US 12,281,078 B2
Quinoline cGAS antagonist compounds
Qi Wei, Dallas, TX (US); Heping Shi, Coppell, TX (US); Matt Tschantz, Plano, TX (US); Jian Qiu, Dallas, TX (US); Youtong Wu, Dallas, TX (US); Huiling 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 Mar. 2, 2023, as Appl. No. 18/177,732.
Claims priority of provisional application 63/478,467, filed on Jan. 4, 2023.
Claims priority of provisional application 63/315,968, filed on Mar. 2, 2022.
Prior Publication US 2024/0002346 A1, Jan. 4, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 215/12 (2006.01); C07D 401/04 (2006.01); C07D 401/14 (2006.01); C07D 405/14 (2006.01); C07D 409/14 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01)
CPC C07D 215/12 (2013.01) [C07D 401/04 (2013.01); C07D 401/14 (2013.01); C07D 405/14 (2013.01); C07D 409/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01)] 26 Claims
 
1. A compound, wherein the compound is of Formula I:

OG Complex Work Unit Chemistry
or is a pharmaceutically acceptable salt thereof, wherein:
Ring A is optionally substituted HetCy, wherein substitution
(a) when on a substitutable carbon atom, is with one or more groups selected from halogen; —(CH2)0-6R∘; —(CH2)0-6OR∘; —O(CH2)0-6R∘; —O—(CH2)0-6C(O)OR∘; —(CH2)0-6CH(OR∘)2; —(CH2)0-6SR∘; —(CH2)0-6Ph, which Ph may be substituted with R∘; —(CH2)0-6(CH2)0-1Ph which Ph may be substituted with R∘; —CH═CHPh, which Ph may be substituted with R∘; —(CH2)0-6O(CH2)0-1-pyridyl which pyridyl may be substituted with R∘; —NO2; —CN; —N3; —(CH2)0-6N(R∘)2; —(CH2)0-6N(R∘)C(O)R∘; —N(R∘)C(S)R∘; —(CH2)0-6N(R∘)C(O)NR∘2; —N(R∘)C(S)NR∘2; —(CH2)0-6N(R∘)C(O)OR∘; —N(R∘)N(R∘)C(O)R∘; —N(R∘)N(R∘)C(O)NR∘2; —N(R∘)N(R∘)C(O)OR∘; —(CH2)0-6C(O)R∘; —C(S)R∘; —(CH2)0-6C(O)OR∘; —(CH2)0-6C(O)SR∘; —(CH2)0-6C(O)OSiR∘3; —(CH2)0-6OC(O)R∘; —OC(O)(CH2)0-6SR∘, —(CH2)0-6SC(O)R∘; —(CH2)0-6C(O)NR∘2; —C(S)NR∘2; —C(S)SR∘; —SC(S)SR∘, —(CH2)0-6OC(O)NR∘2; —C(O)N(OR∘)R∘; —C(O)C(O)R∘; —C(O)CH2C(O)R∘; —C(NOR∘)R∘; —(CH2)0-6SSR∘; —(CH2)0-6S(O)2R∘; —(CH2)0-6S(O)2OR∘; —(CH2)0-6OS(O)2R∘; —S(O)2NR∘2; —(CH2)0-6S(O)R∘; —N(R∘)S(O)2NR∘2; —N(R∘)S(O)2R∘; —N(OR∘)R∘; —C(NH)NR∘2; —P(O)2R∘; —P(O)R∘2; —P(O)(OR∘)2; —OP(O)(R∘)OR∘; —OP(O)R∘2; —OP(O)(OR∘)2; SiR∘3; —(C1-4 straight or branched alkylene)O—N(R∘)2; or —(C1-4 straight or branched alkylene)C(O)O—N(R∘)2, wherein each R∘ is independently hydrogen, C1-6 aliphatic, —CH2Ph, —O(CH2)0-1Ph, or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; ═O, ═S, ═NNR*2, ═NNHC(O)R*, ═NNHC(O)OR*, ═NNHS(O)2R*, ═NR*, ═NOR*, —O(C(R*2))2-3O—, or —S(C(R*2))2-3S—, wherein each independent occurrence of R* is selected from hydrogen, C1-6 aliphatic or an unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or
(b) when on a substitutable nitrogen atom, is with one or more groups selected from —R†, —NR†2, —C(O)R†, —C(O)OR†, —C(O)C(O)R†, —C(O)CH2C(O)R†, —S(O)2R†, —S(O)2NR†2, —C(S)NR†2, —C(NH)NR†2, or —N(RT)S(O)2R†, wherein each RT is independently hydrogen, C1-6 aliphatic, —OPh, or an unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
HetCy is a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
R2 is

OG Complex Work Unit Chemistry
each R3 is independently halogen, —OR, —NR2, or —SR, wherein at least one occurrence of R3 is halogen;
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 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
Ring B2 is 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 10-membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur, or:
two R groups on the same nitrogen are optionally taken together with their intervening atoms to form an optionally substituted 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, phosphorus, and sulfur;
R5 is —(CR2)0-4OR, —(CR2)0-5CO2R, —(CR2)0-5CONR2, —(CR2)0-4C(O)NR(CR2)0-4CO2R, —(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, —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, or RB;
RB is an optionally substituted group selected from C1-6 aliphatic; phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carboxylic 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 1, 2, 3, or 4;
n is 1, 2, 3, or 4;
q is 1 or 2;
provided that the compound is not:

OG Complex Work Unit Chemistry