US 11,807,649 B2
Fused tetracyclic quinazoline derivatives as inhibitors of ErbB2
Joseph P. Lyssikatos, Boulder, CO (US); Samuel Kintz, Boulder, CO (US); Li Ren, Superior, CO (US); and Qiang Su, Beijing (CN)
Assigned to EnLiven Therapeutics, Inc., Boulder, CO (US)
Filed by EnLiven Therapeutics, Inc., Boulder, CO (US)
Filed on Nov. 1, 2022, as Appl. No. 18/051,826.
Claims priority of provisional application 63/417,219, filed on Oct. 18, 2022.
Claims priority of application No. PCT/CN2021/128110 (WO), filed on Nov. 2, 2021.
Prior Publication US 2023/0159557 A1, May 25, 2023
Int. Cl. C07D 498/18 (2006.01); C07D 519/00 (2006.01); A61P 35/02 (2006.01)
CPC C07D 498/18 (2013.01) [A61P 35/02 (2018.01); C07D 519/00 (2013.01); C07B 2200/05 (2013.01)] 44 Claims
 
1. A compound of formula (I′)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, solvate, hydrate, or co-crystal thereof, or a mixture of any of the foregoing, wherein Ring A is

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
E is —C(═O)—R1;
G is —O—, —C(═O)—, —S—, —S(O)—, —S(O)2—, or —CH2—;
V is O, S, or N—R2;
each X1 is independently N or CH;
X2 is O, S, or N—R3;
Y is N or C—Ry, wherein Ry is —H or —F;
Z is —H, halogen, —C≡CH, —OCH3, or C1-C2 alkyl;
R1 is C2-C4 alkenyl or C2-C4 alkynyl, each of which is independently optionally substituted by 1-4 substituents selected from the group consisting of halogen, C1-C3 alkyl, a 3- to 7-membered carbon-linked N-heterocycloalkyl, or —NR1aR1b, wherein each R1a and R1b are independently —H, C1-C3 alkyl, or —CD3, or wherein each pair of geminal R1a and R1b may be taken together with the nitrogen atom to which they are attached to form a 3- to 6-membered N-heterocyclyl, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3 alkyl;
R2 is C1-C6 alkyl or C1-C6 cycloalkyl, each of which is independently optionally substituted by 1-4 fluorines;
R3 is —H, C1-C6 alkyl, —CD3 or C1-C6 cycloalkyl;
R4 is —H or halogen;
R5 is —H or halogen;
R6 is —H or halogen;
R7 is —H, halogen, C1-C6 alkyl, —CD3 or C1-C6 cycloalkyl;
n is 1 or 2;
p is 0 or 1; and
q is 1 or 2.