	US 12,064,433 B2
	Pyridone A2R antagonists
Manmohan Reddy Leleti, Dublin, CA (US); Debashis Mandal, Fremont, CA (US); Dillon Harding Miles, Berkeley, CA (US); Jay Patrick Powers, Pacifica, CA (US); Brandon Reid Rosen, San Mateo, CA (US); and Ehesan U I Sharif, Menlo Park, CA (US)
Assigned to ARCUS BIOSCIENCES, INC., Hayward, CA (US)
Appl. No. 17/263,016
Filed by ARCUS BIOSCIENCES, INC., Hayward, CA (US)
PCT Filed Jul. 26, 2019, PCT No. PCT/US2019/043608 § 371(c)(1), (2) Date Jan. 25, 2021, PCT Pub. No. WO2020/023846, PCT Pub. Date Jan. 30, 2020.
Claims priority of provisional application 62/711,273, filed on Jul. 27, 2018.
Prior Publication US 2021/0161898 A1, Jun. 3, 2021
Int. Cl. A61K 33/243 (2019.01); A61K 31/282 (2006.01); A61K 31/517 (2006.01); A61K 31/519 (2006.01); A61K 31/704 (2006.01); A61K 45/06 (2006.01); C07D 401/14 (2006.01); C07D 405/14 (2006.01)

CPC A61K 31/517 (2013.01) [A61K 31/282 (2013.01); A61K 31/519 (2013.01); A61K 31/704 (2013.01); A61K 33/243 (2019.01); A61K 45/06 (2013.01); C07D 401/14 (2013.01); C07D 405/14 (2013.01)]

25 Claims

1. A compound represented by Formula (I)

or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein,

G¹is N or CR^3a;

G²is N or CR^3b;

R^3aand R^3bare each independently H or C_1-3alkyl;

R^1aand R^1bare each independently selected from the group consisting of

i) H,

ii) C_1-8alkyl optionally substituted with from 1-3 R⁵substituents,

iii) —X¹—O—C_1-8alkyl optionally substituted with from 1-3 R⁵substituents,

iv) —C(O)—R⁶,

v) Y optionally substituted with 1-3 R⁷substituents,

vi) —X¹—Y optionally substituted with 1-3 R⁷substituents; and

vii)R^1aand R^1btogether with the nitrogen to which they are attached form a 5-6 membered heterocycloalkyl ring optionally substituted with from 1-3 R⁸substituents, wherein the heterocycloalkyl has 0-2 additional heteroatom ring vertices selected from the group consisting of O, N, and S;

each Y is C_3-8cycloalkyl or 4 to 6-membered heterocycloalkyl having 1-3 heteroatom ring vertices selected from the group consisting of O, N, and S;

R²and R⁴are each independently H or C_1-3alkyl;

each X¹is C_1-6alkylene;

each R⁵is independently selected from the group consisting of hydroxyl, C_3-8cycloalkyl, phenyl, —O-phenyl, —C(O)OR^a, and oxo;

each R⁶is C_1-8alkyl or Y, each of which is optionally substituted with 1-3 substituents selected from the group consisting of hydroxyl, —O-phenyl, phenyl, and —O—C_1-8alkyl;

each R⁷is independently selected from the group consisting of C_1-8alkyl, hydroxyl, —O—C_1-8alkyl, oxo, and —C(O)OR^a;

each R⁸is independently selected from the group consisting of C_1-8alkyl, hydroxyl, and oxo;

the subscript n is 0, 1, 2 or 3;

each R⁹is independently selected from the group consisting of C_1-8alkyl, —O—C_1-8alkyl, —X¹—O—C_1-8alkyl, —O—X¹—O—C_1-8alkyl, —X¹—O—X¹—O—C_1-8alkyl, —C(O)OR^a, halogen, cyano, —NR^bR^c, Y, —X¹—C_3-8cycloalkyl, and —X²—Z, wherein X²is selected from the group consisting of C_1-6alkylene, —C_1-6alkylene-O—, —C_1-4alkylene-O—C_1-4alkylene-, —C(O)—, and —S(O)₂—, Z is 4 to 6-membered heterocycloalkyl having 1-3 heteroatom ring vertices selected from the group consisting of O, N, and S, and wherein each of said R⁹substituents is optionally substituted with 1-3 R¹¹;

each of R^10a, R^10b, R^10c, and R^10dis independently selected from the group consisting of H, C_1-8alkyl, halo, cyano, —O—C_1-8alkyl, —X¹—O—C_1-8alkyl, —O—X¹—O—C_1-8alkyl, —S(O)₂—C_1-6alkyl, —C(O)NR^dR^c, and 4-6-membered heteroaryl having from 1-3 heteroatom ring vertices selected from the group consisting of O, N, and S, wherein each of said R^10a-dsubstituents is optionally substituted with 1-3 R¹², or two of R^10a, R^10b, R^10cand R^10don adjacent ring vertices are optionally combined to form a 5-membered heterocyclic ring optionally substituted with 1-2 halogens;

each R¹¹is independently selected from the group consisting of hydroxyl, oxo, halo, cyano, —NR^dR^e, —C(O)OR^a, phenyl, C_3-8cycloalkyl, and C_1-4alkyl optionally substituted with —C(O)OR^a;

each R¹²is independently selected from the group consisting of halo, cyano, hydroxy, and —C(O)OR^a;

each R^ais H or C_1-6alkyl;

each R^band R^care independently selected from the group consisting of H, C_1-8alkyl, —S(O)₂—C_1-6alkyl, —C(O)OR^a, and —X¹—C(O)OR^a; and

each R^dand R^eare independently selected from the group consisting of H, C_1-8alkyl, and —S(O)₂—C_1-6alkyl.