Substituted 2-morpholinopyridine derivatives as ATR kinase inhibitors
Disclosed are compounds and pharmaceutically acceptable salts thereof that may be used in the treatment of subjects in need thereof. The compounds disclosed herein may be inhibitors of Ataxia-telangiectasia and RAD-3-related protein kinase (ATR). Also disclosed are pharmaceutical compositions containing the compounds or pharmaceutically acceptable salts thereof and methods of their preparation and use.
1 . A compound of formula (I):
or a pharmaceutically acceptable salt thereof,
wherein
is a double bond, and each Y is independently N or CR 4 ; or is a single bond, and each Y is independently NR Y , carbonyl, or C(R Y ) 2 ; wherein each R Y is independently H or optionally substituted C 1-6 alkyl;
R 1 is methyl;
R 3 is optionally substituted C 1-9 heteroaryl or optionally substituted C 1-9 heteroaryl C 1-6 alkyl;
each R 4 is independently hydrogen, halogen, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, or optionally substituted C 2-6 alkynyl; and
X is hydrogen or halogen.
2 . The compound of claim 1 , wherein the compound is a compound of formula (II):
or a pharmaceutically acceptable salt thereof.
3 . The compound of claim 1 , wherein the compound is a compound of formula (IB):
or a pharmaceutically acceptable salt thereof.
4 . The compound of claim 1 , wherein the compound is a compound of formula (IB-a):
or a pharmaceutically acceptable salt thereof.
5 . The compound of claim 1 , wherein R 3 is optionally substituted, monocyclic C 1-9 heteroaryl comprising at least one nitrogen atom.
6 . The compound of claim 1 , wherein R 3 is:
7 . The compound of claim 1 , wherein R 4 is hydrogen.
8 . The compound of claim 1 , wherein X is hydrogen.
9 . A compound selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
10 . The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
11 . The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
12 . The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
13 . The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
14 . The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
15 . A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.