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):	Francis X. Tavares, Jay C. Strum
Assignee:	Pharmacosmos Holding AS, Pharmacosmos AS, Gi Therapeutics Inc
Application Number:	US15/348,770
Patent Claims:	1. A compound of formula: or a pharmaceutically acceptable salt thereof, wherein: Z is —(CH2)x— wherein x is 2 or 3; each X is independently CH or N; each R1 is independently aryl, alkyl, or cycloalkyl, wherein two R1s 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; R2 is -(alkylene)m-heterocyclo, -(alkylene)m-heteroaryl, -(alkylene)m-NR3R4, -(alkylene)m-C(O)—NR3R4, -(alkylene)m-C(O)—O-alkyl, -(alkylene)m-O—R5, -(alkylene)m-S(O)n—R5, or -(alkylene)m-S(O)n—NR3R4 any of which may be optionally independently substituted with one or more Rx groups as allowed by valence; m is 0 or 1; n is 1 or 2; R3 and R4 at each occurrence are independently: (i) hydrogen or (ii) alkyl, cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, or heteroarylalkyl, or R3 and R4 together with the nitrogen atom to which they are attached may combine to form a heterocyclo ring; R5 is: (i) hydrogen or (ii) alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, or heteroarylalkyl; Rx at each occurrence is independently, halo, cyano, nitro, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkyl; and R6 is a lower alkyl or absent. 2. The compound of claim 1 having formula: or a pharmaceutically acceptable salt thereof. 3. The compound of claim 1 having formula: or a pharmaceutically acceptable salt thereof. 4. The compound of claim 1 having formula: or a pharmaceutically acceptable salt thereof. 5. The compound of claim 1 having formula: or a pharmaceutically acceptable salt thereof. 6. The compound of claim 1 having formula: or a pharmaceutically acceptable salt thereof. 7. The compound of claim 1 having formula: or a pharmaceutically acceptable salt thereof. 8. The compound of claim 1 having formula: or a pharmaceutically acceptable salt thereof. 9. The compound of claim 1 having formula: or a pharmaceutically acceptable salt thereof. 10. The compound of claim 1 having formula: or a pharmaceutically acceptable salt thereof. 11. The compound of claim 1 having formula: 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 R2 is -(alkylene)m-heterocyclo, -(alkylene)m-NR3R4, -(alkylene)m-C(O)—NR3R4; -(alkylene)m-C(O)—O-alkyl, or -(alkylene)m-O—R5. 15. The compound of claim 1, wherein R2 is -(alkylene)m-heterocyclo or -(alkylene)m-heteroaryl. 16. The compound of claim 1, wherein R2 is -(alkylene)m-heterocyclo. 17. The compound of claim 16, wherein m is 0. 18. The compound of claim 1, wherein R2 is substituted with one Rx group. 19. The compound of claim 1, wherein Rx is selected from alkyl, cycloalkyl, and heterocyclo. 20. The compound of claim 1, wherein R6 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 R2 is -(alkylene)m-heterocyclo. 26. The compound of claim 25, wherein m is 0. 27. The compound of claim 26, wherein R2 is substituted with one Rx group. 28. The compound of claim 27, wherein Rx is selected from alkyl, cycloalkyl, and heterocyclo. 29. The compound of claim 28, wherein R6 is absent. 30. The compound of claim 29, wherein y is 2. 31. The compound of claim 30, wherein two R1s 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: or a pharmaceutically acceptable salt thereof, wherein: Z is —(CH2)x— wherein x is 2 or 3; each X is independently CH or N; each R1 is independently aryl, alkyl, or cycloalkyl, wherein two R1s 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; R6 is a lower alkyl or absent; R2 is R2* is a bond, alkylene, -(alkylene)m-O-(alkylene)m-, -(alkylene)m-C(O)-(alkylene)m-, -(alkylene)m-S(O)2-(alkylene)m- or -(alkylene)m-NH-(alkylene)m-; P is a 4- to 8-membered mono- or bicyclic saturated heterocyclyl group; each Rx1 is independently —(C(O))—O-alkyl, -(alkylene)m-cycloalkyl, —N(RN)-cycloalkyl, —C(O)-cycloalkyl, -(alkylene)m-heterocyclyl, —N(RN)-heterocyclyl, —C(O)-heterocyclyl, or —S(O)2-(alkylene)m; RN is H, C1 to C4 alkyl or C1 to C6 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 R6 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 R6 is absent. 41. The compound of claim 40, wherein y is 2. 42. The compound of claim 41, wherein two R1s 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 R2 is 45. The compound of claim 43, wherein R2 is 46. A compound of formula: or a pharmaceutically acceptable salt thereof, wherein: Z is —(CH2)x— wherein x is 2 or 3; each X is independently CH or N; each R1 is independently aryl, alkyl, or cycloalkyl, wherein two R1s 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; R6 is a lower alkyl or absent; R2 is R2* is a bond, alkylene, -(alkylene)m-O-(alkylene)m-, -(alkylene)m-C(O)-(alkylene)m-, -(alkylene)m-S(O)2-(alkylene)m- or -(alkylene)m-NH-(alkylene)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 Rx2 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 R6 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 R6 is absent. 54. The compound of claim 53, wherein y is 2. 55. The compound of claim 54, wherein two R1s 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 R2 is