US 11,697,650 B2
Compounds having tetrahydroindolizine-1-carboxamide as BCL-2 inhibitors
Volodymyr Kysil, San Diego, CA (US); Vladislav Zenonovich Parchinsky, Moscow (RU); Alexei Pushechnikov, San Diego, CA (US); Alexandre Vasilievich Ivachtchenko, Hallandale Beach, FL (US); Ruben Abagyan, La Jolla, CA (US); Andrew Orry, San Diego, CA (US); Polo Chun-Hung Lam, San Diego, CA (US); and Nikolay Savchuk, San Diego, CA (US)
Assigned to Eil Therapeutics, Inc., San Diego, CA (US)
Filed by Eil Therapeutics, Inc., San Diego, CA (US)
Filed on Mar. 11, 2022, as Appl. No. 17/692,923.
Claims priority of provisional application 63/160,208, filed on Mar. 12, 2021.
Prior Publication US 2022/0289745 A1, Sep. 15, 2022
Int. Cl. C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) 61 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof,
wherein:
Ring A is selected from aryl or heteroaryl;
each R1 is independently selected from halo, —OH, —CN, —NO2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, aryl, —C(O)OR4, and —C(O)NR5R6, wherein aryl is optionally substituted with one or more R7;
R2 is selected from H, C1-C6 alkyl, and —C(O)R4;
R3 is selected from 3- to 8-membered heterocyclyl, —O(CH2O)oR8, and —N(R9)2, wherein the heterocyclyl is optionally substituted with one or more R10;
each R4 is independently selected from H and C1-C6 alkyl;
each R5 is independently selected from H, C1-C6 alkyl, —(CH2)pOR11, —(CH2)pN(R11)2, and S(O)2R11;
each R6 is independently selected from H and C1-C6 alkyl,
or R5 and R6, together with the atom to which they are attached, come together to form a 3- to 10-membered heterocyclyl ring further comprising 1, 2, or 3 heteroatoms selected from N, O, and S, wherein the heterocyclyl is optionally substituted with one or more R11;
each R7 is independently selected from halo, —OH, —CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy;
R8 is selected from H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, and 3- to 8-membered heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more R10;
each R9 is independently selected from H, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
each R10 is independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, and —OH;
each R11 is independently selected from H and C1-C6 alkyl;
m is an integer selected from 0, 1, 2, 3, 4, and 5; and
n is an integer selected from 0, 1, 2, 3, and 4;
o is an integer selected from 0, 1, and 2; and
p is an integer selected from 0, 1, 2, 3, 4, 5, and 6.