CGAS antagonist compounds

A compound of Formula Ia, or a pharmaceutically acceptable salt, solvate, stereoisomer, tautomer, or prodrug thereof,

• wherein:
• X is NH or S;
• Y is O or S;
• Z is O, S, CHR1a or NR1a;
• R1a is hydrogen, C1-6alkyl, or C1-6alkyl selectively functionalized with one or more halogen, thiol, hydroxyl, carbonyl, carboxyl, carbonyloxyl, C1-6alkoxy, C1-6hydroxyalkoxy, amino, C1-6alkylamino, di(C1-6alkyl)amino, or azido;
• G is N or C;
• if G is N, R1 is hydrogen C1-6alkyl, or C1-6alkyl selectively functionalized with one or more halogen, thiol, hydroxyl, carbonyl, carboxyl, carbonyloxyl, C1-6alkoxy, C1-6hydroxyalkoxy, amino, C1-6alkylamino, di(C1-6alkyl)amino, or azido,
• if G is N and if Z includes R1a, R1-R1a is connected as a —CH2CH2—, —CH2CH2CH2—, —CH═CH—, —C(CH3)═CH— or —CH═C(CH3)—;
• and
• if G is C and if Z includes R1a, R1-R1a is connected as a ═CH—CH═CH—, ═N—CH═CH—, or ═CH—N═CH—;
• R1 is hydrogen or C1-6alkyl, or R1-R1a are connected form a —CH2CH2—, —CH2CH2CH2—, —CH═CH—, —C(CH3)═CH—, or —CH═C(CH3)— or together with carbon or nitrogen atoms to which they are attached form a pyridine, pyrimidine or pyrazine ring;
• R2 is hydrogen, halogen, C1-6alkyl, or C1-6alkyl selectively functionalized with one or more halogen, thiol, hydroxyl, carbonyl, carboxyl, carbonyloxyl, C1-6alkoxy, C1-6hydroxyalkoxy, amino, C1-6alkylamino, di(C1-6alkyl)amino, or azido;
• R2a is phenyl or heteroaryl, wherein the phenyl or heteroaryl is substituted with 1-4 substituents independently selected from halogen, —SR3a, —S(O)R3a, —OR3a, —OCH2R3b, —OCH(CH3)R3b, —OC(O)NHR3a, —NR3aR4a, —NHSO2R3a, azido, —CHO, —CO2R3a, cyano, C1-6alkyl or —CR5aR6aR7a, C2-6alkenyl, —C(R5a)═C(R8a)(R9a), C2-6alkynyl, and —C≡CR8a;
• wherein
• R3a, R3b, and R4a are independently hydrogen, phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, tetrazolyl, C1-6alkyl, cyclic —(C1-8alkyl)-, cyclic —(C1-6oxaalkyl)-, cyclic —(C1-6azaalkyl)-, C2-6alkenyl, or C2-6alkynyl;
• wherein the phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, or tetrazolyl are optionally substituted with 1-3 substituents independently selected from halogen, thiol, C1-6alkyl thioether, C1-6alkyl sulfoxide, C1-6alkyl, C1-6alkoxyl, amino, C1-6alkylamino, C1-6dialkylamino, C1-6alkyl sulfonamide, azido, —CHO, —CO2H, C1-6alkyl carboxylate, cyano, C2-6alkenyl, and C2-6alkynyl group;
• and the C1-6alkyl, cyclic —(C1-8alkyl)-, cyclic —(C1-6oxaalkyl)-, cyclic —(C1-6azaalkyl)-, C2-6alkenyl, or C2-6alkynyl are selectively functionalized with one or more halogen, thiol, hydroxyl, carbonyl, carboxyl, carbonyloxyl, C1-6alkoxy, C1-6hydroxyalkoxy, amino, C1-6alkylamino, di(C1-6alkyl)amino, azido, piperidinyl, phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, or tetrazolyl;
• R5a, R6a, R7a, R8a and R9a are independently hydrogen, phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, tetrazolyl, C1-6alkyl, cyclic —(C1-8alkyl)-, cyclic —(C1-6oxaalkyl)-, cyclic —(C1-6azaalkyl)-, C2-6alkenyl, C2-6alkynyl, C1-6alkoxyl, cyclic —(C1-8alkoxyl)-, cyclic —(C1-6oxaalkoxyl)-, cyclic —(C1-6azaalkoxyl)-;
• wherein the phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, or tetrazolyl are optionally substituted with 1-3 substituents independently selected from halogen, thiol, C1-6alkyl thioether, C1-6alkyl sulfoxide, C1-6alkyl, C1-6alkoxyl, amino, C1-6alkylamino, C1-6dialkylamino, C1-6alkyl sulfonamide, azido, —CHO, —CO2H, C1-6alkyl carboxylate, cyano, C2-6alkenyl, and C2-6alkynyl, and the C1-6alkyl, cyclic —(C1-8alkyl)-, cyclic —(C1-6oxaalkyl)-, cyclic —(C1-6azaalkyl)-, C2-6alkenyl, or C2-6alkynyl are selectively functionalized with one or more halogen, thiol, hydroxyl, carbonyl, carboxyl, carbonyloxyl, C1-6alkoxy, C1-6hydroxyalkoxy, amino, C1-6alkylamino, di(C1-6alkyl)amino, azido, piperidinyl, phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, or tetrazolyl;
• and
• the phenyl or heteroaryl that is R2a is substituted at least with —OCH2R3b or —OCH(CH3)R3b, wherein R3b is phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, tetrazolyl, cyclic —(C1-8alkyl)-, cyclic —(C1-6oxaalkyl)-, or cyclic —(C1-6azaalkyl)-;
• wherein the phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, or tetrazolyl are optionally substituted with 1-3 substituents independently selected from halogen, thiol, C1-6alkyl thioether, C1-6alkyl sulfoxide, C1-6alkyl, C1-6alkoxyl, amino, C1-6alkylamino, C1-6dialkylamino, C1-6alkyl sulfonamide, azido, —CHO, —CO2H, C1-6alkyl carboxylate, cyano, C2-6alkenyl, and C2-6alkynyl group;
• and the cyclic —(C1-8alkyl)-, cyclic —(C1-6oxaalkyl)-, or cyclic —(C1-6azaalkyl)- are selectively functionalized with one or more halogen, thiol, hydroxyl, carbonyl, carboxyl, carbonyloxyl, C1-6alkoxy, C1-6hydroxyalkoxy, amino, C1-6alkylamino, di(C1-6alkyl)amino, azido, piperidinyl, phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, or tetrazolyl.