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US 12,698,261 B2Granted
Cyano-pyrimidine inhibitors of EGFR/HER2
AssigneeDana-Farber Cancer Institute, Inc.
InventorsNathanael S. Gray, John M. Hatcher
Life of this patent
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Abstract
This disclosure provides compounds of Formula (I): or a pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising compounds of Formula (I) or a pharmaceutically acceptable salt thereof which are inhibitors of EGFR and HER2 useful for the treatment of EGFR/HER2 susceptible disorders such as cancer, including cancer of the lung, colon, breast, and thyroid.
Claims19
A compound of Formula I:
- or a pharmaceutically acceptable salt thereof,
- wherein:
- is an optional double bond;
- A, B, and C are, independently at each occurrence, N, C, C—CN, or CH;
- X is N or CH;
- Y is N or O, provided that when Y is O, R6 is absent;
- R1 is selected from the group consisting of hydrogen, halo, hydroxy, cyano, C1-C3 alkyl, C3-C6 cycloalkyl, COR11, CO2R11, and C1-C4 alkoxy, wherein R1 is absent if B is N, C—CN, or CH, and C1-C3 alkyl is optionally substituted with halo;
- R2 is selected from the group consisting of 5-7 membered heteroaryl and C3-C8 cycloalkyl;
- wherein 5-7 membered heteroaryl and C3-C8 cycloalkyl are optionally substituted with one, two, or three R9;
- or R2 is phenyl substituted one, two, or three times with a substituent selected from the group consisting of C1-C6 alkyl, hydroxy, 5-10 membered heteroaryl, O-(5-10 membered heteroaryl), and C1-C6 alkylamine, wherein C1-C6 alkyl is optionally substituted with N(CH3)2;
- R3 is hydrogen or C1-C6 alkyl;
- R4 is hydrogen or C1-C4 alkyl;
- R5 is hydrogen or methyl;
- or
- alternatively, R2 and R5, together with the nitrogen atom to which they are attached, form a 4-7 membered heterocyclic ring;
- R6 is hydrogen or C1-C6 alkyl;
- R7 is C1-C6 alkyl or —C1-C4 alkyl-N(C1-C4 alkyl)2;
- or, alternatively, R6 and R7, together with the nitrogen to which they are attached, form a 4- or 5-membered heterocyclic ring;
- wherein the 4- or 5-membered heterocyclic ring is optionally substituted with one or two R10;
- R8 is hydrogen or —CH2N(CH3)2;
- R9 is, independently at each occurrence, selected from the group consisting of halo, C1-C6 alkyl, hydroxy, C1-C6 alkoxy, 5-10 membered heteroaryl, O-(5-10 membered heteroaryl), and C1-C6 alkylamine, wherein C1-C6 alkyl is optionally substituted with one, two, or three halo or N(CH3);
- or, alternatively, two R9 groups, together with the atoms to which they are attached, form a 3-, 4-, or 5-membered ring;
- R10 is selected from the group consisting of OH, C1-C4 alkoxy, and N(CH3)2;
- and
- R11 is independently, at each occurrence, selected from the group consisting of hydrogen, C1-C6 alkyl, and C3-C6 cycloalkyl.
22 more elements
Dependencies are inferred from the claim text.