US 11,873,291 B2
Quinoline cGAS antagonist compounds
Jian Qiu, Dallas, TX (US); Qi Wei, Dallas, TX (US); Matt Tschantz, Plano, TX (US); Heping Shi, Coppell, TX (US); Youtong Wu, Dallas, TX (US); Hulling Tan, Dallas, TX (US); Lijun Sun, Dallas, TX (US); Chuo Chen, Dallas, TX (US); and Zhijian Chen, Dallas, TX (US)
Assigned to IMMUNESENSOR THERAPEUTICS, INC., Dallas, TX (US); and THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM, Austin, TX (US)
Filed by ImmuneSensor Therapeutics, Inc., Dallas, TX (US); and The Board of Regents of the University of Texas System, Austin, TX (US)
Filed on Sep. 3, 2021, as Appl. No. 17/446,951.
Claims priority of provisional application 63/196,146, filed on Jun. 2, 2021.
Claims priority of provisional application 63/124,713, filed on Dec. 11, 2020.
Claims priority of provisional application 63/074,446, filed on Sep. 3, 2020.
Prior Publication US 2023/0081291 A1, Mar. 16, 2023
Int. Cl. C07D 215/38 (2006.01); C07D 401/14 (2006.01); C07D 215/42 (2006.01); C07D 215/46 (2006.01); C07D 401/04 (2006.01); C07D 403/04 (2006.01); C07D 405/14 (2006.01); C07D 409/14 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 471/08 (2006.01); C07D 491/048 (2006.01); C07F 9/6503 (2006.01); C07F 9/6506 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 215/38 (2013.01); C07D 215/42 (2013.01); C07D 215/46 (2013.01); C07D 401/04 (2013.01); C07D 403/04 (2013.01); C07D 405/14 (2013.01); C07D 409/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 471/08 (2013.01); C07D 491/048 (2013.01); C07F 9/6506 (2013.01); C07F 9/65031 (2013.01)] 52 Claims
 
1. A compound, wherein the compound is of Formula I-a-4:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
Ring A is an optionally substituted heteroaryl ring, having 0 to 3 heteroatoms (in addition to the nitrogen already depicted in Ring A) independently selected from nitrogen, oxygen, phosphorus, and sulfur;
R2 is —NRR5, —NRaR5,

OG Complex Work Unit Chemistry
each R3 is independently halogen, —OMe, —OEt, —NR2, —SR, or RC;
Ring B1 is a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a benzotriazolyl, benzo[d]oxazol-2(3H)-one, benzo[d][1,3]dioxole, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, or indolizinyl ring;
Ring B2 is phenyl; a 4- to 7-membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
each R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic; benzyl; phenyl; a 4- to 7-membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
R5 is —(CR2)0-4OR, —(CR2)0-5CO2R, —(CR2)0-5CONR2, —(CR2)0-4C(O)NR(CR2)CO2R, —(CR2)0-4C(O)NR(CR2)0-4CONR2, —(CR2)0-4NRC(O)R, —(CR2)0-4SO3R, —(CR2)0-4SO2NR2, —(CR2)0-4OSO2NR2, —(CR2)0-4NRSO2R, —(CR2)0-4NRSO2OR, —(CR2)0-4OP(OR)2, —(CR2)0-4OP(O)(OR)2, —(CR2)0-4P(O)(OR)2, —(CR2)0-4OP(O)(H)OR, or RB;
each R6 is independently halogen, —CN, ═CH2, ═O, —C(O)NHOH, —C(O)N(CH3)OH, —C(O)N(CH3)OCH3, —C(O)NHSO2CHF2, —OCONHCH2CO2Me, —OCONHCH2CO2H, —NHCOCH2CH2CO2H, —NHCOCH2CH2CO2CH3, —COR, —(CR2)0-4CO2R, —(CR2)0-4CONR2, —OR, —(CR2)1-4OR, NR2, —(CR2)1-4NR2, —NRC(O)OR, —NRC(O)R, —NRC(O)NR2, —SR, —SO2R, —S(O)R, —(CR2)0-4SO3R, —(CR2)0-4SO2NR2, —(CR2)0-4OSO2NR2, —(CR2)0-4NRSO2R, —(CR2)0-4NRSO2OR, —(CR2)0-4OP(OR)2, —(CR2)0-4OP(O)(OR)2, —(CR2)0-4P(O)(OR)2, —(CR2)0-4OP(O)(H)OR, —B(OR)2,

OG Complex Work Unit Chemistry
or RB;
RB and RC, independently, are an optionally substituted group selected from C1-6 aliphatic; phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
each Ra is independently H or C1-6alkyl;
each m is 0, 1, 2, 3, or 4;
n is 1, 2, 3, or 4; and
q is 0, 1, or 2.