Details for Patent: 7,915,250

Title:	Azetidines as MEK inhibitors for the treatment of proliferative diseases
Abstract:	Disclosed are compounds of Formula (I) and pharmaceutically acceptable salts and solvates thereof. Such compounds are MEK inhibitors and are useful in the treatment of proliferative diseases, such as cancer. Also disclosed are pharmaceutical compositions containing such compounds as well as methods of using the compounds and compositions of the invention in the treatment of cancer.
Inventor(s):	Aay; Naing (San Mateo, CA), Anand; Neel Kumar (Burlingame, CA), Blazey; Charles M. (San Francisco, CA), Bowles; Owen Joseph (Pacifica, CA), Bussenius; Joerg (Foster City, CA), Costanzo; Simona (Los Altos, CA), Curtis; Jeffry Kimo (San Anselmo, CA), DeFina; Steven Charles (Burlingame, CA), Dubenko; Larisa (San Francisco, CA), Joshi; Anagha Abhijit (Fremont, CA), Kennedy; Abigail R. (Oakland, CA), Kim; Angie Inyoung (San Mateo, CA), Koltun; Elena S. (Foster City, CA), Manalo; Jean-Claire Limun (Daly City, CA), Peto; Csaba J. (Alameda, CA), Rice; Kenneth D. (San Rafael, CA), Tsang; Tsze H. (El Cerrito, CA)
Assignee:	Exelixis, Inc. (South San Francisco, CA)
Filing Date:	May 05, 2010
Application Number:	12/774,544
Claims:	1. A compound of formula I: ##STR00473## or a pharmaceutically acceptable salt thereof, wherein A, X, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are as defined in Group B, Group C, or Group D: Group B: A is heteroarylene optionally substituted with one, two, three, or four groups selected from R.sup.10, R.sup.12, R.sup.14, R.sup.16 and R.sup.19 where R.sup.10, R.sup.12, R.sup.14 and R.sup.16 are independently hydrogen, alkyl, alkenyl, alkynyl, halo, haloalkoxy, hydroxy, alkoxy, cyano, amino, alkylamino, dialkylamino, haloalkyl, alkylsulfonylamino, alkylcarbonyl, alkenylcarbonyl, alkoxycarbonyl, alkenyloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, or alkylcarbonylamino; where R.sup.19 is hydrogen, alkyl, or alkenyl; and where each alkyl and alkenyl, either alone or as part of another group within R.sup.10, R.sup.12, R.sup.14, R.sup.16, and R.sup.19, is independently optionally substituted with halo, hydroxy, or alkoxy; X is alkyl, halo, haloalkyl, or haloalkoxy; R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently hydrogen, halo, nitro, --NR.sup.8R.sup.8', --OR.sup.8, --NHS(O).sub.2R.sup.8, --CN, --S(O).sub.mR.sup.8, --S(O).sub.2NR.sup.8R.sup.8', --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl, where the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two, three, four, five, six or seven groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; or one of R.sup.1 and R.sup.2 together with the carbon to which they are attached, R.sup.3 and R.sup.4 together with the carbon to which they are attached, and R.sup.5 and R.sup.6 together with the carbon to which they are attached form C(O) or C(.dbd.NOH); m is 1 or 2; R.sup.7 is hydrogen, halo or alkyl; and R.sup.8, R.sup.8' and R.sup.8'' are independently selected from hydrogen, hydroxy, optionally substituted alkoxy, alkyl, haloalkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, where the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two three, four, or five groups independently selected from alkyl, halo, hydroxy, hydroxyalkyl, optionally substituted alkoxy, alkoxyalkyl, haloalkyl, carboxy, carboxy ester, nitro, cyano, --S(O).sub.nR.sup.31 (where n is 0, 1, or 2 and R.sup.31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --NR.sup.36S(O).sub.2R.sup.36a (where R.sup.36 is hydrogen, alkyl, or alkenyl and R.sup.36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --S(O).sub.2NR.sup.37R.sup.37a (where R.sup.37 is hydrogen, alkyl, or alkenyl and R.sup.37a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted aryloxy, optionally substituted arylalkyloxy, optionally substituted heteroaryl, --NHC(O)R.sup.32 (where R.sup.32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and --NR.sup.30R.sup.30' (where R.sup.30 and R.sup.30' are independently hydrogen, alkyl, or hydroxyalkyl), and --C(O)NHR.sup.33 (where R.sup.33 is alkyl, alkenyl, alkynyl, or cycloalkyl); R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl; Group C: A is ##STR00474## where R.sup.10 is hydrogen, alkyl, alkenyl, alkynyl, halo, haloalkoxy, hydroxy, alkoxy, amino, alkylamino, dialkylamino, haloalkyl, --NHS(O).sub.2R.sup.8, --CN, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8' and --NR.sup.8C(O)R.sup.8'; R.sup.10a is hydrogen, alkyl, or alkenyl; Y.sup.1 is .dbd.CH-- or .dbd.N--; X is alkyl, halo, haloalkyl, or haloalkoxy; R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently hydrogen, halo, nitro, --NR.sup.8R.sup.8', --OR.sup.8, --NHS(O).sub.2R.sup.8, --CN, --S(O).sub.mR.sup.8, --S(O).sub.2NR.sup.8R.sup.8', --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl, where the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two, three, four, five, six or seven groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; or one of R.sup.1 and R.sup.2 together with the carbon to which they are attached, R.sup.3 and R.sup.4 together with the carbon to which they are attached, and R.sup.5 and R.sup.6 together with the carbon to which they are attached form C(O) or C(.dbd.NOH); m is 1 or 2; R.sup.7 is hydrogen, halo or alkyl; and R.sup.8, R.sup.8' and R.sub.8'' are independently selected from hydrogen, hydroxy, optionally substituted alkoxy, alkyl, haloalkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, where the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two three, four, or five groups independently selected from alkyl, halo, hydroxy, hydroxyalkyl, optionally substituted alkoxy, alkoxyalkyl, haloalkyl, carboxy, carboxy ester, nitro, cyano, --S(O).sub.nR.sup.31 (where n is 0, 1, or 2 and R.sup.31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --NR.sup.36S(O).sub.2R.sup.36a (where R.sup.36 is hydrogen, alkyl, or alkenyl and R.sup.36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --S(O).sub.2NR.sup.37R.sup.37a (where R.sup.37 is hydrogen, alkyl, or alkenyl and R.sup.37a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted aryloxy, optionally substituted arylalkyloxy, optionally substituted heteroaryl, --NHC(O)R.sup.32 (where R.sup.32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and --NR.sup.30R.sup.30' (where R.sup.30 and R.sup.30' are independently hydrogen, alkyl, or hydroxyalkyl), and --C(O)NHR.sup.33 (where R.sup.33 is alkyl, alkenyl, alkynyl, or cycloalkyl); R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl; or Group D: A is ##STR00475## R.sup.40 and R.sup.40a are independently hydrogen or alkyl; X is alkyl, halo, haloalkyl, or haloalkoxy; R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently hydrogen, halo, nitro, --NR.sup.8R.sup.8', --OR.sup.8, --NHS(O).sub.2R.sup.8, --CN, --S(O).sub.mR.sup.8, --S(O).sub.2NR.sup.8R.sup.8', --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl, where the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two, three, four, five, six or seven groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; or one of R.sup.1 and R.sup.2 together with the carbon to which they are attached, R.sup.3 and R.sup.4 together with the carbon to which they are attached, and R.sup.5 and R.sup.6 together with the carbon to which they are attached form C(O) or C(.dbd.NOH); m is 1 or 2; R.sup.7 is hydrogen, halo or alkyl; and R.sup.8, R.sup.8' and R.sup.8'' are independently selected from hydrogen, hydroxy, optionally substituted alkoxy, alkyl, haloalkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, where the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two three, four, or five groups independently selected from alkyl, halo, hydroxy, hydroxyalkyl, optionally substituted alkoxy, alkoxyalkyl, haloalkyl, carboxy, carboxy ester, nitro, cyano, --S(O).sub.nR.sup.31 (where n is 0, 1, or 2 and R.sup.31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --NR.sup.36S(O).sub.2R.sup.36a (where R.sup.36 is hydrogen, alkyl, or alkenyl and R.sup.36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --S(O).sub.2NR.sup.37R.sup.37a (where R.sup.37 is hydrogen, alkyl, or alkenyl and R.sup.37a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted aryloxy, optionally substituted arylalkyloxy, optionally substituted heteroaryl, --NHC(O)R.sup.32 (where R.sup.32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and --NR.sup.30R.sup.30' (where R.sup.30 and R.sup.30' are independently hydrogen, alkyl, or hydroxyalkyl), and --C(O)NHR.sup.33 (where R.sup.33 is alkyl, alkenyl, alkynyl, or cycloalkyl); R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl. 2. The Compound of claim 1 selected from Group B, and Group C where Group B A is thien-3,4-diyl, benzo[d]isoxazol-5,6-diyl, 1H-indazol-5,6-diyl (optionally substituted at the N1 position with R.sup.19 where R.sup.19 is alkyl or alkenyl), benzo[d]oxazol-5,6-diyl, 1H-benzo[d]imidazol-5,6-diyl (optionally substituted at the N1 position with R.sup.19 where R.sup.19 is alkyl or alkenyl), 1H-benzo[d][1,2,3]triazol-5,6-diyl (optionally substituted at the N1 position with R.sup.19 where R.sup.19 is alkyl or alkenyl), imidazo[1,2-a]pyridin-6,7-diyl, cinnolin-6,7-diyl, quinolin-6,7-diyl, pyridin-3,4-diyl, 1-oxido-pyridin-3,4-diyl, [1,2,4]triazolo[4,3-a]pyridin-6,7-diyl, or 2,3-dihydroimidazo[1,2-a]pyridin-6,7-diyl; where A is optionally substituted with one, two, or three groups independently selected from R.sup.10, R.sup.12, R.sup.14, R.sup.16 and R.sup.19 where R.sup.10, R.sup.12, R.sup.14 and R.sup.16 are independently hydrogen, alkyl, halo, or amino; and R.sup.19 is hydrogen or alkyl; X is halo; R.sup.1, R.sup.2, R.sup.5 and R.sup.6 are hydrogen; R.sup.3 is hydrogen or hydroxy; R.sup.4 is --NR.sup.8R.sup.8', heterocycloalkyl, heteroaryl, or alkyl; where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl; R.sup.7 is halo; R.sup.8 is hydrogen or alkyl; and R.sup.8' is hydrogen, alkyl, or cycloalkyl; where the cycloalkyl is optionally substituted with one or two groups independently selected from hydroxy and alkyl; Group C A is ##STR00476## R.sup.10 is hydrogen or halo; R.sup.10a is hydrogen or alkyl; Y.sup.1 is .dbd.CH-- or .dbd.N--; X is halo; R.sup.1, R.sup.2, R.sup.5 and R.sup.6 are hydrogen; R.sup.3 is hydrogen or hydroxy; R.sup.4 is --NR.sup.8R.sup.8', heterocycloalkyl, heteroaryl, or alkyl; where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl; R.sup.7 is halo; R.sup.8 is hydrogen or alkyl; and R.sup.8' is hydrogen, alkyl, or cycloalkyl; where the cycloalkyl is optionally substituted with one or two groups independently selected from hydroxy and alkyl. 3. The compound of claim 1 where R.sup.3 is halo, nitro, --NR.sup.8R.sup.8', --OR.sup.8, --NHS(O).sub.2R.sup.8, --CN, --S(O).sub.mR.sup.8, --S(O).sub.2NR.sup.8R.sup.8', --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl; where the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two, three, four, five, six or seven groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; and R.sup.4 is as defined in claim 1; or R.sup.3 and R.sup.4 together with the carbon to which they are attached form C(O) or C(.dbd.NOH); R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl. 4. The compound of claim 1 where R.sup.3 and R.sup.4 are independently halo, nitro, --NR.sup.8R.sup.8', --OR.sup.8, --NHS(O).sub.2R.sup.8, --CN, --S(O).sub.mR.sup.8, --S(O).sub.2NR.sup.8R.sup.8', --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl; where the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two, three, four, five, six or seven groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; or R.sup.3 and R.sup.4 together with the carbon to which they are attached form C(O) or C(.dbd.NOH); R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl. 5. The compound according to claim 1 wherein R.sup.7 is halo. 6. The compound according to claim 1 wherein X is halo. 7. The compound according to claim 1 wherein R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen. 8. The compound of claim 1 where R.sup.3 is hydrogen, halo, hydroxy, amino, or alkoxy. 9. The compound of claim 1 where R.sup.4 is hydrogen, --NR.sup.8R.sup.8', --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8 , --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), alkyl, alkenyl, cycloalkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with one, two, or three --OR.sup.8, halo, nitro, --S(O).sub.mR.sup.9, optionally substituted heterocycloalkyl, --NR.sup.8R.sup.8', --NR.sup.8C(O)R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --NR.sup.8C(O)OR.sup.8', aryl; where the cycloalkyl is optionally substituted with one or two --NR.sup.8R.sup.8'; where the heterocycloalkyl is optionally substituted with one or two groups independently selected from alkyl and --C(O)OR.sup.8; and where the heteroaryl is optionally substituted with --NR.sup.8R.sup.8'; R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl. 10. The Compound of claim 1 where R.sup.1 is halo, nitro, --NR.sup.8R.sup.8', --OR.sup.8, --NHS(O).sub.2R.sup.8, --CN, --S(O).sub.mR.sup.8, --S(O).sub.2NR.sup.8R.sup.8', --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), or --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl; where the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl are independently optionally substituted with one, two, three, four, five, six or seven groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl; R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl. 11. The Compound of claim 1 selected from Group B where A is thien-3,4-diyl, benzo[d]isoxazol-5,6-diyl, 1H-indazol-5,6-diyl (optionally substituted at the N1 position with R.sup.19 where R.sup.19 is alkyl or alkenyl), benzo[d]oxazol-5,6-diyl, 1H-benzo[d]imidazol-5,6-diyl (optionally substituted at the N1 position with R.sup.19 where R.sup.19 is alkyl or alkenyl), 1H-benzo[d][1,2,3]triazol-5,6-diyl (optionally substituted at the N1 position with R.sup.19 where R.sup.19 is alkyl or alkenyl), imidazo[1,2-a]pyridin-6,7-diyl, cinnolin-6,7-diyl, quinolin-6,7-diyl, pyridin-3,4-diyl, 1-oxido-pyridin-3,4-diyl, [1,2,4]triazolo[4,3-a]pyridin-6,7-diyl, or 2,3-dihydroimidazo[1,2-a]pyridin-6,7-diyl. 12. The Compound of claim 1 where A is thien-3,4-diyl; R.sup.10 and R.sup.12 are hydrogen; X and R.sup.7 are halo; and R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen. 13. The Compound of claim 12 where R.sup.3 is hydrogen or hydroxy; and R.sup.4 is --NR.sup.8R.sup.8', heterocycloalkyl, heteroaryl, or alkyl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8'. 14. The Compound of claim 1 selected from Group B where A is benzo[d]isoxazol-5,6-diyl; R.sup.10, R.sup.12, and R.sup.14 are independently hydrogen, halo, or alkyl; R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl. 15. The Compound of claim 11 according to Formula I(g) or I(h): ##STR00477## where R.sup.10, R.sup.12, and R.sup.14 are independently hydrogen, halo, or alkyl; R.sup.19 is alkyl or alkenyl; R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl. 16. The Compound of claim 11 according to Formula I(i) or I(j): ##STR00478## where R.sup.10, R.sup.12, and R.sup.14 are independently hydrogen, halo, or alkyl; R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl. 17. The Compound of 11 according to Formula I(n) or I(o): ##STR00479## where R.sup.7 is halo or alkyl; X is halo; R.sup.19 is alkyl; R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; R.sup.10, R.sup.12, and R.sup.14 are independently hydrogen or halo; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl. 18. The Compound of 11 according to Formula I(p): ##STR00480## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10 and R.sup.12 are independently hydrogen, halo, or alkyl; R.sup.19 is hydrogen or alkyl; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl. 19. The Compound of 11 according to Formula I(q): ##STR00481## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10, R.sup.12, R.sup.14, and R.sup.16 are independently hydrogen or halo; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl. 20. The Compound of 11 according to Formula I(r): ##STR00482## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10 and R.sup.12 are independently hydrogen, halo, or alkyl; R.sup.14 is hydrogen, halo, alkyl, or amino; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl. 21. The Compound of 11 according to Formula I(s): ##STR00483## R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10 and R.sup.12 are independently hydrogen, halo, or alkyl; R.sup.14 is hydrogen, halo, alkyl, or amino; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl. 22. The Compound of 11 according to Formula I(u), I(v), I(w), or I(x): ##STR00484## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10, R.sup.12, and R.sup.14 are independently hydrogen, halo, or alkyl; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl. 23. The Compound of claim 1 selected from Group C and according to Formula I(y) or I(z): ##STR00485## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10 is hydrogen, halo, or alkyl; R.sup.10a is alkyl; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl. 24. The Compound of claim 1 selected from Group D and according to Formula I(aa) or I(bb): ##STR00486## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl. 25. The compound according to claim 1 selected from the group consisting of: TABLE-US-00008 1-({4-[(2-fluoro-4-iodophenyl)amino]-3-thienyl}carbonyl)azetidin-3-amine; 3-[(dimethylamino)methyl]-1-({4-[(2-fluoro-4-iodophenyl)amino]-3- thienyl}carbonyl)azetidin-3-ol; 3-[(1S)-1-aminoethyl]-1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]imidazo- [1,2-a]pyridin- 6-yl}carbonyl)azetidin-3-ol; 1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-a]pyridin-6-yl}ca- rbonyl)-3-[(1S)- 1-(methylamino)ethyl]azetidin-3-ol; 3-(1H-benzimidazol-2-yl)-1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]imid- azo[1,2- a]pyridin-6-yl}carbonyl)azetidin-3-ol; 3-(1H-benzimidazol-2-yl)-1-({7-[(4-bromo-2-fluorophenyl)amino]-8-fluoroimi- dazo[1,2- a]pyridin-6-yl}carbonyl)azetidin-3-ol; 3-{[(1,1-dimethylethyl)amino]methyl}-1-({4-[(2-fluoro-4-iodophenyl)amino]-- 3- thienyl}carbonyl)azetidin-3-ol; 3-(1-aminoethyl)-1-({8-chloro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-- a]pyridin-6- yl}carbonyl)azetidin-3-ol; 1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-a]pyridin-6-yl}ca- rbonyl)-3-[(2S)- piperidin-2-yl]azetidin-3-ol; 1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-a]pyridin-6-yl}ca- rbonyl)-3-{(1S)- 1-[(2-hydroxy-2-methylcyclopentyl)amino]ethyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1H-im- idazol-2- yl)azetidin-3-ol; 1-({2-fluoro-3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}carbonyl)-3-[(2S- )-pyrrolidin-2- yl]azetidin-3-ol; 1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]-4-methylcinnolin-6-yl}carbon- yl)-3-[(2S)- piperidin-2-yl]azetidin-3-ol; 1-({4-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-1-methyl-1H-benzimidazol-6-y- l}carbonyl)-3- piperidin-2-ylazetidin-3-ol; 1-({5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-1-methyl-1H-benzimidazol-6-- yl}carbonyl)- 3-[(2S)-piperidin-2-yl]azetidin-3-ol; 1-({8-chloro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-a]pyridin-6-yl}ca- rbonyl)-3- piperidin-2-ylazetidin-3-ol; 1-({7-[(4-bromo-2-fluorophenyl)amino]-8-fluoroimidazo[1,2-a]pyridin-6-yl}c- arbonyl)-3- [(2S)-piperidin-2-yl]azetidin-3-ol; 1-({7-[(4-bromo-2-chlorophenyl)amino]-8-chloroimidazo[1,2-a]pyridin-6-yl}c- arbonyl)-3- piperidin-2-ylazetidin-3-ol; 1-({8-chloro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-a]pyridin-6-yl}ca- rbonyl)-3-[(2S)- piperidin-2-yl]azetidin-3-ol; 1-({7-[(4-bromo-2-chlorophenyl)amino]-8-chloroimidazo[1,2-a]pyridin-6-yl}c- arbonyl)-3- [(2S)-piperidin-2-yl]azetidin-3-ol; 1--({4-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-1-methyl-1H-benzimidazol-6-- yl}carbonyl)-3- [(2S)-piperidin-2-yl]azetidin-3-ol; 3-[(1S)-1-aminoethyl]-1-({5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-1-met- hyl-1H- benzimidazol-6-yl}carbonyl)azetidin-3-ol; 1-({5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-1-methyl-1H-benzimidazol-6-- yl}carbonyl)- 3-[(1S)-1-(methylamino)ethyl]azetidin-3-ol; 4-[(4-bromo-2-fluorophenyl)amino]-3-fluoro-5-({3-hydroxy-3-[(2S)-piperidin- -2-yl]azetidin-1- yl}carbonyl)pyridin-2(1H)-one; 4-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(2S)-piperidin-2-yl]azet- idin-1- yl}carbonyl)-1-methylpyridin-2(1H)-one; 4-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(2S)-piperidin-2-yl]azet- idin-1- yl}carbonyl)-1-methylpyridin-2(1H)-one; 4-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(1S)-1-(methylamino)prop- yl]azetidin-1- yl}carbonyl)-1-methylpyridin-2(1H)-one; 5-({3-[(1S)-1-(dimethylamino)ethyl]-3-hydroxyazetidin-1-yl}carbonyl)-4-[(2- -fluoro-4- iodophenyl)amino]-1-methylpyridin-2(1H)-one; 4-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(methylamino)methyl]azet- idin-1- yl}carbonyl)-1-methylpyridin-2(1H)-one; 5-{[3-(1H-benzimidazol-2-yl)-3-hydroxyazetidin-1-yl]carbonyl}-4-[(4-bromo-- 2- fluorophenyl)amino]-1-methylpyridin-2(1H)-one; 4-[(4-bromo-2-fluorophenyl)amino]-5-{[3-hydroxy-3-(1-methyl-1H-benzimidazo- l-2- yl)azetidin-1-yl]carbonyl}-1-methylpyridin-2(1H)-one; 4-[(4-bromo-2-fluorophenyl)amino]-5-({3-hydroxy-3-[(2S)-pyrrolidin-2-yl]az- etidin-1- yl}carbonyl)-1-methylpyridin-2(1H)-one; 1-({6-[(4-bromo-2-chlorophenyl)amino]-7-fluoro-3-methyl-1,2-benzisoxazol-5- -yl}carbonyl)- 3-[(2S)-piperidin-2-yl]azetidin-3-ol; 5-[(2-fluoro-4-iodophenyl)amino]-6-({3-hydroxy-3-[(2S)-piperidin-2-yl]azet- idin-1- yl}carbonyl)-2-methylpyridazin-3(2H)-one; 5-[(4-bromo-2-chlorophenyl)amino]-6-({3-hydroxy-3-[(2S)-piperidin-2-yl]aze- tidin-1- yl}carbonyl)-2-methylpyridazin-3(2H)-one; 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-6-({3-hydroxy-3-[(2S)-pyrrolidi- n-2-yl]azetidin- 1-yl}carbonyl)-2-methylpyridazin-3(2H)-one; 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-6-({3-hydroxy-3-[(2R)-pyrrolidi- n-2-yl]azetidin- 1-yl}carbonyl)-2-methylpyridazin-3(2H)-one; 6-({3-[(1S)-1-aminoethyl]-3-hydroxyazetidin-1-yl}carbonyl)-5-[(2-fluoro-4-- iodophenyl)amino]-2-methylpyridazin-3(2H)-one; 6-({3-[(1S)-1-aminoethyl]-3-hydroxyazetidin-1-yl}carbonyl)-5-[(4-bromo-2- chlorophenyl)amino]-2-methylpyridazin-3(2H)-one; 5-[(4-bromo-2-chlorophenyl)amino]-6-{[3-((1S)-1-{[(3R,4S)-3,4- dihydroxycyclopentyl]amino}ethyl)-3-hydroxyazetidin-1-yl]carbonyl}-2- methylpyridazin-3(2H)-one; 5-[(4-bromo-2-fluorophenyl)amino]-6-[(3-hydroxy-3-{(1S)-1-[(2-hydroxy-2- methylcyclopentyl)amino]propyl}azetidin-1-yl)carbonyl]-2-methylpyridazin-3- (2H)- one; 6-({3-[(1S)-1-aminopropyl]-3-hydroxyazetidin-1-yl}carbonyl)-5-[(4-bromo-2-- fluorophenyl)amino]-2-methylpyridazin-3(2H)-one; 6-{[3-(1H-benzimidazol-2-yl)-3-hydroxyazetidin-1-yl]carbonyl}-5-[(2-fluoro- -4- iodophenyl)amino]-2-methylpyridazin-3(2H)-one; 5-[(2-fluoro-4-iodophenyl)amino]-6-{[3-hydroxy-3-(1-methyl-1H-benzimidazol- -2-yl)azetidin- 1-yl]carbonyl}-2-methylpyridazin-3(2H)-one; 1-({2-fluoro-3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}carbonyl)-3-[(2S- )-piperidin-2- yl]azetidin-3-ol; 1-({3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}carbonyl)-3-[(2S)-piperid- in-2-yl]azetidin- 3-ol; 1-({3-[(2-fluoro-4-iodophenyl)amino]-1-oxidopyridin-4-yl}carbonyl)-3-[(2S)- -piperidin-2- yl]azetidin-3-ol; 1-({2-fluoro-3-[(2-fluoro-4-bromophenyl)amino]pyridin-4-yl}carbonyl)-3-[(2- S)-piperidin-2- yl]azetidin-3-ol; 3-[(1S)-1-aminopropyl]-1-({3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}ca- rbonyl)azetidin- 3-ol; 1-({3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}carbonyl)-3-[(1S)-1- (methylamino)propyl]azetidin-3-ol; (1R,2S)-4-({(1S)-1-[1-({2-fluoro-3-[(2-fluoro-4-iodophenyl)amino]pyridin-4- -yl}carbonyl)-3- hydroxyazetidin-3-yl]propyl}amino)cyclopentane-1,2-diol; 1-({7-[(4-bromo-2-chlorophenyl)amino]-8-fluoro-4-methylcinnolin-6-yl}carbo- nyl)-3-[(2S)- piperidin-2-yl]azetidin-3-ol; 1-({7-[(4-bromo-2-fluorophenyl)amino]-8-fluoro-4-methylcinnolin-6-yl}carbo- nyl)-3-[(2S)- piperidin-2-yl]azetidin-3-ol; 3-[(1S)-1-aminoethyl]-1-({7-[(4-bromo-2-fluorophenyl)amino]cinnolin-6- yl}carbonyl)azetidin-3-ol; 1-({7-[(4-bromo-2-fluorophenyl)amino]cinnolin-6-yl}carbonyl)-3-{(1S)-1-[(2- -hydroxy-2- methylcyclopentyl)amino]ethyl}azetidin-3-ol; 1-({7-[(4-bromo-2-fluorophenyl)amino]cinnolin-6-yl}carbonyl)-3-[(1S)-1- (dimethylamino)ethyl]azetidin-3-ol; 3-[(1S)-1-aminoethyl]-1-({5-[(2-fluoro-4-iodophenyl)amino]-1H-1,2,3-benzot- riazol-6- yl}carbonyl)azetidin-3-ol; 3-[(1S)-1-(dimethylamino)ethyl]-1-({5-[(2-fluoro-4-iodophenyl)amino]-1-met- hyl-1H-1,2,3- benzotriazol-6-yl}carbonyl)azetidin-3-ol; 1-({5-[(2-fluoro-4-iodophenyl)amino]-1H-1,2,3-benzotriazol-6-yl}carbonyl)-- 3-[(2S)- piperidin-2-yl]azetidin-3-ol; 1-({5-[(2-fluoro-4-iodophenyl)amino]-1-methyl-1H-1,2,3-benzotriazol-6-yl}c- arbonyl)-3- [(2S)-piperidin-2-yl]azetidin-3-ol; 1-({5-[(2-fluoro-4-iodophenyl)amino]-1H-1,2,3-benzotriazol-6-yl}carbonyl)-- 3-{(1S)-1-[(2- hydroxy-2-methylcyclopentyl)amino]ethyl}azetidin-3-ol; 3-[(1S)-1-aminoethyl]-1-({4-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-1H-1,2- ,3-benzotriazol- 6-yl}carbonyl)azetidin-3-ol; 1-({4-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-1H-1,2,3-benzotriazol-6-yl}c- arbonyl)-3-[(2S)- piperidin-2-yl]azetidin-3-ol; 5-({3-[(1S)-1-aminoethyl]-3-hydroxyazetidin-1-yl}carbonyl)-6-[(2-fluoro-4-- iodophenyl)amino]pyrimidin-2(1H)-one; 6-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(2S)-piperidin-2-yl]azet- idin-1- yl}carbonyl)pyrimidin-2(1H)-one; 4-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(2S)-piperidin-2-yl]azet- idin-1- yl}carbonyl)pyrimidin-2(1H)-one; and 5-({3-[(1S)-1-aminoethyl]-3-hydroxyazetidin-1-yl}carbonyl)-4-[(2-fluoro-4-- iodophenyl)amino]pyrimidin-2(1H)-one; and pharmaceutically acceptable salts thereof. 26. A pharmaceutical composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent.