[1-ethyl-4-(8-o- xa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}ca- rbamoyl)-beta-alaninamide; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-(4-pyrrolidin-1-ylphenyl)urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[4-(2-hydroxyethoxy)phenyl]urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[6-(2-hydroxyethoxy)pyridin-3-yl]urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[6-(2-morpholin-4-ylethoxy)pyridin-3-yl]urea; 1-[6-(dimethylamino)pyridin-3-yl]-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2- .1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 4-[({4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]p- yrimidin-6-yl]phenyl}carbamoyl)amino]benzamide; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[6-(methylamino)pyridin-3-yl]urea; 1-(6-aminopyridin-3-yl)-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-(4-piperazin-1-ylphenyl)urea; 1-{4-[(2,2-dimethylhydrazino)carbonyl]phenyl}-3-{4-[1-ethyl-4-(8-oxa-3-az- abicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 4-[({4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]p- yrimidin-6-yl]phenyl}carbamoyl)amino]-N-pyrrolidin-1-ylbenzamide; 2-hydroxyethyl(4-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(2,2,2- -trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate; 1-methyl-3-(4-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(2,2,2-tr- ifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-(4-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(2,2,2-trifluoroet- hyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-3-ylurea; 1-[4-(hydroxymethyl)phenyl]-3-(4-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hep- t-5-yl]-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)u- rea; 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-(4-{4-[(1S,4S)-2-oxa-5-azabicy- clo[2.2.1]hept-5-yl]-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-- 6-yl}phenyl)urea; 1-cyclopropyl-3-(4-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(2,2- ,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-[4-(2-hydroxyethyl)phenyl]-3-(4-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]he- pt-5-yl]-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)- urea; 1-(4-morpholin-4-ylphenyl)-3-(4-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1- ]hept-5-yl]-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phen- yl)urea; 1-(6-morpholin-4-ylpyridin-3-yl)-3-(4-{4-[(1S,4S)-2-oxa-5-azabicy- clo[2.2.1]hept-5-yl]-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-- 6-yl}phenyl)urea; 1-{4-[2-(dimethylamino)ethoxy]phenyl}-3-(4-{4-[(1S,4S)-2-oxa-5-azabicyclo- [2.2.1]hept-5-yl]-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-y- l}phenyl)urea; 1-ethyl-3-{4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]o- ct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-py- razolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-{4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-py- razolo[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phenyl]ur- ea; 1-{4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-(4-piperazin-1-ylphenyl)urea; 4-[({4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-- pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamoyl)amino]benzamide; 4-[({4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-- pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamoyl)amino]-N-pyrrolidin-1-ylben- zamide; 1-[4-(hydroxymethyl)phenyl]-3-{4-[1-(4-methoxycyclohexyl)-4-(8-oxa- -3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea- ; 1-{4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-p- yrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-[6-(4-methylpiperazin-1-yl)pyridin-- 3-yl]urea; 1-{4-[2-(dimethylamino)ethoxy]phenyl}-3-{4-[1-(4-methoxycyclohe- xyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-y- l]phenyl}urea; 2-hydroxyethyl{4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct- -3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[(5r,8r)-1-oxaspiro[4.5]dec- -8-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-4-ylurea; 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1-[(5r,8r)-1-oxaspiro[4.5]dec-8-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-- yl}phenyl)urea; 1-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[(5r,8r)-1-oxaspiro[4.5]dec- -8-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-(4-piperazin-1-ylphenyl)- urea; 2-hydroxyethyl(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[(5r,8r)-1- -oxaspiro[4.5]dec-8-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate; 1-cyclopropyl-3-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[(5r,8r)-1-ox- aspiro[4.5]dec-8-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluoroethyl)-1H-p- yrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-(4-piperazin-1-ylphenyl)urea; 1-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1-(2,2,2-trifluoroethyl)-1H-p- yrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-(4-piperazin-1-ylphenyl)urea; 1-(4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-methylurea; 1-ethyl-3-(4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-azabicyclo[- 3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-cyclopropyl-3-(4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-azabi- cyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-(2-hydroxyethyl)-3-(4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-- azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 2-hydroxyethyl(4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-azabicy- clo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate; 1-(4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-phenylurea; 1-(4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-4-ylurea; 1-(4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-3-ylurea; 1-(4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-[4-(4-methylpiperazin-1- -yl)phenyl]urea; methyl (4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-- 3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate; 1-methyl-3-(4-{1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa-3-azabic- yclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-(4-{1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa-3-azabicyclo[3.2.- 1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-3-ylurea; 1-methyl-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(4-pyrrolidin-1-yl- cyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(4-pyrrolidin-1-ylcyclohexy- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-(4-{1-[4-(2,2-dimethylhydrazino)cyclohexyl]-4-(8-oxa-3-azabicyclo[3.2.1- ]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-methylurea; 1-{4-[1-{4-[(2-hydroxyethyl)amino]cyclohexyl}-4-(8-oxa-3-azabicyclo[3.2.1- ]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-(4-{1-[2-methoxy-1-(methoxymethyl)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-(4-piperazin-1-ylphenyl- )urea; 1-{4-[(2,2-dimethylhydrazino)carbonyl]phenyl}-3-(4-{1-[2-methoxy-1-- (methoxymethyl)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,- 4-d]pyrimidin-6-yl}phenyl)urea; 1-{4-[4-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)-1-(2,2,2-trifluoroethyl)-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-{4-[4-(7-formyl-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)-1-(2,2,2-trifluo- roethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-{4-[4-(7-acetyl-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)-1-(2,2,2-trifluo- roethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea; tert-butyl 7-[6-{4-[(pyridin-4-ylcarbamoyl)amino]phenyl}-1-(2,2,2-trifluoroethyl)-1H- -pyrazolo[3,4-d]pyrimidin-4-yl]-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carb- oxylate; 1-methyl-3-(4-{4-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(- 2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-cyclopropyl-3-(4-{4-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(2,2- ,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 2-hydroxyethyl(4-{4-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(2,2,2- -trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate; 1-(4-{4-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(2,2,2-trifluoroet- hyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-3-ylurea; 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-(4-{4-[(1R,4R)-2-oxa-5-azabicyclo[- 2.2.1]hept-5-yl]-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl- }phenyl)urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-3-pyrrolidin-1-yl-1H-- pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-3-pyrrolidin-1-yl-1H-- pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-ethyl-3-(4-methylpiperazin-1-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct--

3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-3-pyridin-3-yl-1H-pyr- azolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-3-vinyl-1H-pyrazolo[3- ,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[3-(1,2-dihydroxyethyl)-1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl- )-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-ethyl-3-formyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[- 3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-(4-{1-ethyl-3-[(4-methylpiperazin-1-yl)methyl]-4-(8-oxa-3-azabicyclo[3.- 2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-methylurea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-3-(pyrrolidin-1-ylmet- hyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; methyl 4-[6-(4-{[(2-hydroxyethoxy)carbonyl]amino}phenyl)-4-(3-oxa-8-azabicyclo[3- .2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[6-{4-[(methylcarbamoyl)amino]phenyl}-4-(3-oxa-8-azabicyclo[3.2.- 1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[6-{4-[(ethylcarbamoyl)amino]phenyl}-4-(3-oxa-8-azabicyclo[3.2.1- ]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[6-(4-{[(2-fluoroethyl)carbamoyl]amino}phenyl)-4-(3-oxa-8-azabic- yclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxy- late; methyl 4-[6-{4-[(cyclopropylcarbamoyl)amino]phenyl}-4-(3-oxa-8-azabicyclo[3.2.1]- oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-6-{4-[(phenylcarbamoyl)am- ino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate; methyl 4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-6-{4-[(pyridin-3-ylcarbam- oyl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylat- e; methyl 4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-6-{4-[(pyridin-4-ylcarb- amoyl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxyl- ate; methyl 4-{6-[4-({[4-(4-methylpiperazin-1-yl)phenyl]carbamoyl}amino)phenyl]-4-(3-- oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidi- ne-1-carboxylate; methyl 4-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-6-(4-{[(4-piperazin-1-ylphenyl)c- arbamoyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbo- xylate; methyl 4-{6-[4-({[6-(4-methylpiperazin-1-yl)pyridin-3-yl]carbamoyl}amino)phenyl]- -4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl}pi- peridine-1-carboxylate; methyl 4-[6-{4-[({4-[(dimethylamino)methyl]phenyl}carbamoyl)amino]phenyl}-4-(3-o- xa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin- e-1-carboxylate; methyl 4-[6-{4-[({4-[(4-methylpiperazin-1-yl)methyl]phenyl}carbamoyl)amino]pheny- l}-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]- piperidine-1-carboxylate; methyl 4-[6-{4-[({4-[2-(dimethylamino)ethoxy]phenyl}carbamoyl)amino]phenyl}-4-(3- -oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperid- ine-1-carboxylate; 2-hydroxyethyl(4-{1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa-3-aza- bicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate; 1-ethyl-3-(4-{1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa-3-azabicy- clo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-(2-fluoroethyl)-3-(4-{1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa- -3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea- ; 1-cyclopropyl-3-(4-{1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa-3-- azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-(4-{1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa-3-azabicyclo[3.2.- 1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-phenylurea; 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluoroethyl)-1H-pyra- zolo[3,4-d]pyrimidin-6-yl]aniline; methyl{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d- ]pyrimidin-6-yl]phenyl}carbamate; 1-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-3-ylurea; methyl{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct- -3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 3-[4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrim- idin-6-yl]phenol; 2-hydroxyethyl(4-{4-[(6R)-6-hydroxy-8-oxa-3-azabicyclo[3.2.1]oct-3-yl]-1-- (2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)carbamate; 1-{4-[1-(trans-4-hydroxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)- -1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-(cis-4-hydroxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1- H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 3-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-phenyl-1H-pyrazolo[3,- 4-d]pyrimidin-6-yl}phenol; 1-{4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-py- razolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-py- razolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-{4-[1-(1,3-dioxan-5-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazo- lo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-(trans-4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)- -1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[1-(cis-4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1- H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-(1,4-dioxaspiro[4.5]dec-8-yl)-6-(1H-indol-5-yl)-4-(8-oxa-3-azabicyclo[3- .2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidine; 1-methyl-3-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[(5r,8r)-1-oxaspir- o[4.5]dec-8-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea; 1-{4-[4-(6-hydroxy-3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1-(2,2,2-trifluoroe- thyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-{4-[4-(6,8-dioxa-3-azabicyclo[3.2.1]oct-3-yl)-1-methyl-1H-pyrazolo[3,4-- d]pyrimidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-{4-[4-(6,8-dioxa-3-azabicyclo[3.2.1]oct-3-yl)-1-methyl-1H-pyrazolo[3,4-- d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-(4-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(2,2,2-trifluoroet- hyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-(4-piperazin-1-ylphenyl)ur- ea; 6-(1H-indol-5-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(pyridin-- 3-ylmethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidine; 1-cyclopropyl-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-triflu- oroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-(trans-4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)- -1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phe- nyl]urea; 1-{4-[3-bromo-1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-p- yrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea; 1-cyclopropyl-3-{4-[1-(cis-4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2- .1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[1-(trans-4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3- .2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1-(4-oxocyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(4-oxocyclohe- xyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[1-(cis-4-hydroxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2- .1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[1-(trans-4-hydroxycyclohexyl)-4-(8-oxa-3-azabicyclo[3- .2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-(trans-4-hydroxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)- -1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phe- nyl]urea; and 1-{4-[1-(cis-4-hydroxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1- H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)pheny- l]urea.

31. A compound selected from the group consisting of: 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-{4-[(4-methylpiperazin-1-yl)methyl]phenyl}urea; 1-[4-(aminomethyl)phenyl]-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3- -yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[4-(pyrrolidin-1-ylmethyl)phenyl]urea; 1-{4-[(dimethylamino)methyl]phenyl}-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3- .2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[1-(4-ethoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(4-propoxycyc- lohexyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1-(4-propoxycyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}ur- ea; 1-{4-[1-(4-ethoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-- pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phenyl]- urea; 1-cyclobutyl-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-- pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-methylurea; 1-cyclopentyl-3-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyra- zolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-ethyl-3-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3- ,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-phenylurea; tert-butyl 9-(6-(4-((2-hydroxyethoxy)carbonylamino)phenyl)-1-(2,2,2-trifluoroethyl)-- 1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-ca- rboxylate; 2-hydroxyethyl 4-(4-(3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl)-1- H-pyrazolo[3,4-d]pyrimidin-6-yl)phenylcarbamate; 1-(4-{[2-(dimethylamino)ethyl](methyl)amino}phenyl)-3-{4-[1-ethyl-4-(8-ox- a-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}ure- a; 2-hydroxyethyl{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyra- zolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate; 1-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-{4-[(4-methylpiperazin-1-yl)methyl]phenyl}urea; 1-(4-(4-(3,7-dioxa-9-azabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl- )-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-methylurea; 1-{4-[1-(cis-4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1- H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)pheny- l]urea; 1-cyclopentyl-3-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(4-(4-(3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl- )-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-(4-(2-(dimethylamino)ethoxy)p- henyl)urea; 1-(4-(4-(3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl- )-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-methylurea; 1-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[4-(pyrrolidin-1-ylmethyl)phenyl]urea; 1-(4-(4-(3-oxa-9-azabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-methylurea; 1-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-pyridin-3-ylurea; 1-{4-[2-(dimethylamino)ethoxy]phenyl}-3-{4-[1-ethyl-4-(3-oxa-8-azabicyclo- [3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-(4-{[2-(dimethylamino)ethyl](methyl)amino}phenyl)-3-{4-[1-ethyl-4-(3-ox- a-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}ure- a; 1-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]p- yrimidin-6-yl]phenyl}-3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]urea; 2-hydroxyethyl 4-(4-(2-oxa-5-azabicyclo[2.2.2]octan-5-yl)-1-(2,2,2-trifluoroethyl)-1H-py- razolo[3,4-d]pyrimidin-6-yl)phenylcarbamate; 2-hydroxyethyl 4-(4-(3-oxa-9-azabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl)-1H-py- razolo[3,4-d]pyrimidin-6-yl)phenylcarbamate; 1-(4-{[2-(dimethylamino)ethyl]amino}phenyl)-3-{4-[1-ethyl-4-(3-oxa-8-azab- icyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[(dimethylamino)methyl]phenyl}-3-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3- .2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-cyclopropyl-3-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyra- zolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 2-hydroxyethyl 4-(4-(3,7-dioxa-9-azabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl)-1- H-pyrazolo[3,4-d]pyrimidin-6-yl)phenylcarbamate; tert-butyl 9-(6-(4-(3-methylureido)phenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-- d]pyrimidin-4-yl)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylate; 1-(4-(4-(2-oxa-5-azabicyclo[2.2.2]octan-5-yl)-1-(2,2,2-trifluoroethyl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-methylurea; 1-(4-{[2-(dimethylamino)ethyl]amino}phenyl)-3-{4-[1-ethyl-4-(8-oxa-3-azab- icyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[4-(2-pyrrolidin-1-ylethoxy)phenyl]urea; 1-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phenyl]urea; 1-cyclobutyl-3-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyraz- olo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-[4-(aminomethyl)phenyl]-3-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8- -yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea; 1-{4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1H-pyrazolo[3,4-d]pyr- imidin-6-yl]phenyl}-3-pyridin-4-ylurea; 1-(4-(4-(3-oxa-9-azabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl)-1H- -pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-(4-(2-(dimethylamino)ethoxy)pheny- l)urea; 1-(4-(4-(2-oxa-5-azabicyclo[2.2.2]octan-5-yl)-1-(2,2,2-trifluoroet- hyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-(4-(2-(dimethylamino)ethox- y)phenyl)urea; 1-(4-(4-(3,7-dioxa-9-azabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl- )-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenyl)-3-(4-(2-(dimethylamino)ethoxy)p- henyl)urea; and tert-butyl 9-(6-(4-(3-(4-(2-(dimethylamino)ethoxy)phenyl)ureido)phenyl)-1-(2,2,2-tri- fluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-oxa-7,9-diazabicyclo[3.3.- 1]nonane-7-carboxylate.

32. The compound 1-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea.

33. The compound 1-{4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-y- l)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)p- henyl]urea.

34. The compound 1-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[(5r,8r)-1-oxaspiro[4.5]dec- -8-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-4-ylurea.

35. The compound 1-cyclopropyl-3-(4-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-(2,2- ,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea.

36. The compound 1-{4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo- [3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phenyl]urea.

37. The compound 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oc- t-3-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}u- rea.

38. The compound 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]oc- t-8-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}u- rea.

39. The compound 1-{4-[2-(dimethylamino)ethoxy]phenyl}-3-{4-[4-(3-oxa-8-azabicyclo[3.2.1]o- ct-8-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}- urea.

40. The compound 2-hydroxyethyl{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluor- oethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate.

41. The compound 1-{4-[1-(trans-4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)- -1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-[4-(4-methylpiperazin-1-yl)phe- nyl]urea.

42. The compound 1-cyclopropyl-3-{4-[1-(trans-4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3- .2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea.

43. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

44. The composition of claim 43, wherein the pharmaceutically acceptable carrier suitable for oral administration and the composition comprises an oral dosage form.

45. A composition comprising a compound of claim 1; a second compound selected from the group consisting of a topoisomerase I inhibitor, procarbazine, dacarbazine, gemcitabine, capecitabine, methotrexate, taxol, taxotere, mercaptopurine, thioguanine, hydroxyurea, cytarabine, cyclophosphamide, ifosfamide, nitrosoureas, cisplatin, carboplatin, mitomycin, dacarbazine, procarbizine, etoposide, teniposide, campathecins, bleomycin, doxorubicin, idarubicin, daunorubicin, dactinomycin, plicamycin, mitoxantrone, L-asparaginase, doxorubicin, epirubicin, 5-fluorouracil, docetaxel, paclitaxel, leucovorin, levamisole, irinotecan, estramustine, etoposide, nitrogen mustards, bis-chloroethylnitrosourea, carmustine, lomustine, vinblastine, vincristine, vinorelbine, cisplatin, carboplatin, oxaliplatin, imatinib mesylate, Avastin (bevacizumab), hexamethylmelamine, topotecan, tyrosine kinase inhibitors, tyrphostins, herbimycin A, genistein, erbstatin, lavendustin A, hydroxyzine, glatiramer acetate, interferon beta-1a, interferon beta-1b, natalizumab and lavendustin A; and a pharmaceutically acceptable carrier.

46. The composition of claim 45, wherein the second compound is bevacizumab.

Details for Patent 8,129,371

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Recordati Rare Diseases, Inc. ELSPAR asparaginase For Injection 101063 01/10/1978 ⤷  Try a Trial 2027-10-16
Bayer Healthcare Pharmaceuticals Inc. BETASERON interferon beta-1b For Injection 103471 07/23/1993 ⤷  Try a Trial 2027-10-16
Biogen Inc. AVONEX interferon beta-1a For Injection 103628 05/17/1996 ⤷  Try a Trial 2027-10-16
Biogen Inc. AVONEX interferon beta-1a Injection 103628 05/28/2003 ⤷  Try a Trial 2027-10-16
Biogen Inc. AVONEX interferon beta-1a Injection 103628 02/27/2012 ⤷  Try a Trial 2027-10-16
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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