Claims
- 1. A compound of the Formula I:
- 2. A compound, pharmaceutically acceptable salt, prodrug, or pharmaceutically active metabolite thereof according to claim 1, wherein: when R1 is substituted, each substituent independently is a halogen, haloalkyl, C1-6-alkyl, C1-6-alkenyl, C1-6-alkynyl, hydroxyl, oxygen, C1-6-alkoxyl, amino, nitro, thiol, thioether, imine, cyano, amido, phosphonato, phosphine, carboxyl, thiocarbonyl, sulfonyl, sulfonamide, ketone, aldehyde, or ester; and each substituent of R2 independently is a halogen, haloalkyl, C1-6-alkyl, C1-6-alkenyl, C1-6-alkynyl, hydroxyl, C1-6-alkoxyl, amino, nitro, thiol, thioether, imine, cyano, amido, phosphonato, phosphine, carboxyl, thiocarbonyl, sulfonyl, sulfonamide, ketone, aldehyde, or ester.
- 3. A compound, pharmaceutically acceptable salt, prodrug, or active metabolite according to claim 1, wherein R1 is a substituted phenyl group.
- 4. A compound, pharmaceutically acceptable salt, prodrug, or active metabolite according to claim 1, wherein R1 is phenyl substituted with an alkylamine or pyridine group.
- 5. A compound, pharmaceutically acceptable salt, prodrug, or active metabolite according to claim 1, wherein R1 is selected from the group consisting of:
- 6. A compound, pharmaceutically acceptable salt, prodrug, or active metabolite according to claim 1, wherein R1 is phenyl substituted by optionally substituted carbonyl or sulfonamide.
- 7. A compound, pharmaceutically acceptable salt, prodrug, or active metabolite according to claim 1, wherein R1 is selected from the group consisting of:
- 8. A compound, pharmaceutically acceptable salt, prodrug or active metabolite according to claim 1, wherein R2 is ortho-substituted phenyl or thienyl.
- 9. A compound, pharmaceutically acceptable salt, prodrug or active metabolite according to claim 9, wherein R2 is o-halophenyl or o-dihalophenyl.
- 10. A compound, pharmaceutically acceptable salt, prodrug or active metabolite according to claim 10, wherein R2 is o-difluorophenyl.
- 11. A compound according to claim 1 selected from the group consisting of:
- 12. A compound according to claim 1 selected from the group consisting of:
- 13. A compound selected from the group consisting of:
- 14. A pharmaceutical composition comprising:
(a) an amount of a cell-cycle control agent effective to inhibit CDK4 or a CDK4/cyclin complex, said cell-cycle control agent being selected from the group consisting of:
(i) a compound of the Formula I: 518 wherein:
R1 is a substituted or unsubstituted group selected from: C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; C1-6-alkoxyl; C1-6-alcohol; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; carbonyl; ether; (C1-6-alkyl)-carbonyl; (C1-6-alkyl)-aryl; (C1-6-alkyl)-cycloalkyl; (C1-6-alkyl)-(C1-6-alkoxyl); aryl-(C1-6-alkoxyl); thioether; thiol; and sulfonyl; wherein when R1 is substituted, each substituent independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; and R2 is a carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, ring structure having a substituent at the position adjacent to the point of attachment, which ring structure is optionally further substituted, where each substituent of R2 independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; (ii) a pharmaceutically acceptable salt of a compound of the Formula I; and (iii) a prodrug or pharmaceutically active metabolite of a compound of the Formula I or a pharmaceutically acceptable salt thereof; and (b) a pharmaceutically acceptable carrier.
- 15. A method of treating a disease or disorder mediated by inhibition of CDK4 or a CDK4/cyclin complex, comprising administering to a subject in need of such treatment a cell-cycle control agent selected from the group consisting of:
compounds of the Formula I: 519 wherein:
R1 is a substituted or unsubstituted group selected from: C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; C1-6-alkoxyl; C1-6-alcohol; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; carbonyl; ether; (C1-6-alkyl)-carbonyl; (C1-6-alkyl)-aryl; (C1-6-alkyl)-cycloalkyl; (C1-6-alkyl)-(C1-6-alkoxyl); aryl-(C1-6-alkoxyl); thioether; thiol; and sulfonyl; wherein when R1 is substituted, each substituent independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; oxygen; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; or ester; and R2 is a carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, ring structure having a substituent at the position adjacent the point of attachment, which ring structure is optionally further substituted, where each substituent of R2 independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; or ester; pharmaceutically acceptable salts of compounds of the Formula I; and prodrugs and pharmaceutically active metabolites of compounds of the Formula I and their pharmaceutically acceptable salts.
- 16. A compound of the Formula I:
- 17. A pharmaceutical composition comprising:
(a) an effective amount for inhibiting a CDK or a CDK/cyclin complex of a cell-cycle control agent selected from:
(i) compounds of the Formula I: 522 wherein:
R1 is selected from: 523R2 is a substituted or unsubstituted: carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, ring structure; where each optional substituent for R2 is independently a halogen; oxygen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; or ester; (ii) pharmaceutically acceptable salts of compounds of the Formula I; and (iii) prodrugs and pharmaceutically active metabolites of compounds of the Formula I or pharmaceutically acceptable salts thereof; and (b) a pharmaceutically acceptable carrier.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This regular application claims priority to U.S. Provisional Application No. 60/063,634, filed Oct. 27, 1997, and U.S. Provisional Application No. 60/063,666, filed Oct. 28, 1997.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60063634 |
Oct 1997 |
US |
|
60063666 |
Oct 1997 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09179744 |
Oct 1998 |
US |
Child |
10388851 |
Mar 2003 |
US |