Claims for Patent: 6,407,103

Summary for Patent: 6,407,103

Title:	Indeno [1,2-c] pyrazol-4-ones and their uses
Abstract:	The present invention relates to the synthesis of a new class of indeno[1,2-c]pyrazol-4-ones of formula (I): ##STR1## that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cdk1-9 and their regulatory subunits know as cyclins A-H. This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.
Inventor(s):	Nugiel; David A. (Cherry Hill, NJ), Carini; David J. (Wilmington, DE), Di Meo; Susan V. (Wilmington, DE), Yue; Eddy W. (Landenberg, PA)
Assignee:	Bristol-Myers Squibb Pharma Company (Wilmington, DE)
Application Number:	09/731,304
Patent Claims:	1. A compound according to formula (I): ##STR42## or stereoisomers, pharmaceutically acceptable salts, and prodrugs thereof, wherein: X is selected from the groups: O, S, and NR; R is selected from the groups: H, C.sub.1-4 alkyl, and NR.sup.5 R.sup.5a ; R.sup.1 is selected from the groups: H, C.sub.1-10 alkyl substituted with 0-3 R.sup.c, C.sub.2-10 alkenyl substituted with 0-3 R.sup.c, C.sub.2-10 alkynyl substituted with 0-3 R.sup.c, --NHR.sup.4, C.sub.3-10 membered carbocycle substituted with 0-5 R.sup.a, and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b ; R.sup.a is independently selected from the groups: R.sup.5 R.sup.5a N(CR.sup.6 R.sup.6a)m, R.sup.5 O(CR.sup.6 R.sup.6a)m, halo, --CN, N.sub.3, NO.sub.2, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, NR.sup.3 R.sup.3a, .dbd.O, OR.sup.3, SR.sup.3, COR.sup.3, CO.sub.2 R.sup.3, CONR.sup.3 R.sup.3a, NHC(O)NR.sup.3 R.sup.3a, NHC(S)NR.sup.3 R.sup.3a, NR.sup.3 C(O)OR.sup.3, NR.sup.3 C(O)R.sup.3, SO.sub.2 NR.sup.3 R.sup.3a, SO.sub.2 R.sup.3b, and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S; alternatively, when two R.sup.a 's are present on adjacent carbon atoms they combine to form --OCH.sub.2 O-- or --OCH.sub.2 CH.sub.2 O--; R.sup.b is independently selected from the groups: halo, --CN, NO.sub.2, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, NR.sup.3 R.sup.3a, NR.sup.3 C(O)OR.sup.3, NR.sup.3 C(O)R.sup.3, OR.sup.3, COR.sup.3, CO.sub.2 R.sup.3, CONR.sup.3 R.sup.3a, CON(R.sup.6)((CH.sub.2).sub.m R.sup.7), CO(CH.sub.2).sub.m R.sup.7, NHC(O)NR.sup.3 R.sup.3a, NHC(S)NR.sup.3 R.sup.3a, SO.sub.2 NR.sup.3 R.sup.3a, and SO.sub.2 R.sup.3b ; R.sup.c is independently selected from the groups: halo, --CN, NO.sub.2, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, NR.sup.3 R.sup.3a, NR.sup.5 NR.sup.5 R.sup.5a, NR.sup.3 C(O)OR.sup.3, NR.sup.3 C(O)R.sup.3, .dbd.O, OR.sup.3, COR.sup.3, CO.sub.2 R.sup.3, CONR.sup.3 R.sup.3a, NHC(O)NR.sup.3 R.sup.3a, NHC(S)NR.sup.3 R.sup.3a, SO.sub.2 N.sup.3 R.sup.3a, SO.sub.2 R.sup.3b, C.sub.3-10 membered carbocycle substituted with 0-5 R.sup.a, and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R.sup.3 ; R.sup.2 is selected from the groups: H, C.sup.1-10 alkyl substituted with 0-3 R.sup.c, C.sub.2-10 alkenyl substituted with 0-3 R.sup.c, C.sub.2-10 alkynyl substituted with 0-3 R.sup.c, --(CF.sub.2).sub.m CF.sup.3, C.sub.3-10 membered carbocycle substituted with 0-5 R.sup.a, and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b ; R.sup.3 is independently selected from the groups: H, halo, --CN, NO.sub.2, C.sub.1-4 haloalkyl, R.sup.5 R.sup.5a N(CR.sup.6 R.sup.6a)m, NR.sup.5 NR.sup.5 R.sup.5a, NR.sup.5 C(O)OR.sup.5, NR.sup.5 C(O)R.sup.5, .dbd.O, R.sup.5 O(CR.sup.6 R.sup.6a)m, COR.sup.5, CO.sub.2 R.sup.5, CONR.sup.5 R.sup.5a, NHC(O)NR.sup.5 R.sup.5a, NHC(S)NR.sup.5 R.sup.5a, SO.sub.2 NR.sup.5 R.sup.5a, SO.sub.2 R.sup.5b, C.sub.1-4 alkyl, phenyl, and benzyl; R.sup.3a is independently selected from the groups: H, C.sub.1-4 alkyl, phenyl, and benzyl; alternatively, R.sup.3 and R.sup.3a, together with the atoms to which they are attached, form a heterocycle having 4-8 atoms in the ring and containing an additional 0-1 N, S, or O atom and substituted with 0-3 R.sup.3c ; R.sup.3b is independently selected from the groups: H, C.sub.1-4 alkyl, phenyl, and benzyl; R.sup.3c is independently selected from the groups: halo, --CN N.sub.3, NO.sub.2, C.sub.1-4 alkyl, C.sub.3-8 cycloalkyl, C.sub.4-10 cycloalkylalkyl, C.sub.1-4 haloalkyl, NR.sup.3 R.sup.3b, R.sup.5 R.sup.5a N(CR.sup.6 R.sup.6a)m, .dbd.O, OR.sup.3, R.sup.5 O(CR.sup.6 R.sup.6a)m, COR.sup.3, CO.sub.2 R.sup.3, CONR.sup.3 R.sup.3.sup..sup.b , NHC(O)NR.sup.3 R.sup.3.sup..sup.b , NHC(S)NR.sup.3 R.sup.3.sup..sup.b , NR.sup.3 C(O)OR.sup.3, NR.sup.3 C(O)R.sup.3, C(.dbd.NR.sup.5)R.sup.5a, C(.dbd.NR.sup.5)NR.sup.5a R.sup.5b, SO.sub.2 NR.sup.3 R.sup.3.sup..sup.b , SO.sub.2 R.sup.3b, and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S; R.sup.4 is independently selected from the groups: H, --CN, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, NR.sup.3 R.sup.3a, NR.sup.3 C(O)OR.sup.3, NR.sup.3 C(O)R.sup.3, OR.sup.3, COR.sup.3, CO.sub.2 R.sup.3, CONR.sup.3 R.sup.3a, NHC(O)NR.sup.3 R.sup.3a, NHC(S)NR.sup.3 R.sup.3a, SO.sub.2 NR.sup.3 R.sup.3a, SO.sub.2 R.sup.3b, C.sub.3-10 membered carbocycle substituted with 0-5 R.sup.a, and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R.sup.3 ; R.sup.5 is independently selected from the groups: H, C.sub.1-4 alkyl, phenyl and benzyl; R.sup.5a is independently selected from the groups: H, C.sub.1-4 alkyl, phenyl and benzyl; alternatively, R.sup.5 and R.sup.5a, together with the atoms to which they are attached, form a heterocycle having 4-8 atoms in the ring and containing an additional 0-1 N, S, or O atom; R.sup.5b is independently selected from the groups: H, C.sub.1-4 alkyl, phenyl and benzyl; R.sup.6 is idependently selected from the groups: H, C.sub.1-4 alkyl; R.sup.6a is independently selected from the groups: H, C.sub.1-4 alkyl; R.sup.7 is independently selected from the groups: NR.sup.3 R.sup.3a, C.sub.3-10 membered carbocycle substituted with 0-3 R.sup.3, and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R.sup.3 ; and m is independently selected from 0, 1, 2, 3, and 4; provided that: when R.sup.2 is a C.sub.1-4 unsubstituted, branched alkyl then R.sup.1 is not CH.sub.3 ; or when R.sup.1 is NHR.sup.4 and R.sup.4 is NR.sup.3 R.sup.3a then R.sup.3 and R.sup.3a can not both be phenyl. 2. A compound according to claim 1, wherein X is O or S; R.sup.1 is H, C.sub.1-10 alkyl substituted with 0-3 R.sup.c, --NHR.sup.4, C.sub.3-10 membered carbocycle substituted with 0-5 R.sup.a, or 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5; R.sup.c is independently selected from the groups: halo, C.sub.3-10 membered carbocycle substituted with 0-5 R.sup.a, 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R.sup.3, NR.sup.3 R.sup.3a ; R.sup.3 is H, C.sub.1-4 alkyl, phenyl, benzyl, or together with the atoms to which they are attached, form a heterocycle having 4-8 atoms in the ring and containing an additional 0-1 N, S, or O atom and substituted with 0-3 R.sup.3c ; R4 is H, C.sub.1-4 alkyl, NR.sup.3 R.sup.3a, C.sub.3-10 membered carbocycle substituted with 0-5 R.sup.a, and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R.sup.3 ; R.sup.2 is selected from the groups: C.sub.3-10 membered carbocycle substituted with 0-5 R.sup.a, and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b, and C.sub.1-10 alkyl substituted with 0-3 R.sup.c. 3. A compound according to claim 1, wherein X is O or S; R.sup.1 is C.sub.1-4 alkyl substituted with 0-3 R.sup.c, wherein R.sup.c is independently selected from the group consisting of: C.sub.3-6 membered carbocycle substituted with 0-5 R.sup.a, 5-6 membered heterocycle substituted with 0-3 R.sup.3, NR.sup.3 R.sup.3a, and OR.sup.3 ; C.sub.3-6 membered carbocycle substituted with 0-5 R.sup.a, wherein R.sup.a is independently selected from the group consisting of: R.sup.5 R.sup.5a N(CR.sup.6 R.sup.6a)m--, R.sup.5 O(CR.sup.6 R.sup.6a)m--, OR.sup.3, halo, C.sub.1-4 alkyl, --NR.sup.3 C(O)R.sup.3, COR.sup.3, CO.sub.2 R.sup.3, N.sub.3, NR.sup.3 C(O)OR.sup.3, NR.sup.3 R.sup.3a, CONR.sup.3 R.sup.3a, and 5-6 membered heterocycle; or when two R.sup.a 's are present on adjacent carbon atoms they combine to form --OCH.sub.2 O-- or --OCH.sub.2 CH.sub.2 O--; or 5-6 membered heterocycle and substituted with 0-5 R.sup.b, wherein R.sup.b is independently selected from the group: OR.sup.3, halo, COR.sup.3, C.sub.1-4 alkyl, CO.sub.2 R.sup.3, NR.sup.3 C(O)R.sup.3, NR.sup.3 C(O)OR.sup.3, NR.sup.3 R.sup.3a, and CONR.sup.3 R.sup.3a ; R.sup.2 is C.sub.3-6 membered carbocycle substituted with 0-5 R.sup.a, wherein R.sup.a is independently selected from the groups: R.sup.5 R.sup.5a N(CR.sup.6 R.sup.6a)m, R.sup.5 O(CR.sup.6 R.sup.6a)m, OR.sup.3, halo, C.sub.1-4 alkyl, NR.sup.3 C(O)R.sup.3, COR.sup.3, CO.sub.2 R.sup.3, N.sub.3, NR.sup.3 C(O)OR.sup.3, NR.sup.3 R.sup.3a, CONR.sup.3 R.sup.3a, and 5-6 membered heterocycle, or when two R.sup.a 's are present on adjacent carbon atoms they combine to form --OCH.sub.2 O-- or --OCH.sub.2 CH.sub.2 O--; 3-6 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b, wherein R.sup.b is independently selected from the group: OR.sup.3, halo, COR.sup.3, C.sub.1-4 alkyl, CO.sub.2 R.sup.3, NR.sup.3 C(O)R.sup.3, NR.sup.3 C(O)OR.sup.3, NR.sup.3 R.sup.3a, and CONR.sup.3 R.sup.3a ; or C.sub.1-10 alkyl substituted with 0-3 R.sup.c, wherein R.sup.c is independently selected from the groups: C.sub.3-6 membered carbocycle substituted with 0-5 R.sup.a, 5-6 membered heterocycle substituted with 0-3 R.sup.3, NR.sup.3 R.sup.3a, and OR.sup.3. 4. A compound according to claim 1, wherein X is O or S; R.sup.1 is selected from the groups: H, --NHR.sup.4, C.sub.1-4 alkyl substituted with 0-3 R.sup.c, C.sub.3-6 membered carbocycle substituted with 0-5 R.sup.a, and 5-6 membered heterocycle and substituted with 0-5 R.sup.b ; R.sup.2 is selected from the group: C.sub.3-6 membered carbocycle substituted with 0-5 R.sup.a, 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b, and C.sub.1-10 alkyl substituted with 0-3 R.sup.c, C.sub.2-10 alkenyl substituted with 0-3 R.sup.c ; R.sup.4 is independently selected from the groups: H, C.sub.1-4 alkyl, NR.sup.3 R.sup.3a, 3-6 membered carbocycle substituted with 0-5 R.sup.a, and 5-6 membered heterocycle substituted with 0-3 R.sup.3 ; R.sup.3 is independently selected from the group: H, halo, COR.sup.5, CO.sub.2 R.sup.5, R.sup.5 R.sup.5a N(CR.sup.6 R.sup.6a)m, R.sup.5 O(CR.sup.6 R.sup.6a)m, CONR.sup.5 R.sup.5a, NR.sup.5 C(O)OR.sup.5, NR.sup.5 C(O)R.sup.5, C.sub.1-4 alkyl, phenyl, and benzyl; R.sup.3a is independently selected from the group: H, C.sub.1-4 alkyl, phenyl, and benzyl; or R.sup.3 and R.sup.3a, together with the atoms to which they are attached, form a 5-6 membered heterocycle containing an additional 0-1 N, S, or O atom and substituted with 0-3 R.sup.3c ; R.sup.c is independently selected from the groups: C.sub.3-6 membered carbocycle substituted with 0-5 R.sup.a, 5-6 membered heterocycle substituted with 0-3 R.sup.3, NR.sup.3 R.sup.3a, and OR.sup.3 ; R.sup.a is independently selected from the groups: R.sup.5 R.sup.5a N(CR.sup.6 R.sup.6a)m, R.sup.5 O(CR.sup.6 R.sup.6a)m, OR.sup.3, halo, C.sub.1-4 alkyl, NR.sup.3 C(O)R.sup.3, COR.sup.3, CO.sub.2 R.sup.3, N.sub.3, NR.sup.3 C(O)OR.sup.3, NR.sup.3 R.sup.3a, CONR.sup.3 R.sup.3a, 5-6 membered heterocycle; or when two R.sup.a 's are present on adjacent carbon atoms they combine to form --OCH.sub.2 O-- or --OCH.sub.2 CH.sub.2 O--; R.sup.b is independently selected from the group: OR.sup.3, halo, COR.sup.3, C.sub.1-4 alkyl, CO.sub.2 R.sup.3, NR.sup.3 C(O)R.sup.3, NR.sup.3 C(O)OR.sup.3, NR.sup.3 R.sup.3a, CONR.sup.3 R.sup.3a ; R.sup.3c is independently selected from the groups: OR.sup.3, halo, COR.sup.3, R.sup.5 R.sup.5a N(CR.sup.6 R.sup.6a)m--, R.sup.5 O)(CR.sup.6 R.sup.6a)m--, CO.sub.2 R.sup.3, N.sub.3, NR.sup.3 R.sup.3b, C.sub.1-4 alkyl, NR.sup.3 C(O)R.sup.3, NR.sup.3 C(O)OR.sup.3, N.sub.3, NR.sup.3 R.sup.3b, CONR.sup.3 R.sup.3b, and 5-6 membered heterocycle; and m is independently selected from the group consisting of 1 2, 3 and 4. 5. A compound according to claim 1, wherein R.sup.1 is selected from the group: --NHR.sup.4 and C.sub.1-2 alkyl substituted with 1 R.sup.c. 6. A compound according to claim 1 wherein X is O or S; and R.sup.1 is selected from the group: H, C.sub.1-4 alkyl substituted with 0-3 R.sup.c, C.sub.2-4 alkenyl substituted with 0-3 R.sup.c, C.sub.2-4 alkynyl substituted with 0-3 R.sup.C, --NHR.sup.4, C.sub.3-6 carbocycle substituted with 0-5 R.sup.a, and 3-6 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b. 7. A compound according to claim 1 wherein X is O or S; and R.sup.1 is selected from the group: H, C.sub.1-4 alkyl substituted with 0-3 R.sup.c, C.sub.2-4 alkenyl substituted with 0-3 R.sup.c, C.sub.2-4 alkynyl substituted with 0-3 R.sup.c, --NHR.sup.4, C.sub.3-6 carbocycle substituted with 0-5 R.sup.a, and 3-6 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b ; R.sup.a is independently at each occurrence selected from the group: --CH.sub.2 N(CH.sub.3).sub.2, --CH.sub.2 NH.sub.2, --SH, --SCH.sub.3, --NR.sub.3 C(O)R.sub.3, --N.sub.3, halo, C.sub.1-4 alkyl, NR.sup.3 R.sup.3a, and OR.sup.3 ; alternatively, when two R.sup.a 's are present on adjacent carbon atoms they combine to form --OCH.sub.2 O-- or --OCH.sub.2 CH.sub.2 O--; R.sup.b is independently at each occurrence selected from the group: halo, C.sub.1-4 alkyl, NR.sup.3 R.sup.3a, OR.sup.3, COR.sup.3, and CO.sub.2 R.sup.3 ; R.sup.c is independently at each occurrence selected from the group: halo, C.sub.1-4 alkyl, NR.sup.3 R.sup.3a, C.sub.3-6 carbocycle substituted with 0-5 R.sup.a, and 5-7 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R.sup.3 ; R.sup.3a is H or C.sub.1-4 alkyl; and R.sup.3 is selected from the group: H, --CH.sub.2 CH.sub.2 OH, --C(O)CH.sub.2 NH.sub.2, --C(O)CH.sub.2 N(CH3)2, --NR.sup.5 R.sup.5a, --C.sub.1-4 alkyl-NR.sup.5 R.sup.5a, C.sub.1-4 alkyl, phenyl, and benzyl. 8. A compound according to claim 1 wherein X is O or S; R.sup.1 is selected from the group: H, C.sub.1-4 alkyl substituted with 0-3 R.sup.c, --NHR.sup.4, C.sub.3-6 carbocycle substituted with 0-5 R.sup.a, and 3-6 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b ; R.sup.a is independently at each occurrence selected from the group: --CH.sub.2 N(CH.sub.3).sub.2, --CH.sub.2 NH.sub.2, --SH, --SCH.sub.3, halo, C.sub.1-4 alkyl, NR.sup.3 R.sup.3a, and OR.sup.3 ; alternatively, when two R.sup.a 's are present on adjacent carbon atoms they combine to form --OCH.sub.2 O-- or --OCH.sub.2 CH.sub.2 O --; R.sup.b is independently at each occurrence selected from the group: halo, C.sub.1-4 alkyl, NR.sup.3 R.sup.3a, OR.sup.3, COR.sup.3, and CO.sub.2 R.sup.3 ; R.sup.c is independently at each occurrence selected from the group: --OH, chloro, C.sub.1-4 alkyl, --NH2, --NHCH3, --NHCH2CH3, --NHCH2CH2CH3, --NHCH2CH2OH, --N(CH3)2, phenyl substituted with 0-5 R.sup.a, and 5-7 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R.sup.3. 9. A compound according to claim 1 wherein R.sup.1 is selected from the group: H, C.sub.1-10 alkyl substituted with 0-3 R.sup.c, C.sub.2-10 alkenyl substituted with 0-3 R.sup.c, C.sub.2-10 alkynyl substituted with 0-3 R.sup.c ; R.sup.2 is selected from the group: H, --(CF.sub.2).sub.m CF.sub.3, C.sub.3-10 carbocycle substituted with 0-5 R.sup.a, and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b ; and R.sup.c is independently at each occurrence selected from the group: phenyl substituted with 0-5 R.sup.a, and thiophenyl or pyridyl, which is substituted with 0-3 R.sup.3. 10. A compound according to claim 1 wherein R.sup.1 is selected from the group: H, C.sub.1-10 alkyl substituted with 0-3 R.sup.c, C.sub.2-10 alkenyl substituted with 0-3 R.sup.c, C.sub.2-10 alkynyl substituted with 0-3 R.sup.c ; R.sup.2 is selected from the group: H, --(CF.sub.2).sub.m CF.sub.3, C.sub.3-10 carbocycle substituted with 0-5 R.sup.a, and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b ; and R.sup.c is independently at each occurrence selected from the group: thiophenyl, piperazinyl, piperidinyl, thiomorpholinyl, morpholinyl, pyrrolidinyl, and pyridyl, which is substituted with 0-3 substituents indepently selected from the group consiting of CH3, CH2CH2OH, CH2CH2NH2, --C(.dbd.O)NH2, --OCH3, CH2NH2, NHCH2CH3,OH, NH2, halo, --CH2N(CH3)2, --OCH2CH2O--,--OCH2O--, --N(CH3)2, uridomethyl, and pyridyl. 11. A compound according to claim 1 wherein R.sup.1 is selected from the group: H, C.sub.1-10 alkyl substituted with 0-3 R.sup.c, C.sub.2-10 alkenyl substituted with 0-3 R.sup.c, C.sub.2-10 alkynyl substituted with 0-3 R.sup.c ; R.sup.2 is selected from the group: H, --(CF.sub.2).sub.m CF.sub.3, C.sub.3-10 carbocycle substituted with 0-5 R.sup.a, and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b ; and R.sup.c is phenyl substituted with 0-5 substituents indepently selected from the group consiting of CH3, CH2CH2OH, CH2CH2NH2, --C(.dbd.O)NH2, --OCH3, CH2NH2, NHCH2CH3, OH, NH2, halo, --CH2N(CH3)2, --OCH2CH2O--, --OCH2O--, --N(CH3)2, uridomethyl, and pyridyl. 12. A compound according to claim 1 wherein X is O or S; R.sup.1 is --NHR.sup.4 or methylene substituted with 0-3 R.sup.c ; R.sup.c is NR.sup.3 R.sup.3a ; R.sup.4 is selected from the group consisting of H, C1-4 alkyl, and NR.sup.3 R.sup.3a ; and R.sup.3 and R.sup.3a, are independently hydrogen or C1-4alkyl, or R.sup.3 and R.sup.3a, together with the nitrogen atom to which they are attached, form a 4-8 membered heterocycle containing an additional 0-1 N, S, or O atom and substituted with 0-3 R.sup.3c. 13. A compound according to claim 1 wherein X is O or S; R.sup.1 is --NHR.sup.4 or methylene substituted with 0-3 R.sup.c ; R.sup.c is NR.sup.3 R.sup.3a ; R.sup.4 is selected from the group consisting of H, C1-4 alkyl, and NR.sup.3 R.sup.3a ; and R.sup.3 and R.sup.3a, are independently hydrogen or C1-4alkyl, or R.sup.3 and R.sup.3a, together with the nitrogen atom to which they are attached, form a 4-8 membered heterocycle containing an additional 0-1 N, S, or O atom and substituted with with 0-3 substituents independently selected from the group consisting of methyl, --CH.sub.2 OCH.sub.3, --C(CH.sub.3).sub.2 OCH.sub.3, --CH.sub.2 CH.sub.2 OH, --CH.sub.2 OH, --CH.sub.2 OCH.sub.2 Phenyl, --CH.sub.2 CH.sub.2 NH.sub.2, --CH.sub.2 NH.sub.2, --C(.dbd.NH)CH.sub.3, and NH2. 14. A compound according to claim 1 wherein X is O or S; and R.sup.1 is selected from the group: methylene substituted with a substituent selected from the group consisting of: halo, NR.sup.3 R.sub.3a, C.sub.3-6 carbocycle substituted with 0-5 R.sup.a, and 5-7 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R.sup.3. 15. A compound according to claim 1 wherein X is O or S; R.sup.1 is selected from the group: methylene substituted with NR.sup.3 R.sup.3a ; and R.sup.3 and R.sup.3a, together with the nitrogen atom to which they are attached, form pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, thiomorpholinyl, pymorpholinyl, piperidinyl, piperazinyl, or piperadinyl, which is substituted with 0-3 R.sup.3c. 16. A compound according to claim 1 wherein R.sup.1 is --NHR.sup.4 ; R.sup.4 is NR3R3a; and R.sup.3 and R.sup.3a, together with the nitrogen atom to which they are attached, form pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, thiomorpholinyl, pymorpholinyl, piperidinyl, piperazinyl, or piperadinyl, which is substituted with 0-3 R.sup.3c. 17. A compound according to claim 1 wherein R.sup.1 is --NHR.sup.4 ; R.sup.4 is NR3R3a; and R.sup.3 and R.sup.3 a, together with the nitrogen atom to which they are attached, form pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, thiomorpholinyl, pymorpholinyl, piperidinyl, piperazinyl, or piperadinyl, which is substituted with 0-3 substituents independently selected from the group consisting of methyl, --CH.sub.2 OCH.sub.3, --C(CH.sub.3).sub.2 OCH.sub.3, --CH.sub.2 CH.sub.2 OH, --CH.sub.2 OH, --CH.sub.2 OCH.sub.2 Phenyl, --CH.sub.2 CH.sub.2 NH.sub.2, --CH.sub.2 NH.sub.2, --C(.dbd.NH)CH.sub.3, and NH2. 18. A compound according to claim 1, wherein R.sup.2 is selected from the group: 5- to 7- membered monocyclic saturated, or partially saturated, heterocyclic ring substituted with 0-5 R.sup.b. 19. A compound according to claim 1, wherein R.sup.2 is selected from the group: 5- to 7- membered monocyclic aromatice heterocyclic ring substituted with 0-5 R.sup.b. 20. A compound according to claim 1, wherein R.sup.2 is selected from the group: C.sub.1-10 alkyl substituted with 0-3 R.sup.c, C.sub.3-10 carbocycle substituted with 0-5 R.sup.a, and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b. 21. A compound according to claim 1, wherein R.sup.2 is selected from the group: C.sub.1-6 alkyl substituted with 0-3 R.sup.c, C.sub.3-6 carbocycle substituted with 0-5 R.sup.a, and 3-7 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R.sup.b. 22. A compound according to claim 1, wherein R.sup.2 is selected from the group: C.sub.1-6 alkyl substituted with C.sub.3-10 carbocycle substituted with 0-5 R.sup.a, and C.sub.1-6 alkyl substituted with 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S. 23. A compound according to claim 1, wherein R.sup.2 is selected from the group: phenyl substituted with 0-5 R.sup.a, and cyclopropyl or cyclohexyl substituted with 0-2 R.sup.a ; and R.sup.a is independently at each occurrence selected from the group: --CH.sub.2 N(CH.sub.3).sub.2, --CH.sub.2 NH.sub.2, --SR.sup.3 halo, --CN , N.sub.3, NO.sub.2, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, NR.sup.3 R.sup.3a, .dbd.O, OR.sup.3, COR.sup.3, CO.sub.2 R.sup.3, CONR.sup.3 R.sup.3a, NHC(O)NR.sup.3 R.sup.3a, NHC(S)NR.sup.3 R.sup.3a, NR.sup.3 C(O)OR.sup.3, NR.sup.3 C(O)R.sup.3, SO.sub.2 NR.sup.3 R.sup.3a, SO.sub.2 R.sup.3b, and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S. 24. A compound according to claim 1, wherein R.sup.2 is selected from the group: phenyl substituted with 0-5 R.sup.a, and cyclopropyl or cyclohexyl substituted with 0-2 R.sup.a ; and R.sup.a is independently at each occurrence selected from the group: C.sub.1-4 alkyl, COR.sup.3, CO.sub.2 R.sup.3, and CONR.sup.3 R.sup.3a ; R.sup.3a is H or C.sub.1-4 alkyl. 25. A compound according to claim 1, wherein R.sup.2 is selected from the group: phenyl substituted with 0-5 R.sup.a, and cyclopropyl or cyclohexyl substituted with 0-2 R.sup.a ; R.sup.a is independently at each occurrence selected from the group: C.sub.1-4 alkyl, COR.sup.3, CO.sub.2 R.sup.3, and CONR.sup.3 R.sup.3a ; R.sup.3a is H or C.sub.1-4 alkyl; R.sup.3 is C.sub.1-4 alkyl, C.sub.1-4 alkyl-NR5R5a; and R.sup.5 and R.sup.5a, together with the atoms to which they are attached, form a heterocycle having 4-8 atoms in the ring and containing an additional 0-1 N, S, or O atom. 26. A compound according to claim 1, wherein R.sup.2 is selected from the group: phenyl substituted with 0-5 R.sup.a, and cyclopropyl or cyclohexyl substituted with 0-2 R.sup.a ; R.sup.a is independently at each occurrence selected from the group: C.sub.1-4 alkyl, COR.sup.3, CO.sub.2 R.sup.3, and CONR.sup.3 R.sup.3a ; and R.sup.3a is H or C.sub.1-4 alkyl. 27. A compound according to claim 1, wherein R.sup.2 is phenyl substituted with NR.sup.3 R.sup.3a, wherein R.sup.3 and R.sup.3a, together with the nitrogen atom to which they are attached, form a 4-8 membered heterocycle containing an additional 0-1 N, S, or O atom and substituted with 0-3 R.sup.3c. 28. A compound according to claim 25, wherein R.sup.2 is phenyl substituted with NR.sup.3 R.sup.3a ; and R.sup.3 and R.sup.3a, together with the nitrogen atom to which they are attached, form a pyrrolinyl, pyrrolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, morpholinyl,thiomorpholinyl, homopiperazinyl or piperazinyl group, substituted with 0-3 R.sup.3c. 29. A compound according to claim 25, wherein R.sup.2 is phenyl substituted with NR.sup.3 R.sup.3a, wherein R.sup.3 and R.sup.3a, together with the nitrogen atom to which they are attached, form a piperidinyl, homopiperazinyl or piperazinyl group, substituted with 0-3 R.sup.3c. 30. A compound according to claim 25, wherein R.sup.2 is phenyl substituted with NR.sup.3 R.sup.3a ; and R.sup.3 and R.sup.3a, together with the nitrogen atom to which they are attached, form a piperidinyl, homopiperazinyl or piperazinyl group, substituted with 0-3 substituents independently selected from the group consisting of: --C(.dbd.NH)CH.sub.3, pyrrolinyl, pyrrolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, morpholinyl,thiomorpholinyl, homopiperazinyl or piperazinyl group, pyridyl, C.sub.1-4 alkyl, --NR.sup.3 R.sup.3b. 31. A compound according to claim 1 which is selected from Table 1. 32. A compound according to claim 1 which is selected from Table 2. 33. A compound according to claim 1 which is selected from Table 3. 34. A compound according to claim 1 which is selected from Table 4. 35. A compound according to claim 1, wherein the compound is selected from: 3-(4-methoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-phenyl-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methylthiophenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methanesulfonylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-(N,N-dimethylamino)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(3-pyridyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(formamido)indeno[1,2-c]pyrazol-4-one; 3-(4-hydroxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-piperidinophenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-morpholinophenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-ethoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-butylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-ethylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-n-propylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((4-aminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-pyridyl)-5-(formamido)indeno[1,2-c]pyrazol-4-one; 3-(4-pyridyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((4-aminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((4-azidophenyl)acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((4-(methoxycarbonylamino)phenyl) acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((4-(aminomethylcarbonylamino)phenyl) acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((4-((N,N-dimethylamino)methylcarbonyl amino)phenyl)acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((4-acetamidophenyl)acetamido) indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(pyrrolidinoacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(morpholinoacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(thiomorpholinoacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(ethylaminoacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(piperidinoacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(4-(aminomethyl)piperidinoacetamido) indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(piperazinoacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(4-methylpiperazinoacetamido) indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(4-(2-hydroxyethyl)piperazinoacetamido)indeno[1,2-c]p yrazol-4-one; 3-(4-methoxyphenyl)-5-(N,N-dimethylaminoacetamido)indeno[1,2-c]pyrazol-4-on e; 3-(4-methoxyphenyl)-5-((2-hydroxyethyl)aminoacetamido)indeno[1,2-c]pyrazol- 4-one; 3-(4-methoxyphenyl)-5-(aminoacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((2-chlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one ; 3-(4-methoxyphenyl)-5-((2,4-dichlorophenyl)acetamido)indeno[1,2-c]pyrazol-4 -one; 3-(4-methoxyphenyl)-5-((3',4-dichlorophenyl)acetamido)indeno[1,2-c]pyrazol- 4-one; 3-(4-methoxyphenyl)-5-((2-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-on e; 3-(4-dimethoxyphenyl)-5-(3-thienylacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((3,4-methylenedioxyphenyl)acetamido)indeno[1,2-c]pyr azol-4-one; 3-(3,4-dimethoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(2-methoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((2,5-dimethoxyphenyl)acetamido) indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((3,4-dimethoxyphenyl)acetamido) indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((4-methoxyphenyl)acetamido) indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((3-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-on e; 3-(4-methoxyphenyl)-5-((4-chlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one ; 3-(4-methoxyphenyl)-5-((butylcarbamoyl)amino)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((4-aminobenzylcarbamoyl)amino)indeno [1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((4-pyridylcarbamoyl) amino)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((phenylcarbamoyl)amino)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(cyclobutanecarboxamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(cyclopentanecarboxamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(butanamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(propanamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(phenylacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(2-methylpropanamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(cyclopropanecarboxamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(chloroacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-(4-(aminomethyl)piperidinoacetamido)-indeno[1,2-c]pyr azol-4-one; 3-(4-(N,N-dimethylamino)phenyl)-5-(morpholinoacetamido)indeno[1,2-c]pyrazol -4-one; 3-(4-(N,N-dimethylamino)phenyl)-5-(N,N-dimethylaminoacetamido)indeno[1,2-c] pyrazol-4-one; 3-(4-(trifluoromethyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-(N,N-dimethylamino)phenyl)-5-(4-methyl-piperazinoacetamido)indeno[1,2- c]pyrazol-4-one; 3-(4-(N,N-dimethylamino)phenyl)-5-(4-(aminomethyl)-piperidinoacetamido)inde no[1,2-c]pyrazol-4-one; 3-(4-(N,N-dimethylamino)phenyl)-5-(4-hydroxy-piperidinoacetamido)indeno[1,2 -c]pyrazol-4-one; 3-(4-morpholinophenyl)-5-(morpholinoacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-morpholinophenyl)-5-(4-methylpiperazinoacetamido)indeno[1,2-c]pyrazol- 4-one; 3-(4-morpholinophenyl)-5-(4-hydroxy-piperidinoacetamido)indeno[1,2-c]pyrazo l-4-one; 3-(4-morpholinophenyl)-5-(4-(aminomethyl)-piperidinoacetamido)indeno[1,2-c] pyrazol-4-one; 3-(4-piperazinophenyl)-5-(morpholinoacetamido)indeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((N,N-dimethylamino)acetamido)indeno[1,2-c]pyrazol -4-one; 3-(4-piperazinophenyl)-5-(4-methylpiperazinoacetamido)indeno[1,2-c]pyrazol- 4-one; 3-(4-piperazinophenyl)-5-(4-(aminomethyl)-piperidinoacetamido)indeno[1,2-c] pyrazol-4-one; 3-(4-piperazinophenyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-(aminocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-(morpholinocarbamoylamino)-indeno[1,2-c]pyrazol-4- one; 3-(4-(4-methylpiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]p yrazol-4-one; 3-(4-(4-ethylpiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]py razol-4-one; 3-(4-(4-isopropylpiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2- c]pyrazol-4-one; 3-(4-(4-t-butoxycarbonylpiperazino)phenyl)-5-(morpholinocarbamoylamino)inde no[1,2-c]pyrazol-4-one; 3-(4-(N,N-dimethylamino)phenyl)-5-((4-methylpiperazino)-carbamoylamino)inde no[1,2-c]pyrazol-4-one; 3-(c-propyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(2-thienyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(3-methyl-2-thienyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one; 3-(ethyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(n-propyl)-5-(carbamoylamino)aminoindeno[1,2-c]pyrazol-4-one; 3-(i-propyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(c-propyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(c-hexyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(2-thienyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(3-methyl-2-thienyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-methyl-2-thienyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-carboethoxy-2-thienyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(3-thienyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-methyl-3-pyrrolyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(2,5-dimethyl-3-thienyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(2-furanyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(i-propyl)-5-((N,N-dimethylaminocarbamoyl)amino)indeno[1,2-c]pyrazol-4-on e; 3-(c-propyl)-5-((N,N-dimethylaminocarbamoyl)amino)indeno[1,2-c]pyrazol-4-on e; 3-(c-hexyl)-5-((N,N-dimethylaminocarbamoyl)amino)indeno[1,2-c]pyrazol-4-one ; 3-(2-thienyl)-5-((N,N-dimethylaminocarbamoyl)amino)indeno[1,2-c]pyrazol-4-o ne; 3-(5-methoxy-2-thienyl)-5-((N,N-dimethylaminocarbamoyl)amino)indeno[1,2-c]p yrazol-4-one; 3-(5-methyl-2-thienyl)-5-((N,N-dimethylaminocarbamoyl)amino)indeno[1,2-c]py razol-4-one; 3-(5-carboethoxy-2-thienyl)-5-((N,N-dimethylaminocarbamoyl)amino)indeno[1,2 -c]pyrazol-4-one; 3-(3-thienyl)-5-((N,N-dimethylaminocarbamoyl)amino)indeno[1,2-c]pyrazol-4-o ne; 3-(5-chloro-3-thienyl)-5-((N,N-dimethylaminocarbamoyl)amino)indeno[1,2-c]py razol-4-one; 3-(2,5-dimethyl-3-thienyl)-5-((N,N-dimethylaminocarbamoyl)amino)indeno[1,2- c]pyrazol-4-one; 3-(2-furanyl)-5-((N,N-dimethylaminocarbamoyl)amino)indeno[1,2-c]pyrazol-4-o ne; 3-(i-propyl)-5-((4-carbamoylpiperidino)acetamido)indeno[1,2-c]pyrazol-4-one ; 3-(c-hexyl)-5-((4-carbamoylpiperidino)acetamido)indeno[1,2-c]pyrazol-4-one; 3-(ethyl)-5-(4-(aminomethyl)piperidinoacetamido)indeno[1,2-c]pyrazol-4-one; 3-(i-propyl)-5-(4-(aminomethyl)piperidinoacetamido) indeno[1,2-c]pyrazol-4-one; 3-(c-propyl)-5-(4-(aminomethyl)piperidinoacetamido) indeno[1,2-c]pyrazol-4-one; 3-(c-hexyl)-5-(4-(aminomethyl)piperidinoacetamido) indeno[1,2-c]pyrazol-4-one; 3-(i-propyl)-5-((4-methylpiperazino)carbamoylamino)indeno[1,2-c]pyrazol-4-o ne; 3-(5-carboethoxy-2-thienyl)-5-((4-methylpiperazino)carbamoylamino)indeno[1, 2-c]pyrazol-4-one; 3-(5-carboxyl-2-thienyl)-5-((4-methylpiperazino)carbamoylamino)indeno[1,2-c ]pyrazol-4-one; 3-(2,5-dimethyl-3-thienyl)-5-((4-methylpiperazino)carbamoylamino)indeno[1,2 -c]pyrazol-4-one; 3-(i-propyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-methoxycarbonyl-4-piperidinyl)-5-(morpholinocarbamoylamino)indeno[1,2- c]pyrazol-4-one; 3-(5-methyl-2-thienyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4-o ne; 3-(5-chloro-3-thienyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4-o ne; 3-(2,5-dimethyl-3-thienyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol -4-one; 3-(5-carboethoxy-2-thienyl)-5-(morpholinylcarbamoylamino)indeno[1,2-c]pyraz ol-4-one; 3-(5-carboxyl-2-thienyl)-5-(morpholinylcarbamoylamino)indeno[1,2-c]pyrazol- 4-one; 3-(5-(benzylaminocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamino)indeno[1, 2-c]pyrazol-4-one; 3-(5-((4-methylpiperazino)carbonyl)-2-thienyl)-5-(morpholinocarbamoylamino) indeno[1,2-c]pyrazol-4-one; 3-(5-((2-(1-methyl-2-pyrrolidinyl)ethyl)aminocarbonyl)-2-thienyl)-5-(morpho linocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-((N,N-dimethylamino)aminocarbonyl)-2-thienyl-5-(morpholinocarbamoylami no)indeno[1,2-c]pyrazol-4-one; 3-(5-((2-(N,N-dimethylamino)ethyl)aminocarbonyl)-2-thienyl-5-(morpholinocar bamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(2-pyrrolidinoethyl)aminocarbonyl)-2-thienyl-5-(morpholinocarbamoylami no)indeno [1,2-c]pyrazol-4-one; 3-(5-(2-morpholinoethyl)aminocarbonyl)-2-thienyl)-5-(morpholinocarbamoylami no)indeno[1,2-c]pyrazol-4-one; 3-(5-(morpholinocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamino)indeno[1,2 -c]pyrazol-4-one; 3-(5-((3-(2-pyrrolidon-1-yl)propyl)aminocarbonyl)-2-thienyl-5-(morpholinoca rbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-((2-(3-pyridyl)ethyl)aminocarbonyl)-2-thienyl)-5-(morpholinocarbamoyla mino)indeno[1,2-c]pyrazol-4-one; 3-(5-((3-(1-imidazolyl)propyl)aminocarbonyl)-2-thienyl)-5-(morpholinocarbam oylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-((2-(2-pyridyl)ethyl)aminocarbonyl)-2-thienyl)-5-(morpholinocarbamoyla mino)indeno[1,2-c]pyrazol-4-one; 3-(5-((2-pyridyl)methyl)aminocarbonyl)-2-thienyl)-5-(morpholinocarbamoylami no)indeno[1,2-c]pyrazol-4-one; 3-(5-((2-piperidinoethyl)aminocarbonyl)-2-thienyl)-5-(morpholinocarbamoylam ino)indeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((N,N-dimethylamino)carbamoylamino)indeno[1,2-c]py razol-4-one; 3-(4-(4-methylpiperazino)phenyl)-5-((N,N-dimethylamino)carbamoylamino)inden o[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((4-methylpiperazino)carbamoylamino)-indeno[1,2-c] pyrazol-4-one; 3-(4-(4-methylpiperazino)phenyl)-5-((4-methylpiperazino)carbamoylamino)inde no[1,2-c]pyrazol-4-one; 3-(4-(4-ethylpiperazino)phenyl)-5-((4-methylpiperazino)carbamoylamino)inden o[1,2-c]pyrazol-4-one; 3-(4-(4-isopropylpiperazino)phenyl)-5-((4-methylpiperazino)carbamoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(4-piperazinopheny)-5-((2,6-dimethylpiperidino)carbamoylamino)indeno[1,2- c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((4-(2-hydroxyethyl)piperazino)carbamoylamino)inde no[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((2(R)-(methoxymethyl)pyrrolidino)carbamoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((2(S)-(methoxymethyl)pyrrolidino)carbamoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((2(R)-(1-methoxy-1-methylethyl)pyrrolidino)carbam oylamino)indeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((2(S)-(1-methoxy-1-methylethyl)pyrrolidino)carbam oylamino)indeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((2(R)-(hydroxymethyl)pyrrolidino)carbamoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((2(S)-(hydroxymethyl)pyrrolidino)carbamoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((2(R)-(benzyloxymethyl)pyrrolidino)carbamoylamino )indeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((2(S)-(benzyloxymethyl)pyrrolidino)carbamoylamino )indeno[1,2-c]pyrazol-4-one; 3-(4-(3-methylpiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]p yrazol-4-one; 3-(4-(cis-3,5-dimethylpiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno [1,2-c]pyrazol-4-one; 3-(4-(cis-3,4,5-trimethylpiperazino)phenyl)-5-(morpholinocarbamoylamino)ind eno[1,2-c]pyrazol-4-one; 3-(4-(4-isopropylpiperazino)-2-methylphenyl)-5-(morpholinocarbamoylamino)in deno[1,2-c]pyrazol-4-one; 3-(4-homopiperazinophenyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol -4-one; 3-(4-(4-methylhomopiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2 -c]pyrazol-4-one; 3-(4-(4-ethylhomopiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2- c]pyrazol-4-one; 3-(4-(4-isopropylhomopiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[ 1,2-c]pyrazol-4-one; 3-(4-homopiperazino-2-methylphenyl)-5-(morpholinocarbamoylamino)indeno[1,2- c]pyrazol-4-one; 3-(4-(4-ethylhomopiperazino)-2-methylphenyl)-5-(morpholinocarbamoylamino)in deno[1,2-c]pyrazol-4-one; 3-(4-(4-isopropylhomopiperazino)-2-methylphenyl)-5-(morpholinocarbamoylamin o)indeno[1,2-c]pyrazol-4-one; 3-(4-(4-(N,N-dimethylamino)piperidino)phenyl)-5-(morpholinocarbamoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(4-(4-(N,N-diethylamino)piperidino)phenyl)-5-(morpholinocarbamoylamino)in deno[1,2-c]pyrazol-4-one; 3-(4-(4-piperidinopiperidino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2 -c]pyrazol-4-one; 3-(4-(4-pyrrolidinopiperidino)phenyl)-5-(morpholinocarbamoylamino)indeno[1, 2-c]pyrazol-4-one; 3-(4-(4-(N,N-diethylamino)piperidino)phenyl)-5-(morpholinocarbamoylamino)in deno[1,2-c]pyrazol-4-one; 3-(4-methoxyphenyl)-5-((4-methylpiperazino)-thionocarbamoylamino)indeno[1,2 -c]pyrazol-4-one; 3-(1-methyl-3-pyrrolyl)-5-(carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-pyrrolidinoaminocarbonyl-2-thienyl)-5-(morpholinocarbamoylamino)indeno [1,2-c]pyrazol-4-one; 3-(5-piperidinoaminocarbonyl-2-thienyl)-5-(morpholinocarbamoylamino)indeno[ 1,2-c]pyrazol-4-one; 3-(5-piperidinocarbonyl-2-thienyl)-5-(morpholinocarbamoylamino)indeno[1,2-c ]pyrazol-4-one; 3-(5-piperazinocarbonyl-2-thienyl)-5-(morpholinocarbamoylamino)indeno[1,2-c ]pyrazol-4-one; 3-(5-(4-methylpiperazinocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamino)in deno[1,2-c]pyrazol-4-one; 3-(5-(4-ethylpiperazinocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamino)ind eno[1,2-c]pyrazol-4-one; 3-(5-(4-(2-hydroxyethyl)piperazinocarbonyl)-2-thienyl)-5-(morpholinocarbamo ylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-(cyclopropylmethyl)piperazinocarbonyl)-2-thienyl)-5-(morpholinocarb amoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-(t-butoxycarbonyl)piperazinocarbonyl)-2-thienyl)-5-(morpholinocarba moylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-(2-pyridyl)piperazinocarbonyl)-2-thienyl)-5-(morpholinocarbamoylami no)indeno[1,2-c]pyrazol-4-one; 3-(5-(((1S,4S)-(+)-2,5-diazabicyclo[2.2. 1]heptyl)carbonyl)-2-thienyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyr azol-4-one; 3-(5-(((1S,4S)-(+)-2-methyl-2,5-diazabicyclo[2.2. 1]heptyl)carbonyl)-2-thienyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyr azol-4-one; 3-(5-(4-(N,N-dimethylamino)piperidinocarbonyl)-2-thienyl)-5-(morpholinocarb amoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-pyrrolidinopiperidinocarbonyl)-2-thienyl)-5-(morpholinocarbamoylami no)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-piperidinopiperidinocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamin o)indeno[1,2-c]pyrazol-4-one; 3-(5-cyclohexylaminocarbonyl-2-thienyl)-5-(morpholinocarbamoylamino)indeno[ 1,2-c]pyrazol-4-one; 3-(5-(4-piperidylaminocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamino)inde no[1,2-c]pyrazol-4-one; 3-(5-((1-(t-butoxycarboxyl)piperidin-4-yl)aminocarbonyl)-2-thienyl)-5-(morp holinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-(1-methylpiperidin-4-yl)methylaminocarbonyl)-2-thienyl)-5-(morpholi nocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(3-(N,N-dimethylamino)piperidinocarbonyl)-2-thienyl)-5-(morpholinocarb amoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(3-p-toluenesulfonylamino)piperidinocarbonyl-2-thienyl)-5-(morpholinoc arbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(3-hydroxypiperidinocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(5-((3-piperidyl)aminocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamino)in deno[1,2-c]pyrazol-4-one; 3-(5-((3-quinuclidyl)aminocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamino) indeno[1,2-c]pyrazol-4-one; 3-(5-((3-aminocyclohexyl)aminocarbonyl)-2-thienyl)-5-(morpholinocarbamoylam ino)indeno[1,2-c]pyrazol-4-one; 3-(5-((3-(t-butoxycarbonylamino)cyclohexyl)aminocarbonyl)-2-thienyl)-5-(mor pholinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(2-(N,N-dimethylaminomethyl)piperidinocarbonyl)-2-thienyl)-5-(morpholi nocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(2-(N,N-diethylaminomethyl)piperidinocarbonyl)-2-thienyl)-5-(morpholin ocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-pyrrolidinocarbonyl-2-thienyl)-5-(morpholinocarbamnoylamino) indeno[1,2-c]pyrazol-4-one; 3-(5-(3-aminopyrrolidinocarbonyl)-2-thienyl)-5-(morpholinocarbamnoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(5(3(S)-N-methylamino)pyrrolidinocarbonyl-2-thienyl)-5-(morpholinocarbamo ylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(3(S)-acetamidopyrrolidinocarbonyl)-2-thienyl)-5-(morpholinocarbamoyla mino)indeno[1,2-c]pyrazol-4-one; 3-(5-(3(S)-(N-methylacetamido)pyrrolidinocarbonyl)-2-thienyl)-5-(morpholino carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5(3(S)-(N-methyl-t-butoxycarbonylamino)pyrrolidinocarbonyl)-2-thienyl)-5 -(morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(3-(N,N-dimethylamino)pyrrolidinocarbonyl)-2-thienyl)-5-(morpholinocar bamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(3(R)-(N,N-dimethylamino)pyrrolidinocarbonyl)-2-thienyl)-5-(morpholino carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(3(S)-(N,N-dimethylamino)pyrrolidinocarbonyl)-2-thienyl)-5-(morpholino carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-((1-methylpyrrolidin-3-yl)methylaminocarbonyl)-2-thienyl)-5-(morpholin ocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(2(R)-(pyrrolidinomethyl)pyrrolidinocarbonyl)-2-thienyl)-5-(morpholino carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(2(S)-(hydroxymethyl)pyrrolidinocarbonyl)-2-thienyl)-5-(morpholinocarb amoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(2(R)-(methoxymethyl)pyrrolidinocarbonyl)-2-thienyl)-5-(morpholinocarb amoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(2(S)-(phenylaminomethyl)pyrrolidinocarbonyl)-2-thienyl)-5-(morpholino carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(2(R)-(methoxymethyl)pyrrolidinoaminocarbonyl)-2-thienyl)-5-(morpholin ocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-homopiperidinocarbonyl-2-thienyl)-5-(morpholinocarbamoylamino)indeno[1 ,2-c]pyrazol-4-one; 3-(5-homopiperazinocarbonyl-2-thienyl)-5-(morpholinocarbamoylamino)indeno[1 ,2-c]pyrazol-4-one; 3-(5-(4-methylhomopiperazinocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamin o)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-ethylhomopiperazinocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamino )indeno[1,2-c]pyrazol-4-one; 3-(5-(4-(cyclopropylmethyl)homopiperazinocarbonyl)-2-thienyl)-5-(morpholino carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-(t-butoxycarbonyl)homopiperazinocarbonyl)-2-thienyl)-5-(morpholinoc arbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-acetylhomopiperazinocarbonyl)-2-thienyl)-5-(morpholinocarbamoylamin o)indeno[1,2-c]pyrazol-4-one; 3-(5-((4-methylaminophenyl)aminocarbonyl)-2-thienyl)-5-(morpholinocarbamoyl amino)indeno[1,2-c]pyrazol-4-one; 3-(5-((4-acetamidophenyl)aminocarbonyl)-2-thienyl)-5-(morpholinocarbamoylam ino)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-(diethylamino)phenylaminocarbonyl)-2-thienyl)-5-(morpholinocarbamoy lamino)indeno[1,2-c]pyrazol-4-one; 3-(5-((1-methyl-3-cyclopropylpyrazo-5-yl)aminocarbonyl)-2-thienyl)-5-(morph olinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-methyl-3-pyrrolyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4- one; 3-(5-carboethoxy-2-thienyl)-5-(2(R)-(methoxymethyl)pyrrolidinocarbamoylamin o)indeno[1,2-c]pyrazol-4-one; 3-(5-carboxyl-2-thienyl)-5-(2(R)-(methoxymethyl)pyrrolidinocarbamoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(5-(4-methylpiperazinocarbonyl)-2-thienyl)-5-(2(R)-(methoxymethyl)pyrroli dinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-piperazinocarbonyl-2-thienyl)-5-(2(R)-(methoxymethyl)pyrrolidinocarbam oylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-(t-butoxycarbonyl)piperazinocarbonyl)-2-thienyl)-5-(2(R)-(methoxyme thyl)pyrrolidinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-methylhomopiperazinocarbonyl)-2-thienyl)-5-(2(R)-(methoxymethyl)pyr rolidinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-homopiperazinocarbonyl-2-thienyl)-5-(2(R)-(methoxymethyl)pyrrolidinoca rbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(5-(4-(t-butoxycarbonyl)homopiperazinocarbonyl)-2-thienyl)-5-(2(R)-(metho xymethyl)pyrrolidinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(c-propyl)-5-(4-carbamoylpiperidinoacetamido)indeno[1,2-c]pyrazol-4-one; 3-ethyl-5-(4-methylpiperazinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(c-propyl)-5-(4-methylpiperazinocarbamoylamino)indeno[1,2-c]pyrazol-4-one ; 3-(c-hexyl)-5-(4-methylpiperazinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-ethyl-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(c-propyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(c-hexyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-ethoxycarbonylpiperidin-4-yl)-5-(morpholinocarbamoylamino)indeno[1,2-c ]pyrazol-4-one; 3-(1-phenoxycarbonylpiperidin-4-yl)-5-(morpholinocarbamoylamino)indeno[1,2- c]pyrazol-4-one; 3-(1-(imidazol-1-ylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)ind eno[1,2-c]pyrazol-4-one; 3-(1-(2-thienylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)indeno[ 1,2-c]pyrazol-4-one; 3-(1-carbamoylpiperidin-4-yl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyra zol-4-one; 3-(1-(ethylcarbamoyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)indeno[1,2 -c]pyrazol-4-one; 3-(1-(2-(1-methylpyrrolidin-2-yl) ethylaminocarbamoyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)indeno[1,2 -c]pyrazol-4-one; 3-(1-(4-(dimethylamino)piperidinocarbonyl)piperidin-4-yl)-5-(morpholinocarb amoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(piperazinocarbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)indeno [1,2-c]pyrazol-4-one; 3-(1-(4-(-butoxycarbonyl)piperazinoarbonyl)piperidin-4-yl)-5-(morpholinocar bamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(((1S,4S)-(+)-2,5-diazabicyclo[2.2. 1]hept-2-yl)carbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)indeno[1, 2-c]pyrazol-4-one; 3-(1-(((1S,4S)-(+)-5-methyl-2,5-diazabicyclo[2.2. 1]hept-2-yl)carbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamnino)indeno[1 ,2-c]pyrazol-4-one; 3-(1-(3-aminopropylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)ind eno[1,2-c]pyrazol-4-one; 3-(1-(3-(dimethylamino)propylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoy lamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(3-(t-butoxycarbonylamino)propylcarbonyl)piperidin-4-yl)-5-(morpholino carbamoylainino)indeno[1,2-c]pyrazol-4-one; 3-(1-(4-aminobutylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)inde no[1,2-c]pyrazol-4-one; 3-(1-(4-(dimethylamino)butylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoyl amnino)indeno[1,2-c]pyrazol-4-one; 3-(1-(4-(t-butoxycarbonylamino)butylcarbonyl)piperidin-4-yl)-5-(morpholinoc arbamnoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-((1-methylpiperidin-4-yl)carbonyl)piperidin-4-yl)-5-(morpholinocarbamr oylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-((1-(t-butoxycarbonyl)piperidin-4-yl) carbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol- 4-one; 3-(1-(cis-4-aminocyclohexylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoyla mino)indeno[1,2-c]pyrazol-4-one; 3-(1-(4-aminocyclohexylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino )indeno[1,2-c]pyrazol-4-one; 3(1-(cis-4-(dimethylamino)cyclohexylcarbonyl)piperidin-4-yl)-5-(morpholinoc arbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(4-(t-butoxycarbonylamino)cyclohexylcarbonyl)piperidin-4-yl)-5-(morpho linocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(trans-4-(t-butoxycarbonylamino)cyclohexylcarbonyl)piperidin-4-yl)-5-( morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(piperidin-3-ylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)in deno[1,2-c]pyrazol-4-one; 3-(1-(1-methylpiperidin-3-ylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoyl amino)indeno[1,2-c]pyrazol-4-one; 3-(1-(1-(t-butoxycarbonyl)piperidin-3-ylcarbonyl)piperidin-4-yl)-5-(morphol inocarbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(3-aminocyclohexylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino )indeno[1,2-c]pyrazol-4-one; 3-(1-(3-(dimethylamino)cyclohexylcarbonyl)piperidin-4-yl)-5-(morpholinocarb amoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(trans-4-methoxycyclohexylcarbonyl)piperidin-4-yl)-5-(morpholinocarbam oylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(cis-4-methoxycyclohexylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoy lamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(4-aminobenzylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)ind eno[1,2-c]pyrazol-4-one; 3-(1-(4-(dimethylamino)benzylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoy lamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(4-(t-butoxycarbonylamino)benzylcarbonyl)piperidin-4-yl)-5-(morpholino carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(4-aminophenylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoylamino)ind eno[1,2-c]pyrazol-4-one; 3-(1-(4-(dimethylamino)phenylcarbonyl)piperidin-4-yl)-5-(morpholinocarbamoy lamino)indeno[1,2-c]pyrazol-4-one; 3-(1-(4-(t-butoxycarbonylamino)phenylcarbonyl)piperidin-4-yl)-5-(morpholino carbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(trans-4-carboxylcyclohexyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyr azol-4-one; 3-(trans-4-(methoxycarbonyl)cyclohexyl)-5-(morpholinocarbamoylamino)indeno[ 1,2-c]pyrazol-4-one; 3-(trans-4-(3-(dimethylamino)pyrrolidinocarbonyl)cyclohexyl)-5-(morpholinoc arbamoylamino)indeno[1,2-c]pyrazol-4-one; 3-(trans-4-(piperazinocarbonyl)cyclohexyl)-5-(morpholinocarbamoylamino)inde no[1,2-c]pyrazol-4-one; 3-(trans-4-(4-methylpiperazinocarbonyl)cyclohexyl)-5-(morpholinocarbamoylam ino)indeno[1,2-c]pyrazol-4-one; 3-(trans-4-(homopiperazinocarbonyl)cyclohexyl)-5-(morpholinocarbamoylamino) indeno[1,2-c]pyrazol-4-one; 3-(trans-4-(4-methylhomopiperazinocarbonyl)cyclohexyl)-5-(morpholinocarbamo ylamino)indeno[1,2-c]pyrazol-4-one; or pharmaceutically acceptable salt form thereof. 36. A compound according to claim 1, wherein the compound is selected from: 3-(4-piperazinophenyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4-o ne; 3-(4-(4-methylpiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]p yrazol-4-one; 3-(4-(4-ethylpiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]py razol-4-one; 3-(4-(4-isopropylpiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2- c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((N,N-dimethylamino)carbamoylamino)indeno[1,2-c]py razol-4-one; 3-(4-(4-methylpiperazino)phenyl)-5-((N,N-dimethylamino)-carbamoylamino)inde no[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((4-methylpiperazino)carbamoylamino)indeno[1,2-c]p yrazol-4-one; 3-(4-(4-methylpiperazino)phenyl)-5-((4-methylpiperazino)carbamoylamino)inde no[1,2-c]pyrazol-4-one; 3-(4-(4-ethylpiperazino)phenyl)-5-((4-methylpiperazino)carbamoylamino)inden o[1,2-c]pyrazol-4-one; 3-(4-(4-isopropylpiperazino)phenyl)-5-((4-methylpiperazino)carbamoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((2(R)-(methoxymethyl)pyrrolidino)carbamoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(4-piperazinophenyl)-5-((2(R)-(1-methoxy-1-methylethyl)pyrrolidino)carbam oylamino)indeno[1,2-c]pyrazol-4-one; 3-(4-homopiperazinophenyl)-5-(morpholinocarbamoylamino)-indeno[1,2-c]pyrazo l-4-one; 3-(4-(4-methylhomopiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2 -c]pyrazol-4-one; 3-(4-(4-ethylhomopiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2- c]pyrazol-4-one; 3-(4-(4-isopropylhomopiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[ 1,2-c]pyrazol-4-one; 3-(4-(4-(N,N-dimethylamino)piperidino)phenyl)-5-(morpholinocarbamoylamino)i ndeno[1,2-c]pyrazol-4-one; 3-(4-(4-(N,N-diethylamino)piperidino)phenyl)-5-(morpholinocarbamoylamino)in deno[1,2-c]pyrazol-4-one; 3-(4-(4-piperidinopiperidino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2 -c]pyrazol-4-one; 3-(4-(4-pyrrolidinopiperidino)phenyl)-5-(morpholinocarbamoylamino)indeno[1, 2-c]pyrazol-4-one; or pharmaceutically acceptable salt form thereof. 37. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier, a compound according to claim 1 or a pharmaceutically acceptable salt or prodrug form thereof, and a cytostatic or cytotoxic agent. 38. A method of treating a cell proliferative disease associated with CDK activity in a patient in need thereof,comprising administrering to said patient a pharmaceutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof, wherein the proliferative diseases is selected from the group consisting of: Alzheimer's disease, viral infections, auto-immune diseases, fungal disease, cancer, psoriasis, vascular smooth cell proliferation associated with atherosclerosis, pulmonary fibrosis, arthritis glomerulonephritis, neurodegenerative disorders and post-surgical stenosis and restenosis. 39. A method of treating cancer associated with CDK activity in a patient in need thereof, comprising administrering to said patient a pharmaceutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof, wherein the cancer is selected from the group consisting of: carcinoma; hematopoietic tumors of lymphoid lineage; hematopoietic tumors of myeloid lineage; tumors of mesenchymal origin, tumors of the central and peripheral nervous system, melanoma, seminoma, teratocarcinoma, osteosarcoma, xenoderoma pigmentosum, keratoctanthoma, thyroid follicular cancer and Kaposi's sarcoma. 40. A method of treating a disease associated with apoptosis in a patient in need thereof, comprising administrering to said patient a pharmaceutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof, wherein the disease associated with apoptosis is selected from the group consisting of: cancer, viral infections, autoimmune diseases and neurodegenerative disorder. 41. A method of inhibiting tumor angiogenesis and metastasis in a patient in need thereof, comprising administrering to said patient a pharmaceutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 42. A method of modulating the level of cellular RNA and DNA synthesis in a patient in need thereof, comprising administering to said patient a CDK inhibitory effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 43. A method of treating viral infections in a patient in need thereof, comprising administering to said patient a CDK inhibitory effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof, wherein the viral infections is selected from the group consiting of HIV, human papilloma virus, herpesvirus, poxyirus, Epstein-Barr virus, Sindbis virus and adenovirus. 44. A method of chemopreventing cancer in a patient, comprising administering to said patient in need thereof, a CDK inhibitory effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 45. A method of inhibiting CDK activity comprising combining an effective amount of a compound according to claim 1, with a composition containing CDK. 46. A method of treating cancer associated with CDK activity in a patient in need thereof, comprising administrering to said patient a pharmaceutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof, in combination (administered together or sequentially) with known anti-cancer treatments. 47. A method treating cell proliferative diseases associated with CDK activity in a patient in need thereof, comprising administrering to said patient a pharmaceutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof, in combination (administered together or sequentially) with known anti-proliferating agents selected from the group consisting of:, altretamine, busulfan, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, thiotepa, cladribine, fluorouracil, floxuridine, gemcitabine, thioguanine, pentostatin, methotrexate, 6-mercaptopurine, cytarabine, carmustine, lomustine, streptozotocin, carboplatin, cisplatin, oxaliplatin, iproplatin, tetraplatin, lobaplatin, JM216, JM335, fludarabine, aminoglutethimide, flutamide, goserelin, leuprolide, megestrol acetate, cyproterone acetate, tamoxifen, anastrozole, bicalutamide, dexamethasone, diethylstilbestrol, prednisone, bleomycin, dactinomycin, daunorubicin, doxirubicin, idarubicin, mitoxantrone, losoxantrone, mitomycin-c, plicamycin, paclitaxel, docetaxel, CPT-11, epothilones , topotecan, irinotecan, 9-amino camptothecan, 9-nitro camptothecan, GS-211, etoposide, teniposide, vinblastine, vincristine, vinorelbine, procarbazine, asparaginase, pegaspargase, methoxtrexate, octreotide, estramustine, and hydroxyurea. 48. A method of inhibiting CDKl activity, comprising adminsitering to a patient in need thereof an efective CDK1 inhibitory amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 49. A method of inhibiting CDK2 activity, comprising adminsitering to a patient in need thereof an efective CDK2 inhibitory amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 50. A method of inhibiting CDK3 activity, comprising adminsitering to a patient in need thereof an efective CDK3 inhibitory amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 51. A method of inhibiting CDK4 activity, comprising adminsitering to a patient in need thereof an efective CDK4 inhibitory amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 52. A method of inhibiting CDK5 activity, comprising adminsitering to a patient in need thereof an efective CDK5 inhibitory amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 53. A method of inhibiting CDK6 activity, comprising adminsitering to a patient in need thereof an efective CDK6 inhibitory amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 54. A method of inhibiting CDK7 activity, comprising adminsitering to a patient in need thereof an efective CDK7 inhibitory amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 55. A method of inhibiting CDK8 activity, comprising adminsitering to a patient in need thereof, an efective CDK8 inhibitory amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 56. A method of inhibiting CDK9 activity, comprising adminsitering to a patient in need thereof an efective CDK9 inhibitory amount of a compound according to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof. 57. A pharmaceutical kit for treating a cell proliferative disease associated with CDK activity, said kit comprising a plurality of separate containers, wherein at least one of said containers contains a compound accordig to claim 1, or a pharmaceutically acceptable salt or prodrug form thereof, and at least another of said containers contains one or more compounds selected from the group consisting of cytostatic or cytotoxic agents; topoisomerase II inhibitors; topoisomerase I inhibitors tubulin interacting agents; hormonal agents; thymidilate synthase inhibitors; and anti-metabolites, and said containers optionally contain a pharmaceutical carrier, which kit may be effectively utilized for carrying out combination therapies according to the invention.

Details for Patent 6,407,103

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2018-04-21
Servier Pharmaceuticals Llc	ONCASPAR	pegaspargase	Injection	103411	02/01/1994		2018-04-21