Claims for Patent: 9,957,276

Summary for Patent: 9,957,276

Title:	CDK inhibitors
Abstract:	Compounds of formulae I, II or III, and pharmaceutically acceptable salts thereof, are useful as CDK inhibitors.
Inventor(s):	Tavares; Francis X. (Durham, NC), Strum; Jay C. (Hillsborough, NC)
Assignee:	GI Therapeutics, Inc. (Research Triangle Park, NC)
Application Number:	15/348,770
Patent Claims:	1. A compound of formula: ##STR00209## or a pharmaceutically acceptable salt thereof, wherein: Z is --(CH.sub.2).sub.x-- wherein x is 2 or 3; each X is independently CH or N; each R.sup.1 is independently aryl, alkyl, or cycloalkyl, wherein two R.sup.1s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached optionally form a 3-8-membered cycle; y is 0, 1, 2, or 3; R.sup.2 is -(alkylene).sub.m-heterocyclo, -(alkylene).sub.m-heteroaryl, -(alkylene).sub.m-NR.sup.3R.sup.4, -(alkylene).sub.m-C(O)--NR.sup.3R.sup.4, -(alkylene).sub.m-C(O)--O-alkyl, -(alkylene).sub.m-O--R.sup.5, -(alkylene).sub.m-S(O).sub.n--R.sup.5, or -(alkylene).sub.m-S(O).sub.n--NR.sup.3R.sup.4 any of which may be optionally independently substituted with one or more R.sup.x groups as allowed by valence; m is 0 or 1; n is 1 or 2; R.sup.3 and R.sup.4 at each occurrence are independently: (i) hydrogen or (ii) alkyl, cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, or heteroarylalkyl, or R.sup.3 and R.sup.4 together with the nitrogen atom to which they are attached may combine to form a heterocyclo ring; R.sup.5 is: (i) hydrogen or (ii) alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, or heteroarylalkyl; R.sup.x at each occurrence is independently, halo, cyano, nitro, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkyl; and R.sup.6 is a lower alkyl or absent. 2. The compound of claim 1 having formula: ##STR00210## or a pharmaceutically acceptable salt thereof. 3. The compound of claim 1 having formula: ##STR00211## or a pharmaceutically acceptable salt thereof. 4. The compound of claim 1 having formula: ##STR00212## or a pharmaceutically acceptable salt thereof. 5. The compound of claim 1 having formula: ##STR00213## or a pharmaceutically acceptable salt thereof. 6. The compound of claim 1 having formula: ##STR00214## or a pharmaceutically acceptable salt thereof. 7. The compound of claim 1 having formula: ##STR00215## or a pharmaceutically acceptable salt thereof. 8. The compound of claim 1 having formula: ##STR00216## or a pharmaceutically acceptable salt thereof. 9. The compound of claim 1 having formula: ##STR00217## or a pharmaceutically acceptable salt thereof. 10. The compound of claim 1 having formula: ##STR00218## or a pharmaceutically acceptable salt thereof. 11. The compound of claim 1 having formula: ##STR00219## or a pharmaceutically acceptable salt thereof. 12. The compound of claim 1, wherein x 2. 13. The compound of claim 1, wherein y is 0, 1, or 2. 14. The compound of claim 1, wherein R.sup.2 is -(alkylene).sub.m-heterocyclo, -(alkylene).sub.m-NR.sup.3R.sup.4, -(alkylene).sub.m-C(O)--NR.sup.3R.sup.4; -(alkylene).sub.m-C(O)--O-alkyl, or -(alkylene).sub.m-O--R.sup.5. 15. The compound of claim 1, wherein R.sup.2 is -(alkylene).sub.m-heterocyclo or -(alkylene).sub.m-heteroaryl. 16. The compound of claim 1, wherein R.sup.2 is -(alkylene).sub.m-heterocyclo. 17. The compound of claim 16, wherein m is 0. 18. The compound of claim 1, wherein R.sup.2 is substituted with one R.sup.x group. 19. The compound of claim 1, wherein R.sup.x is selected from alkyl, cycloalkyl, and heterocyclo. 20. The compound of claim 1, wherein R.sup.6 is absent. 21. The compound of claim 1, wherein both of X are N. 22. The compound of claim 1, wherein one X is N and the other is CH. 23. The compound of claim 22, wherein x is 2. 24. The compound of claim 23, wherein y is 0, 1, or 2. 25. The compound of claim 24, wherein R.sup.2 is -(alkylene).sub.m-heterocyclo. 26. The compound of claim 25, wherein m is 0. 27. The compound of claim 26, wherein R.sup.2 is substituted with one R.sup.x group. 28. The compound of claim 27, wherein R.sup.x is selected from alkyl, cycloalkyl, and heterocyclo. 29. The compound of claim 28, wherein R.sup.6 is absent. 30. The compound of claim 29, wherein y is 2. 31. The compound of claim 30, wherein two R.sup.1s on the same ring atom together with the ring atom to which they are attached form a 3-8-membered cycle. 32. The compound of claim 31, wherein the 3-8-membered cycle is a 6-membered cycle. 33. A compound of formula: ##STR00220## or a pharmaceutically acceptable salt thereof, wherein: Z is --(CH.sub.2).sub.x-- wherein x is 2 or 3; each X is independently CH or N; each R.sup.1 is independently aryl, alkyl, or cycloalkyl, wherein two R.sup.1s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached optionally form a 3-8-membered cycle; y is 0, 1, 2, or 3; R.sup.6 is a lower alkyl or absent; R.sup.2 is ##STR00221## R.sup.2* is a bond, alkylene, -(alkylene).sub.m-O-(alkylene).sub.m-, -(alkylene).sub.m-C(O)-(alkylene).sub.m-, -(alkylene).sub.m-S(O).sub.2-(alkylene).sub.m- or -(alkylene).sub.m-NH-(alkylene).sub.m-; P is a 4- to 8-membered mono- or bicyclic saturated heterocyclyl group; each R.sup.x1 is independently --(C(O))--O-alkyl, -(alkylene).sub.m-cycloalkyl, --N(R.sup.N)-cycloalkyl, --C(O)-cycloalkyl, -(alkylene).sub.m-heterocyclyl, --N(R.sup.N)-heterocyclyl, --C(O)-heterocyclyl, or --S(O).sub.2-(alkylene).sub.m; R.sup.N is H, C.sub.1 to C.sub.4 alkyl or C.sub.1 to C.sub.6 heteroalkyl; m is 0 or 1; and t is 0, 1 or 2. 34. The compound of claim 33, wherein x is 2. 35. The compound of claim 33, wherein y is 0, 1, or 2. 36. The compound of claim 33, wherein R.sup.6 is absent. 37. The compound of claim 33, wherein one X is N and the other is CH. 38. The compound of claim 37, wherein x is 2. 39. The compound of claim 38, wherein y is 0, 1, or 2. 40. The compound of claim 39, wherein R.sup.6 is absent. 41. The compound of claim 40, wherein y is 2. 42. The compound of claim 41, wherein two R.sup.1s on the same ring atom together with the ring atom to which they are attached form a 3-8-membered cycle. 43. The compound of claim 42, wherein the 3-8-membered cycle is a 6-membered cycle. 44. The compound of claim 43, wherein R.sup.2 is ##STR00222## 45. The compound of claim 43, wherein R.sup.2 is ##STR00223## 46. A compound of formula: ##STR00224## or a pharmaceutically acceptable salt thereof, wherein: Z is --(CH.sub.2).sub.x-- wherein x is 2 or 3; each X is independently CH or N; each R.sup.1 is independently aryl, alkyl, or cycloalkyl, wherein two R.sup.1s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached optionally form a 3-8-membered cycle; y is 0, 1, 2, or 3; R.sup.6 is a lower alkyl or absent; R.sup.2 is ##STR00225## R.sup.2* is a bond, alkylene, -(alkylene).sub.m-O-(alkylene).sub.m-, -(alkylene).sub.m-C(O)-(alkylene).sub.m-, -(alkylene).sub.m-S(O).sub.2-(alkylene).sub.m- or -(alkylene).sub.m-NH-(alkylene).sub.m-; P is a 4- to 8-membered mono- or bicyclic saturated heterocyclyl group; P1 is a 4- to 6-membered monocyclic saturated heterocyclyl group; each R.sup.x2 is independently hydrogen or alkyl; m is 0 or 1; and s is 0, 1 or 2. 47. The compound of claim 46, wherein x is 2. 48. The compound of claim 46, wherein y is 0, 1, or 2. 49. The compound of claim 46, wherein R.sup.6 is absent. 50. The compound of claim 46, wherein one X is N and the other is CH. 51. The compound of claim 50, wherein x is 2. 52. The compound of claim 51, wherein y is 0, 1, or 2. 53. The compound of claim 52, wherein R.sup.6 is absent. 54. The compound of claim 53, wherein y is 2. 55. The compound of claim 54, wherein two R.sup.1s on the same ring atom together with the ring atom to which they are attached form a 3-8-membered cycle. 56. The compound of claim 55, wherein the 3-8-membered cycle is a 6-membered cycle. 57. The compound of claim 56, wherein R.sup.2 is ##STR00226##