US 11,814,379 B2
Cyano quinoline amide compounds as HER2 inhibitors and methods of use
Nathanael S. Gray, Boston, MA (US); Jaebong Jang, Boston, MA (US); Pasi Janne, Needham, MA (US); and Jieun Son, Boston, MA (US)
Assigned to Dana-Farber Cancer Institute, Inc., Boston, MA (US)
Appl. No. 16/973,276
Filed by DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
PCT Filed Jun. 14, 2019, PCT No. PCT/US2019/037327
§ 371(c)(1), (2) Date Dec. 8, 2020,
PCT Pub. No. WO2019/241715, PCT Pub. Date Dec. 19, 2019.
Claims priority of provisional application 62/684,949, filed on Jun. 14, 2018.
Prior Publication US 2021/0355119 A1, Nov. 18, 2021
Int. Cl. C07D 215/54 (2006.01); C07D 401/12 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01); A61P 35/00 (2006.01); C07D 417/12 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 35/00 (2018.01); C07D 215/54 (2013.01); C07D 401/12 (2013.01); C07D 417/12 (2013.01); C07D 487/04 (2013.01)] 19 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or solvate thereof, wherein:
A is

OG Complex Work Unit Chemistry

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and is optionally substituted with one or more RA;
each RA is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, OH, CN, NO2, NH2, C1-C6 alkylamino, or di-C1-C6 alkylamino;
X is C—CN;
R1 is C1-C6 alkyl or (CH2)1-3-heterocyclyl comprising one 5- or 6-membered ring and 1-3 heteroatoms selected N and O and at least one N, wherein the alkyl is optionally substituted with one or more RB′ and the heterocyclyl is optionally substituted with one or more RB;
m is 0, 1, or 2;
each R2 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, OH, CN, NO2, NH2, C1-C6 alkylamino, di-C1-C6 alkylamino, or NHC(O)R5;
n is 0, 1, 2, 3, or 4;
each R3 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, OH, CN, NO2, NH2, C1-C6 alkylamino, or di-C1-C6 alkylamino;
R4 and R5 are each independently C2-C4 alkenyl optionally substituted with one or more Rx;
each Rx is independently NH2, C1-C3 alkylamino, or di-C1-C3 alkylamino;
each RB′ is independently C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, OH, CN, NO2, NH2, C1-C6 alkylamino, or di-C1-C6 alkylamino; and
each RB is independently C1-C6 alkyl, C1-C6 haloalkyl, or RB′,
wherein when A is 4-quinolinyl and n is 1, then R3 is not halogen.