Immunomodulators
The present disclosure provides compounds which are immunomodulators and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.
1. A compound of formula (I)
or a pharmaceutically acceptable salt thereof, wherein:
A is
wherein:
denotes the point of attachment to the carbonyl group and denotes the point of attachment to the nitrogen atom;
m is 1;
w is 0, 1, or 2;
R 14 and R 15 are hydrogen;
R 16a is hydrogen;
R 16 is selected from
—CH 2 C(O)NHCH(R 17 )C(O)NH 2 ;
—CH 2 C(O)NHCH(R 17 )C(O)NHCH(R 17a )C(O)NH 2 ; and
—CH 2 C(O)NHCH(R 17 )CO 2 H;
wherein:
X is selected from
—(CH 2 ) 2 CH(CO 2 H)NHC(O)(CH 2 ) p ;
—(CH 2 CH 2 O) q ; and
—(CH 2 CH 2 O) q CH 2 CH 2 NHC(O)CH 2 CH 2 CH(CO 2 H)NHC(O)(CH 2 ) p ;
wherein q is 3, 4, 5, 6, 7, 8, 9, 10, or 11; and
wherein p is 14, 15, or 16;
each R 17a is independently selected from hydrogen and —CH 2 CO 2 H,
each R 17 is —(CH 2 ) z -triazolyl-X—R 35 , wherein z is 1 and R 35 is selected from —CO 2 H and CH 3 ,
R c , R f , R h , R i , R m , and R n are hydrogen;
R a , R e , and R j , are hydrogen;
R b , R k , and R l are methyl;
R 1 is phenylC 1 -C 3 alkyl wherein the phenyl part is optionally substituted with hydroxy, halo, or methoxy;
R 2 is C 1 -C 7 alkyl;
R 3 is amidoC 1 -C 3 alkyl or carboxyC 1 -C 3 alkyl;
R 4 and R d , together with the atoms to which they are attached, form a pyrrolidine ring;
R 5 is selected from imidazolylC 1 -C 3 alkyl, aminoC 1 -C 3 alkyl, and aminobutyl;
R 6 is selected from amidoC 1 -C 3 alkyl, aminoC 1 -C 3 alkyl, aminobutyl, and C 1 -C 7 alkyl;
R 7 and R g , together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted with hydroxy;
R 8 and R 10 are indolylC 1 -C 3 alkyl optionally substituted with carboxyC 1 -C 3 alkyl;
R 9 is hydroxyC 1 -C 3 alkyl or aminoC 1 -C 3 alkyl;
R 11 is C 1 -C 7 alkyl;
R 12 is C 1 -C 7 alkyl; and
R 13 is selected from C 1 -C 7 alkyl, carboxyC 1 -C 3 alkyl, and —(CH 2 ) 3 NHC(NH)NH 2 .
2. A compound which is
or a pharmaceutically acceptable salt thereof.
3. A compound which is
or a pharmaceutically acceptable salt thereof.
4. A compound which is
or a pharmaceutically acceptable salt thereof.
5. A compound which is
or a pharmaceutical acceptable salt thereof.
6. A compound which is
or a pharmaceutically acceptable salt thereof.
7. A compound which is
or a pharmaceutically acceptable salt thereof.
8. A compound which is
or a pharmaceutically acceptable salt thereof.
9. A compound which is
or a pharmaceutically acceptable salt thereof.
10. A compound which is
or a pharmaceutically acceptable salt thereof.
11. A compound which is
or a pharmaceutically acceptable salt thereof.
12. A compound which is
or a pharmaceutically acceptable salt thereof.
13. A compound which is
or a pharmaceutically acceptable salt thereof.
14. A compound which is
or a pharmaceutically acceptable salt thereof.
15. A compound which is
or a pharmaceutically acceptable salt thereof.
16. A compound which is
or a pharmaceutically acceptable salt thereof.
17. A compound which is
or a pharmaceutically acceptable salt thereof.
18. A compound which is
or a pharmaceutically acceptable salt thereof.
19. A compound which is
or a pharmaceutically acceptable salt thereof.
20. A compound which is
or a pharmaceutically acceptable salt thereof.
21. A compound which is
or a pharmaceutically acceptable salt thereof.
22. A compound which is
or a pharmaceutically acceptable salt thereof.
23. A compound which is
or a pharmaceutically acceptable salt thereof.
24. A compound which is
or a pharmaceutically acceptable salt thereof.
25. A compound which is
or a pharmaceutically acceptable salt thereof.
26. A compound which is
or a pharmaceutically acceptable salt thereof.
27. A compound which is
or a pharmaceutically acceptable salt thereof.
28. A compound which is
or a pharmaceutically acceptable salt thereof.
29. A compound which is
or a pharmaceutically acceptable salt thereof.
30. A compound which is
or a pharmaceutically acceptable salt thereof.
31. A compound which is
or a pharmaceutically acceptable salt thereof.
32. A compound which is
or a pharmaceutically acceptable salt thereof.