Claims for Patent: RE50455

Summary for Patent: RE50455

Title:	Pyrazolopyridine derivative having GLP-1 receptor agonist effect
Abstract:	The present invention provides a compound having the basic structure shown by Formula (I) in which the indole ring and the pyrazolopyridine structure is bound through a substituent, a salt thereof or a solvate of either the compound or a salt of the compound, as well as a preventative agent or a therapeutic agent for non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity containing such compound, salt or solvate as an active ingredient.
Inventor(s):	Hitoshi Yoshino, Satoshi Tsuchiya, Atsushi Matsuo, Tsutomu Sato, Masahiro Nishimoto, Kyoko OGURI, Hiroko Ogawa, Yoshikazu Nishimura, Yoshiyuki Furuta, Hirotaka Kashiwagi, Nobuyuki Hori, Takuma Kamon, Takuya Shiraishi, Shoshin YOSHIDA, Takahiro Kawai, Satoshi Tanida, Masahide Aoki
Assignee:	Chugai Pharmaceutical Co Ltd
Application Number:	US18/077,060
Patent Claims:	1. A compound represented by Formula (I): wherein, X is —N═ or —CRa═; Ra is selected from a hydrogen atom, a halogen atom, and C1-6 alkyl; Y is selected from —C(═O)—, —CHR—, and —S(═O)2—; R is a hydrogen atom or C1-6 alkyl; Q1 is C6-10 aryl or 5 to 10 membered heteroaryl, wherein C6-10 aryl and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from a halogen atom, C1-6 alkyl (wherein C1-6 alkyl is optionally substituted with one or more halogen atoms), and C1-6 alkoxy; Q2 is 3 to 12 membered heterocyclyl or 5 to 10 membered heteroaryl, wherein 3 to 12 membered heterocyclyl and 5 to 10 membered heteroaryl are optionally substituted with one to three substituents independently selected from a halogen atom, C1-6 alkyl (wherein C1-6 alkyl is optionally substituted with one or more halogen atoms), C1-6 alkoxy, and —NRQaRQb, and two C1-6 alkyl groups together with a carbon atom to which they are attached may form C3-8 carbocyclic ring; and RQa and RQb are independently selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; R1, R2 and R3 are each independently selected from a hydrogen atom and C1-6 alkyl (wherein, C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, C1-6 alkoxy, and hydroxy); R4, R5 and R6 are independently selected from a hydrogen atom, a halogen atom, and C1-6 alkyl; R7 and R8 are independently a hydrogen atom or C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom and C3-15 cycloalkyl, or R7 and R8 together with a carbon atom to which they are attached may form C3-15 cycloalkane ring, wherein C3-15 cycloalkane ring formed by R7 and R8 together is optionally substituted with one to three C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, hydroxy, —NR7aR7b, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, and R7a and R7b are independently selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; n1 is an integer of 0 to 3; n2 is an integer of 0 to 5; R9 is selected from the group consisting of —CO2R9f, and —C(═O)—NR9gR9h; R9a, R9b, R9c, R9d, and R9g are each independently selected from a hydrogen atom, C1-6 alkyl (wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom and C1-6 alkoxy), and (C1-6 alkyl)carbonyl; R9e is a hydrogen atom, or C1-6 alkyl that is optionally substituted with one or more halogen atoms; R9f is a hydrogen atom or C1-6 alkyl; R9h is a hydrogen atom, C1-6 alkyl, (C1-6 alkyl)carbonyl, cyano, or —S(═O)n3—R9i; n3 is an integer of 0 to 2; and R9i is C1-6 alkyl; Z1 is selected from the group consisting of wherein Rza is selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; Rzb and Rzc are independently a hydrogen atom or C1-6 alkyl; n4 is an integer of 1 to 3; n5 and n6 are independently an integer of 0 to 10 (* represents a binding position with a pyrazolopyridine structure, and ** represents a binding position with Z2); Z2 is selected from the group consisting of C1-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10 aryl and 5 to 10 membered heteroaryl, wherein C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10 aryl, and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from Group A: Group A: a) oxo, b) a halogen atom, c) cyano, d) —NRzdRze; wherein Rzd and Rze are independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and C1-6 alkoxy, e) —C(═O)—NRzfRzg; wherein Rzf and Rzg are independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and C1-6 alkoxy, f) —S(═O)n7—Rzh; wherein n7 is an integer of 0 to 2; and Rzh is a hydrogen atom or C1-6 alkyl, g) C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, —NRziRzj, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rzi and Rzj are independently a hydrogen atom or C1-6 alkyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from hydroxy, C1-6 alkyl and 3 to 12 membered heterocyclyl, h) C1-6 alkoxy; wherein C1-6 alkoxy is optionally substituted with one or more substituent independently selected from hydroxy, a halogen atom, and C1-6 alkoxy, i) 3 to 12 membered heterocyclyl; wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from C1-6 alkyl and (C1-6 alkyl)carbonyl, j) C6-10 aryl; wherein C6-10 aryl is optionally substituted with one or more (C1-6 alkyl)carbonyl, and k) 5 to 10 membered heteroaryl; wherein 5 to 10 membered heteroaryl is optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, —NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzk and Rzl are independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from C1-6 alkyl and (C1-6 alkyl)carbonyl; or a salt thereof. 2. The compound according to claim 1, or a salt thereof, wherein Q1 is phenyl or pyridyl, and phenyl or pyridyl is substituted with one to four substituents independently selected from a halogen atom and C1-6 alkyl. 3. The compound according to claim 2, or a salt thereof, wherein R7 and R8 are both a hydrogen atom; R7 and R8 are both C1-6 alkyl; R7 is a hydrogen atom and R8 is C1-6 alkyl; or R7 and R8 together with a carbon atom to which they are attached form C3-8 cycloalkane ring, wherein C3-8 cycloalkyl formed is optionally substituted with one to two C1-6 alkyl, and C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, C1-6 alkoxy, and 3 to 12 membered heterocyclyl. 4. The compound according to claim 3 or a salt thereof, wherein Z2 is selected from C1-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10 aryl, and 5 to 10 membered heteroaryl, wherein C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10 aryl, and 5 to 10 membered heteroaryl are optionally substituted with one to four substituents independently selected from Group B: Group B: a) oxo, b) a halogen atom, c) —NRzd1Rze1; wherein Rzd1 and Rze1 are independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, and C1-6 alkyl is optionally substituted with one or more C1-6 alkoxy, d) —S(═O)n7—Rzh1; wherein n7 is an integer of 0 to 2, Rzh1 is C1-6 alkyl, e) C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, hydroxy, —NRziRzj, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rzi and Rzj are independently a hydrogen atom or C1-6 alkyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from hydroxy, C1-6 alkyl and 3 to 12 membered heterocyclyl, f) C1-6 alkoxy; wherein C1-6 alkoxy is optionally substituted with one or more hydroxy, g) 3 to 12 membered heterocyclyl; wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more (C1-6 alkyl)carbonyl, h) 5 to 10 membered heteroaryl; wherein 5 to 10 membered heteroaryl is optionally substituted with one or more substituents independently selected from C1-6 alkyl, and —NRzk1Rzl1; and Rzk1 and Rzl1 are independently selected from a hydrogen atom and C1-6 alkyl. 5. The compound according to claim 4, or a salt thereof, wherein Y is —C(═O)—. 6. The compound according to claim 5, or a salt thereof, wherein R1 is a hydrogen atom. 7. The compound according to claim 6, or a salt thereof, wherein n1 and n2 are both 0. 8. The compound according to claim 7, or a salt thereof, wherein R9 is the Formula 9. The compound according to claim 8, or a salt thereof, wherein X is —N═, —CH═, or —CF═. 10. The compound according to claim 9, or a salt thereof, wherein Z1 is the Formula: wherein * represents a binding position with a pyrazolopyridine structure, and ** represents a binding position with Z2. 11. A pharmaceutical composition comprising the compound according to claim 10, or a salt thereof, as an active ingredient. 12. A method for treating non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity comprising administering an effective amount of the compound according to claim 1, or a salt thereof, as an active ingredient to a patient in need of such treatment. 13. The compound according to claim 1, or a salt thereof, represented by the formula: 14. The compound according to claim 13, or a salt thereof, of the formula: 15. The hemicalcium salt hydrate of the compound according to claim 14. 16. A pharmaceutical composition comprising the compound according to claim 14 or, a salt thereof, or of claim 15 as an active ingredient. 17. A method for treating non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity in a patient in need thereof, comprising administering an effective amount of a compound according to claim 14 or a salt thereof, or of claim 15. 18. A compound selected from: or a mixture thereof, or a salt thereof. 19. A compound of the formula: or a salt thereof. 20. A compound of the formula: 21. A hemicalcium salt hydrate compound of: 22. A pharmaceutical composition comprising the compound according to claim 18. 23. A pharmaceutical composition comprising the compound according to claim 18 and a pharmaceutically acceptable additive. 24. A method for treating non-insulin-dependent diabetes mellitus (Type 2 diabetes) in a patient in need thereof, comprising administering an effective amount of the compound according to claim 18. 25. A method for treating obesity in a patient in need thereof, comprising administering an effective amount of the compound according to claim 18. 26. A method for treating hyperglycemia in a patient in need thereof, comprising administering an effective amount of the compound according to claim 18. 27. A pharmaceutical composition comprising the compound according to claim 19. 28. A pharmaceutical composition comprising the compound according to claim 19 and a pharmaceutically acceptable additive. 29. A method for treating non-insulin-dependent diabetes mellitus (Type 2 diabetes) in a patient in need thereof, comprising administering an effective amount of the compound according to claim 19. 30. A method for treating obesity in a patient in need thereof, comprising administering an effective amount of the compound according to claim 19. 31. A method for treating hyperglycemia in a patient in need thereof, comprising administering an effective amount of the compound according to claim 19. 32. A pharmaceutical composition comprising the compound according to claim 20. 33. A pharmaceutical composition comprising the compound according to claim 20 and a pharmaceutically acceptable additive. 34. A method for treating non-insulin-dependent diabetes mellitus (Type 2 diabetes) in a patient in need thereof, comprising administering an effective amount of the compound according to claim 20. 35. A method for treating obesity in a patient in need thereof, comprising administering an effective amount of the compound according to claim 20. 36. A method for treating hyperglycemia in a patient in need thereof, comprising administering an effective amount of the compound according to claim 20. 37. A pharmaceutical composition comprising the compound according to claim 21. 38. A pharmaceutical composition comprising the compound according to claim 21 and a pharmaceutically acceptable additive. 39. A method for treating non-insulin-dependent diabetes mellitus (Type 2 diabetes) in a patient in need thereof, comprising administering an effective amount of the compound according to claim 21. 40. A method for treating obesity in a patient in need thereof, comprising administering an effective amount of the compound according to claim 21. 41. A method for treating hyperglycemia in a patient in need thereof, comprising administering an effective amount of the compound according to claim 21.