Compounds and their uses as CD38 inhibitors
The present invention provides compounds of Formula I which can be used as CD38 inhibitors; methods for the production of the compounds of the invention; pharmaceutical compositions comprising the compounds of the invention; as well as uses and methods for treating a disease mediated by CD38 by administering the compounds of the invention.
1 . A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
A 1 is
wherein A 1 is optionally substituted with 0, 1 or 2 substituents independently selected from methyl and trifluoromethyl;
A 2 is
wherein A 2 is optionally substituted with 0 or 1 substituent selected from —CN, methyl, isopropyl, trifluoromethyl, methoxy, cyclobutoxy, oxetan-3-yloxy, —NH 2 , —NHCH 3 , and —N(CH 3 ) 2 ;
A 3 is
wherein A 3 is optionally substituted with 0, 1 or 2 substituents independently selected from —CN, —OCH 2 CH 2 OCH 3 , —COCH 3 , —F, —Cl, methyl, trifluoromethyl, hydroxyethoxy, carboxymethoxy, hydroxy, and methoxy; and
R is H or C 1-6 alkyl.
2 . The compound of claim 1 , wherein A 1 is unsubstituted.
3 . The compound of claim 1 , wherein A 2 is substituted with trifluoromethyl.
4 . The compound of claim 1 , wherein A 3 is
5 . The compound of claim 1 , wherein A 3 is
6 . The compound of claim 1 , wherein R is H.
7 . The compound of claim 1 , wherein R is C 1-6 alkyl.
8 . The compound of claim 2 , wherein A 2 is substituted with trifluoromethyl.
9 . The compound of claim 8 , wherein R is H.
10 . The compound of claim 8 , wherein R is methyl.
11 . The compound of claim 9 , wherein A 3 is
12 . The compound of claim 11 , wherein A 3 is substituted with a substituent selected from —CN, —OCH 2 CH 2 OCH 3 , —COCH 3 , —F, —Cl, methyl, trifluoromethyl, hydroxyethoxy, carboxymethoxy, hydroxy, and methoxy.
13 . The compound of claim 9 , wherein A 3 is
14 . The compound of claim 13 , wherein A 3 is unsubstituted with a substituent selected from —CN, —OCH 2 CH 2 OCH 3 , —COCH 3 , —F, —Cl, methyl, trifluoromethyl, hydroxyethoxy, carboxymethoxy, hydroxy, and methoxy.
15 . The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
16 . The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
17 . The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
18 . The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
19 . The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
20 . The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
21 . A pharmaceutical composition comprising:
a compound of claim 1 or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable or excipient.
22 . The pharmaceutical composition of claim 21 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
23 . The pharmaceutical composition of claim 21 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
24 . The pharmaceutical composition of claim 21 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
25 . The pharmaceutical composition of claim 21 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
26 . The pharmaceutical composition of claim 21 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
27 . The pharmaceutical composition of claim 21 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
28 . A method of inhibiting CD38 function in a cell, comprising contacting a compound of claim 1 or a pharmaceutically acceptable salt thereof with the cell.