N-hydroxyamide derivatives and use thereof
The present invention is related to N-hydroxyamide derivatives of Formula (I) and use thereof in particular for the treatment and/or prophylaxis of autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, cancer, respiratory diseases and fibrosis, including multiple sclerosis, arthritis, emphysema, chronic obstructive pulmonary disease, liver and pulmonary fibrosis.
1. An N-hydroxyamide derivative of Formula (I),
wherein:
A is C(B);
B is H or B forms a bond with either R 5 or R 7 ;
R 1 is selected from H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 -cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 3 -C 8 -cycloalkyl C 1 -C 6 alkyl, heterocycloalkyl C 1 -C 6 alkyl, heteroaryl C 1 -C 6 alkyl, amino or alkoxy;
R 2 is selected from H, substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 4 : cycloalkyl, C 6 -C 8 -cycloalkyl, heterocycloalkyl, alkoxy, aryl or heteroaryl;
R 3 is selected from H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl;
R 4 , R 5 , R 6 and R 7 are independently selected from H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl; or R 4 and R 7 form together a —CH 2 — linkage; and
n is an integer selected from 1, 2, 3, 4, 5 and 6;
or pharmaceutically acceptable salts thereof,
wherein carbons (2) and (3) are two chiral centers, chiral center (2) has a configuration selected from “S” and “R” and chiral center (3) has an “S”.
2. The N-hydroxyamide derivative according to claim 1 having a Formula (Ia):
wherein A is CH;
R 1 is selected from H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 -cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 3 -C 8 -cycloalkyl C 1 -C 6 alkyl, heterocycloalkyl C 1 -C 6 alkyl, heteroaryl C 1 -C 6 alkyl, amino or alkoxy;
R 2 is selected from H, substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 4 -cycloalkyl, C 6 -C 8 -cycloalkyl, heterocycloalkyl, alkoxy, aryl or heteroaryl;
R 3 is selected from H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl;
R 4 , R 5 , R 6 and R 7 are independently selected from H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl; or R 4 and R 7 form together a —CH 2 — linkage; and
n is an integer selected from 1, 2, 3, 4, 5 and 6;
or pharmaceutically acceptable salts thereof,
wherein carbons (2) and (3) are two chiral centers, chiral center (2) has a configuration selected from “S” and “R” and chiral center (3) has an “S” configuration.
3. The N-hydroxyamide derivative according to claim 1 , wherein R 1 is selected from aryl and heteroaryl.
4. The N-hydroxyamide derivative according to claim 1 ,
wherein R 2 is selected from H, substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl and C 2 -C 6 alkynyl.
5. The N-hydroxyamide derivative according to claim 1 , wherein R 3 is H.
6. The N-hydroxyamide derivative according to claim 1 , wherein R 4 , R 5 and R 7 are H.
7. The N-hydroxyamide derivative according to claim 2 , wherein R 1 is selected from aryl and heteroaryl.
8. The N-hydroxyamide derivative according to claim 2 , wherein R 2 is selected from H, substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl and C 2 -C 6 alkynyl.
9. The N-hydroxyamide derivative according to claim 2 , wherein R 3 is H.
10. The N-hydroxyamide derivative according to claim 2 , wherein R 4 , R 5 and R 7 are H.
11. A pharmaceutical composition comprising at least one N-hydroxyamide derivative according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.