N-linked heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders

• US 8,183,381 B2
• Filed: 07/10/2008
• Issued: 05/22/2012
• Est. Priority Date: 07/19/2007
• Status: Expired due to Fees

• Current Assignee: CymaBay Therapeutics Inc.
• Original Assignee: Metabolix Incorporated
• Inventors: Ma, Jingyuan, Rabbat, Christopher J., Song, Jiangao, Chen, Xin, Nashashibi, Imad, Zhao, Zuchun, Novack, Aaron, Shi, Dong Fang, Zhu, Yan, Murphy, Alison, Cheng, Peng
• Primary Examiner(s): Weddington, Kevin E
• Application Number:
  US12/171,209
• Publication Number:
  US 20090137590A1
• Time in Patent Office: 1,412 Days
• Field of Search: 546/275.4
• US Class Current: 546/275.4
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

Compounds and methods are provided for the treatment of, inter alia, Type II diabetes and other diseases associated with poor glycemic control.

Claims

1. A compound of Formula (I):

2. The compound of claim 1, wherein the ring having X, Y and Z is selected from the group consisting of

3. The compound of claim 2, wherein the ring having X, Y and Z is selected from the group consisting of

4. The compound of claim 1, wherein each R⁶ is independently selected from the group consisting of H, halo, —

NR^aR^b, —

NR^aC(O)R^b, —

S(O)R^a, —

S(O)₂R^a, C_1-3alkyl, C_1-3haloalkyl, substituted heteroaryl and unsubstituted heteroaryl.

5. The compound of claim 4 wherein each R⁶ is independently selected from the group consisting of H, fluoro, chloro, methyl, ethyl, —

CF₃, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, —

S(O)R^a, and —

S(O)₂R^a.

6. The compound of claim 1, wherein Ar is a six-membered aryl optionally substituted with from 1 to 3 R⁶ substituents or a heteroaryl, optionally substituted with from 1 to 3 R⁶ substituents.

7. The compound of claim 6, wherein Ar is selected from the group consisting of optionally substituted six-membered aryl, optionally substituted pyridyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, and optionally substituted pyridazinyl.

8. The compound of claim 1, wherein the subscript n is 2.

9. The compound of claim 1, wherein R¹ is selected from the group consisting of —

X¹—

C(O)R^a, —

X¹—

C(O)OR^a, optionally substituted aryl group and optionally substituted heteroaryl group.

10. The compound of claim 9, wherein R¹ is —

C(O)OR^a, pyrimidine optionally substituted with from one to two substituents independently selected from the group consisting of halo, C_3-6cycloalkyl, C_1-10alkyl, and C_1-10substituted alkyl, or oxadiazole.