Substituted amino six-membered saturated heteroalicycles as long-acting DPP-IV inhibitors

Patent metadata

Field	Value
Publication number	US-10155775-B2
Application number	US-201615549773-A
Country	US
Kind code	B2
Filing date	Feb 4, 2016
Priority date	Feb 12, 2015
Publication date	Dec 18, 2018
Grant date	Dec 18, 2018

Abstract

The present application relates to a substituted amino six-membered saturated heteroalicycle represented by formula I as a long-acting DPP-IV inhibitor, a method for preparing the same, a pharmaceutical composition comprising the same, and a use of the same in treating and/or preventing diseases and disorders benefitting from DPP-IV inhibition.

First claim

What is claimed is:

1. A compound having the following formula (IV):

wherein,
X is O;
Y is selected from the group consisting of N and CH;
R 1 is selected from the group consisting of —NH 2 and —OH;
R 2 and R 3 are both H;
R 4a and R 4b are each independently selected from the group consisting of F, Cl, Br, —NH 2 and —OH;
R 5c and R 5d together with the atoms of pyrazole ring to which they are attached form a 5, 6 or 7-membered non-aromatic ring, and
a pharmaceutically acceptable salt thereof.

2. A compound having the following formula (V):

wherein the substitution position of R 5 is positions of R 5 , and R 5b shown in the structure represented by formula VII or formula VIII:

wherein,
X is O;
Y is selected from the group consisting of N and CH;
R 1 is selected from the group consisting of —NH 2 and —OH;
R 2 and R 3 are both H;
each R 4 is independently selected from the group consisting of F, Cl, Br, NH 2 , and OH;
R 5a is selected from the group consisting of —NHR 7 and —SO 2 R 8 ;
R 5b is selected from the group consisting of F Cl Br and I;
R 7 is —SO 2 R 8 ,
each R 8 is independently selected from the group consisting of —OH, —NH 2 , C 1-6 alkyl and C 3-6 cycloalkyl; and
o is independently 1, 2 or 3, p is 1 or 2, and
a pharmaceutically acceptable salt thereof.

3. The compound of claim 2 , wherein each R 8 is independently selected from the group consisting of —OH, —NH 2 , methyl, ethyl, propyl, butyl, C 3 cycloalkyl, C 4 cycloalkyl and C 5 cycloalkyl.

4. The compound of claim 2 , wherein o is 2.

5. The compound of claim 2 , wherein a substitution position of R 4 is positions of R 4a and R 4b shown in the structure represented by formula VI:

wherein R 4a and R 4b are each independently selected from the group consisting of F, Cl, Br, I, —NH 2 and OH; R 5 is defined the same as R 5a when p is 1; R 5 s are defined the same as R 5a and R 5b , respectively, when p is 2; and the remaining groups are defined the same as in claim 2 .

6. The compound of claim 2 selected from the group consisting of the following:

7. A pharmaceutical composition, comprising the compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutical acceptable carrier.

8. A method for the treatment of diseases and disorders benefitting from DPP-IV inhibition, comprising administering to a subject in need thereof the compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein the diseases and disorders benefitting from DPP-IV inhibition are type II diabetes.

9. A method for the treatment of diseases and disorders benefitting from DPP-IV inhibition, comprising administering to a subject in need thereof the pharmaceutical composition of claim 7 , wherein the diseases and disorders benefitting from DPP-IV inhibition are type II diabetes.

10. The compound of claim 1 , wherein the 5, 6 or 7-membered non-aromatic ring contains 1, 2 or 3 heteroatoms independently selected from the group consisting of N, O and S.

11. The compound of claim 10 , wherein the 5, 6 or 7-membered non-aromatic ring contains an —SO 2 — group.

12. The compound of claim 1 , which has the following structure:

13. A pharmaceutical composition, comprising the compound of claim 1 , or a pharmaceutically acceptable salt and a pharmaceutical acceptable carrier.

14. A method for the treatment of diseases and disorders benefitting from DPP-IV inhibition, comprising administering to a subject in need thereof the compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the diseases and disorders benefitting from DPP-IV inhibition are type II diabetes.

15. A method for the treatment of diseases and disorders benefitting from DPP-IV inhibition, comprising administering to a subject in need thereof the pharmaceutical composition of claim 13 , wherein the diseases and disorders benefitting from DPP-IV inhibition are type II diabetes.

16. A compound having the following structure:

17. A pharmaceutical composition, comprising the compound of claim 16 , or a pharmaceutically acceptable salt and a pharmaceutical acceptable carrier.

18. A method for the treatment of diseases and disorders benefitting from DPP-IV inhibition, comprising administering to a subject in need thereof the compound of claim 16 , or a pharmaceutically acceptable salt thereof, wherein the diseases and disorders benefitting from DPP-IV inhibition are type II diabetes.

19. A method for the treatment of diseases and disorders benefitting from DPP-IV inhibition, comprising administering to a subject in need thereof the pharmaceutical composition of claim 17 , wherein the diseases and disorders benefitting from DPP-IV inhibition are type II diabetes.

Assignees

• Centaurus Biopharma Co Ltd
• Chia Tai Tianqing Pharmaceutical Group Co Ltd
• Lianyungang Runzhong Pharmaceutical Co Ltd
• Chia Tai Tianqing Pharmaceutical Co Ltd

Inventors

• Xu Xinhe
• Shen Yu
• Xiao Dengming
• Luo Hong
• Peng Yong
• Han Yongxin
• Zhang Aiming
• Yang Ling

Classifications

• C07D513/14 Primary

  Ortho-condensed systems · CPC title

• A61K31/4162

  condensed with heterocyclic ring systems · CPC title

• A61K31/4035

  Isoindoles, e.g. phthalimide · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title