Z is —NH—;

R⁷is alkyl, cycloalkyl, or 1,1′-bi(cyclopropan)-1-yl;

wherein the alkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and

wherein the cycloalkyl or 1,1′-bi(cyclopropan)-1-yl is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

X is O;

Y is CH, CF, or N;

A is H, halo, CN, C1-C6 alkyl, alkyl(carbocyclyl), alkyl(heterocyclyl), C2-C6 alkenyl, C2-C6 alkynyl, alkynyl(carbocyclyl), NR⁹R⁹, OH, OC1-C6 alkyl, C3-C7 carbocyclyl, heterocyclyl, aryl, or heteroaryl;

wherein the C1-C6 alkyl, alkyl portion of alkyl(carbocyclyl), alkyl portion of alkyl(heterocyclyl), C2-C6 alkenyl, C2-C6 alkynyl, alkynyl portion of alkynyl(carbocyclyl), or OC1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and

wherein the carbocyclyl portion of alkyl(carbocyclyl), heterocyclyl portion of alkyl(heterocyclyl), carbocyclyl portion of alkynyl(carbocyclyl), C3-C7 carbocyclyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of halo, CN, NO₂, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

each R⁹is independently H or C1-C6 alkyl, wherein each C1-C6 alkyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

G is a bond, cycloalkylene, or heterocycloalkylene, wherein the cycloalkylene or heterocycloalkylene is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

R¹is alkyl, alkyl(cycloalkyl), alkyl(heterocyclyl), aralkyl, alkyl(heteroaryl), alkenyl, or alkynyl;

wherein the alkyl, alkyl portion of alkyl(cycloalkyl), alkyl portion of alkyl(heterocyclyl), alkyl portion of aralkyl, alkyl portion of alkyl(heteroaryl), alkenyl, or alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and

wherein the cycloalkyl portion of alkyl(cycloalkyl), heterocyclyl portion of alkyl(heterocyclyl), aryl portion of aralkyl, or heteroaryl portion of alkyl(heteroaryl) is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

R²is H, halo, CN, alkyl, alkyl(cycloalkyl), alkyl(heterocyclyl), alkenyl, alkynyl, alkynyl(cycloalkyl), OH, cycloalkyl, heterocyclyl, aryl, or heteroaryl;

wherein the alkyl, alkyl portion of alkyl(cycloalkyl), alkyl portion of alkyl(heterocyclyl), alkenyl, alkynyl, or alkynyl portion of alkynyl(cycloalkyl) is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and

wherein the cycloalkyl portion of alkyl(cycloalkyl), heterocyclyl portion of alkyl(heterocyclyl), cycloalkyl portion of alkynyl(cycloalkyl), cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

R³is H, halo, CN, alkyl, alkyl(cycloalkyl), alkyl(heterocyclyl), alkenyl, alkynyl, alkynyl(cycloalkyl), OH, cycloalkyl, heterocyclyl, aryl, or heteroaryl;

wherein the alkyl, alkyl portion of alkyl(cycloalkyl), alkyl portion of alkyl(heterocyclyl), alkenyl, alkynyl, or alkynyl portion of alkynyl(cycloalkyl) is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and

wherein the cycloalkyl portion of alkyl(cycloalkyl), heterocyclyl portion of alkyl(heterocyclyl), cycloalkyl portion of alkynyl(cycloalkyl), cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; or

R²and R³, taken together with the carbon atom to which they are attached, form a carbocyclyl or heterocyclyl, wherein the carbocyclyl or heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

R⁴is H, halo, CN, alkyl, alkyl(cycloalkyl), alkyl(heterocyclyl), alkenyl, alkynyl, alkynyl(cycloalkyl), OH, cycloalkyl, heterocyclyl, aryl, or heteroaryl;

wherein the alkyl, alkyl portion of alkyl(cycloalkyl), alkyl portion of alkyl(heterocyclyl), alkenyl, alkynyl, or alkynyl portion of alkynyl(cycloalkyl) is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and

wherein the cycloalkyl portion of alkyl(cycloalkyl), heterocyclyl portion of alkyl(heterocyclyl), cycloalkyl portion of alkynyl(cycloalkyl), cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

R⁵is H, halo, CN, alkyl, alkyl(cycloalkyl), alkyl(heterocyclyl), alkenyl, alkynyl, alkynyl(cycloalkyl), OH, cycloalkyl, heterocyclyl, aryl, or heteroaryl;

wherein the alkyl, alkyl portion of alkyl(cycloalkyl), alkyl portion of alkyl(heterocyclyl), alkenyl, alkynyl, or alkynyl portion of alkynyl(cycloalkyl) is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and

wherein the cycloalkyl portion of alkyl(cycloalkyl), heterocyclyl portion of alkyl(heterocyclyl), cycloalkyl portion of alkynyl(cycloalkyl), cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; or

any R⁴and R⁵, taken together with the carbon atom to which they are attached, independently forms a carbocyclyl or heterocyclyl, wherein each carbocyclyl or heterocyclyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; or

R³and R⁴, taken together with the carbon atoms to which they are attached, form a carbocyclyl or heterocyclyl, wherein the carbocyclyl or heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halo, CN, NO₂, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, C(O)R^a, C(O)N(R^a)₂, C(O)OR^a, N(R^a)₂, NR^aC(O)R^a, NR^aC(O)OR^a, NR^aS(O)_tR^a, OR^a, OC(O)R^a, OC(O)N(R^a)₂, OC(O)OR^a, OR^cC(O)N(R^a)₂, ═O, S(O)_tR^a, S(O)_tN(R^a)₂, S(O)_tOR^a, ═S, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

each R^ais independently H, D, alkyl, alkyl(cycloalkyl), alkyl(heterocycloalkyl), aralkyl, alkyl(heteroaryl), cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

each R^cis independently alkylene or alkenylene;

n is 1, 2, or 3; and

each t is independently 1 or 2.

	US 11,939,335 B2
	Substituted imidazo[1,2-a]quinazolines and imidazo [1,2-a]pyrido[4,3-e]pyrimidines as inhibitors of PARG
James M. Veal, Solana Beach, CA (US); Jeffrey A. Stafford, Rancho Santa Fe, CA (US); Donald S. Karanewsky, Escondido, CA (US); and Shyama Herath, San Diego, CA (US)
Assigned to 858 THERAPEUTICS, INC., San Diego, CA (US)
Filed by 858 Therapeutics, Inc., San Diego, CA (US)
Filed on May 19, 2023, as Appl. No. 18/199,900.
Application 18/199,900 is a continuation of application No. PCT/US2023/022390, filed on May 16, 2023.
Claims priority of provisional application 63/343,005, filed on May 17, 2022.
Prior Publication US 2023/0374022 A1, Nov. 23, 2023
Int. Cl. A61K 31/519 (2006.01); C07D 487/04 (2006.01); C07D 487/14 (2006.01); C07D 491/147 (2006.01); C07D 491/20 (2006.01); C07D 519/00 (2006.01)