EGFR inhibitors
The present disclosure provides a compound represented by structural formula (I): or a pharmaceutically acceptable salt thereof useful for treating a cancer.
1. A compound of Formula (II-A):
or a pharmaceutically acceptable salt thereof, wherein:
Z is O;
R is H, halogen, or CH 3 ;
Ring A is piperidinyl optionally substituted with 1-6 R 1 ;
each R 1 is independently halogen, CN, OH, NR a R b , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 3 -C 6 cycloalkyl or —O-C 3 -C 6 cycloalkyl, wherein the alkyl, alkoxy or cycloalkyl represented by R 1 or in the group represented by R 1 is optionally substituted with 1 to 3 groups selected from deuterium, halogen, OH, NR a R b , C 1 -C 2 alkyl, and C 1 -C 2 alkoxy;
m is 0, 1, 2, 3, 4, 5, or 6;
R 2 is H or isopropyl;
R 4 is H or methyl;
R 5 is H; C 1 -C 4 alkyl optionally substituted with 1 to 3 three groups selected from halogen, CN, and NR a R b ; C 3 -C 6 cycloalkyl; or 4-6 membered monocyclic heterocyclyl optionally substituted with C 1 -C 4 alkyl;
R 6 is H, CH3, or CH2NH2; and
wherein R a and R b are each independently selected from H, methyl and ethyl.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 1, 2, 3, 4, or 5; and
each R 1 is independently halogen, CN, OH, NR a R b , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —O-C 3 -C 6 cycloalkyl, wherein the alkyl, alkoxy, or cycloalkyl represented by R 1 or in the group represented by R 1 is optionally substituted with 1 to 3 groups selected from deuterium, halogen, OH, NR a R b , C 1 -C 2 alkyl, and C 1 -C 2 alkoxy.
3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein at least one R 1 is OH, C 1 -C 4 alkoxy, or —O-C 3 -C 6 cycloalkyl, wherein the alkoxy or cycloalkyl represented by R 1 or in the group represented by R 1 is optionally substituted with 1 to 3 groups selected from deuterium, halogen, OH, NR a R b , C 1 -C 2 alkyl, and C 1 -C 2 alkoxy.
4. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently F, CN, OH, NH 2 , CH 3 , CH 2 CH 3 , CHF 2 , CH(OH)CH 3 , CH 2 OH, CH 2 NH 2 , CH 2 CH 2 NH 2 , OCH 3 , OCD 3 , OCH 2 CH 2 OH, OCH 2 CH(OH)CH 3 , OCH 2 C(OH)(CH 3 ) 2 , OCH 2 CH 2 OCH 3 , OCH 2 CH 2 NH 2 , OCH 2 CH 2 NHCH 3 , OCH 2 CH 2 N(CH 3 ) 2 , —O- cyclopropyl, NHCH 3 , or N(CH 3 ) 2 .
5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein
6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
7. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
8. A compound, wherein the compound is:
or a pharmaceutically acceptable salt thereof.