Novel cyclosporin analogues for preventing or treating hepatitis c infection

Patent metadata

Field	Value
Publication number	US-2016136233-A1
Application number	US-201514948876-A
Country	US
Kind code	A1
Filing date	Nov 23, 2015
Priority date	Aug 26, 2013
Publication date	May 19, 2016
Grant date	—

Abstract

The present invention relates to novel cyclosporine analogues having antiviral activity against HCV and useful in the treatment of HCV infections. More particularly, the invention relates to novel cyclosporine analogue compounds, compositions containing such compounds and methods for using the same, as well as processes for making such compounds.

First claim

What is claimed:

1 . A compound represented by the formula:

R 11 is selected from:
a) R 11 , where is selected from:
1) Hydrogen;
2) Deuterium;
3) C 1 -C 8 alkyl;
4) Substituted C 1 -C 8 alkyl;
5) C 2 -C 8 alkenyl;
6) Substituted C 2 -C 8 alkenyl;
7) C 2 -C 8 alkynyl;
8) Substituted C 2 -C 8 alkynyl;
9) C 3 -C 12 cycloalkyl;
10) Substituted C 3 -C 12 cycloalkyl;
11) Aryl;
12) Substituted aryl;
13) Heterocycloalkyl;
14) Substituted heterocycloalkyl;
15) Heteroaryl; or
16) Substituted heteroaryl;

b) —C(O)N(R 12 )(R 13 ), where R 12 and R 13 are independently selected from R 11 and R 11 is as previously defined or R 12 and R 13 combined together with the N which attached to is substituted or unsubstituted heterocycloalkyl;
c) R 14 , where R 14 is selected from:
1) -M-R 11 , where R 11 is as previously defined and M is selected from:
i. C 1 -C 8 alkylene;
ii. Substituted C 1 -C 8 alkylene;
iii. C 2 -C 8 alkenylene;
iv. Substituted C 2 -C 8 alkenylene;
v. C 2 -C 8 alkynylene;
vi. Substituted C 2 -C 8 alkynylene;
vii. C 3 -C 12 cycloalkylene;
viii. Substituted C 3 -C 12 cycloalkylene;

2) -M-NR 15 R 11 , where R 15 is R 11 or R 15 and R 11 combined together with the N which attached to is substituted or unsubstituted heterocycloalkyl, M is as previously defined;
3) -M-S(O) m R 11 , where m=0, 1, or 2; M and R 11 are as previously defined;
4) -M-OR 11 , where M and R 11 are as previously defined;
5) -M-C(O) R 16 , where M is as previously defined and R 16 is selected from:
i. C 1 -C 8 alkyl;
ii. Substituted C 1 -C 8 alkyl;
iii. C 2 -C 8 alkenyl;
iv. Substituted C 2 -C 8 alkenyl;
v. C 2 -C 8 alkynyl;
vi. Substituted C 2 -C 8 alkynyl;
vii. C 3 -C 12 cycloalkyl; and
viii. Substituted C 3 -C 12 cycloalkyl;

6) -M-OC(O) R 16 , where M and R 16 are as previously defined;
7) -M-OC(O)O R 16 , where M and R 16 are as previously defined;
8) -M-NR 17 C(O) R 16 , where R 17 is R 11 , M and R 16 are as previously defined;
9) -MNR 17 C(O)O R 16 , where R 17 , M and R 16 are as previously defined;
10) -M-C(O)NR 17 R 11 , where R 17 , M and R 11 are as previously defined;
11) -M-C(O)N(R 17 )—OR 11 , where R 17 , M and R 11 are as previously defined;
12) -M-OC(O)NR 17 R 11 , where R 17 , M and R 11 are as previously defined;
13) -M-NR 17 C(O)NR 16 R 11 , where M, R 11 , R 17 and R 16 are as previously defined or R 16 and R 11 combined together with the N which attached to is substituted or unsubstituted heterocycloalkyl;
14) -M-C(S)S R 11 , where M and R 11 are as previously defined;
15) -M-OC(S)S R 16 , where M and R 16 are as previously defined;
16) -M-NR 17 C(O)S R 16 , where M, R 17 and R 16 are as previously defined;
17) -M-SC(O)NR 17 R 11 , where M, R 11 and R 17 are as previously defined or R 17 and R 11 combined together with the N which attached to is substituted or unsubstituted heterocycloalkyl;
18) -M-CH═N—O R 11 , where M and R 11 are as previously defined;
19) -M-CH═N—NR 17 R 11 , where M, R 11 and R 17 are as previously defined or R 17 and R 11 combined together with the N which attached to is substituted or unsubstituted heterocycloalkyl;

A is R 1 and R 1 is not

R 2 , R 3 and R 4 are independently selected from: hydrogen or methyl.

2 . A compound according to claim 1 , which is represented by the formula (II):

wherein R 1 , R 3 , R 4 and A are as defined in claim 1 .

3 . A compound according to claim 1 , which is represented by the formula (III):

wherein R 1 and A are as defined in claim 1 .

4 . A compound according to claim 1 , as set forth in Table 1 which is selected from compounds of Formula IV;
compounds in Table 1 are represented by Formula (IV), wherein A is delineated for each example of Table 1:

TABLE 1

Compound
A

 1

 2

 3

 4

 5

 6

 7

 8

 9

10

11

Assignees

• Enanta Pharm Inc

Inventors

• Or Yat Sun
• Wang Guoqiang
• Long Jiang
• Kim In Jong

Classifications

• A61P31/20

  for DNA viruses · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P31/18

  for HIV · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title