1,2,4-oxadiazole compounds as inhibitors of CD47 signalling
The present invention relates to compounds of formula (I), compositions, methods and uses involving the said formula (I) that inhibit CD47 signaling pathway. The present invention also relates to methods of making such compounds and their uses for the treatment of diseases or disorders mediated by CD47.
1. A compound of formula (IA):
or a pharmaceutically acceptable salt or an amide or an ester, or a stereoisomer thereof; wherein,
R a is hydrogen or acyl;
R 1 represents hydrogen, —(CH 2 ) 2 CONH 2 , —(CH 2 ) 2 COOH, —CH 2 COOH, —(CH 2 ) 3 NHC(═NH)NH 2 , —(CH 2 ) 4 NH 2 , —CH 2 CONH 2 , —CH(CH 3 )—CH 2 —CH 3 , —CH 2 -aryl, or —CH 2 — heteroaryl; wherein the said aryl and heteroaryl are unsubstituted; or R a and R 1 , together with the atoms to which they are attached form pyrrolidine ring optionally substituted with oxo group; and
R 2 represents —(CH 2 ) 3 NHC(═NH)NH 2 .
2. The compound of claim 1 , wherein R 1 represents hydrogen, —CH 2 —COOH, —CH 2 —CONH 2 , —CH(CH 3 )—CH 2 —CH 3 , —(CH 2 ) 2 CONH 2 , —(CH 2 ) 2 COOH, —(CH 2 ) 3 NHC(═NH)NH 2 , —(CH 2 ) 4 NH 2 , —CH 2 -phenyl, —CH 2 -indolyl or —CH 2 -imidazolyl.
3. The compound of claim 1 , wherein,
R a is hydrogen; and R 1 represents hydrogen, —CH 2 —COOH, —CH 2 —CONH 2 , —CH(CH 3 )—CH 2 —CH 3 , —(CH 2 ) 2 CONH 2 , —(CH 2 ) 2 COOH, —(CH 2 ) 3 NHC(═NH)NH 2 , —(CH 2 ) 4 NH 2 , —CH 2 -phenyl, —CH 2 -indolyl or —CH 2 -imidazolyl.
4. A compound that is:
Com-
pound
Structure
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
or a pharmaceutically acceptable salt or an amide or an ester, or a stereoisomer thereof.
5. A pharmaceutical composition comprising a compound of formula (IA) according to claim 1 , and a pharmaceutically acceptable carrier.
6. A compound of the formula:
or a pharmaceutically acceptable salt or an amide or an ester, or a stereoisomer thereof.
7. A pharmaceutical composition comprising a compound according to claim 6 , and a pharmaceutically acceptable carrier.
8. The compound of claim 6 , which is of the formula:
9. The compound of claim 6 , which is of the formula:
or a pharmaceutically acceptable salt thereof.
10. The compound of claim 6 , which is of the formula:
or an amide thereof.
11. The compound of claim 6 , which is of the formula:
or an ester thereof.
12. The compound of claim 6 , which is of the formula:
or a stereoisomer thereof.
13. A pharmaceutical composition comprising a compound according to claim 8 , and a pharmaceutically acceptable carrier.
14. A pharmaceutical composition comprising a compound according to claim 9 , and a pharmaceutically acceptable carrier.
15. A pharmaceutical composition comprising a compound according to claim 10 , and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition comprising a compound according to claim 11 , and a pharmaceutically acceptable carrier.
17. A pharmaceutical composition comprising a compound according to claim 12 , and a pharmaceutically acceptable carrier.