cGAS antagonist compounds

A compound, wherein the compound is one of Formula Ic:

• wherein:
• X is NH or S;
• Y is O or S;
• Z is O, S, CHR1a or NR1a;
• wherein 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 groups;
• G is N or C;
• if G is N, then R1 is C1-6alkyl or C1-6alkyl selectively functionalized with one or more halogen, thiol, hydroxyl, carbonyl, carbonyloxyl, C1-6alkoxy, C1-6hydroxyalkoxy, amino, C1-6alkylamino, di(C1-6alkyl)amino, or azido groups, or R1-R1a are connected as a —CH2CH2—, —CH2CH2CH2—, —CH═CH—, —C(CH3)═CH— or —CH═C(CH3)— group;
• and
• if G is C, then Z includes R1a and R1-R1a are connected as a ═CH—CH═CH—, ═N—CH═CH—, or ═CH—N═CH— group;
• W is OR10a or NHR10a;
• wherein R10a 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 groups, or R10a-R6 are connected as a —CH2—CH2—, —CH═CH—, —N═CH—, or —CH═N— group;
• 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 groups;
• R3 is halogen, —SR3a, —S(O)R3a, —OR3a, —OCH2R3b, —OCH(CH3)R3b, —OC(O)NHR3a, —NR3aR4a, —NHSO2R3a, azido, —CHO, —CO2R3a, cyano, C1-6alkyl, —CR5aR6aR7a, C2-6alkenyl, —C(R5a)═C(R8a)(R9a), C2-6alkynyl, —C≡CR8a, or R2—R3 are connected as a —CH2CH2—or —CH2CH2CH2— group;
• wherein R3a, R3b, and R4a are independently hydrogen, phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, tetrazolyl groups, 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 groups are optionally substituted with 1-3 substituents independently selected from the group consisting of 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 groups 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 groups;
• wherein R5a, R6a, R7a, R8a, and R9a are independently hydrogen, phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, tetrazolyl groups, C1-6alkyl, cyclic-(C1-8alkyl)-, cyclic-(C1-6oxaalkyl)-, cyclic-(C1-6azaalkyl)-, C2-6alkenyl, C2-6alkynyl, C1-6alkoxyl, cyclic-(C1-8alkoxyl)-, cyclic-(C1-6oxaalkoxyl)-, or cyclic-(C1-6azaalkoxyl)-;
• wherein the phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, or thiazolyl, tetrazolyl groups are optionally substituted with 1-3 substituents independently selected from the group consisting of 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 groups;
• and the C1-6alkyl, cyclic-(C1-8alkyl)-, cyclic-(C1-6oxaalkyl)-, cyclic-(C1-6azaalkyl)-, C2-6alkenyl, or C2-6alkynyl groups are selectively functionalized with one or more halogen, thiol, hydroxyl, carbonyl, carboxyl, carbonyloxyl, C1-6alkoxy, C1-6 hydroxyalkoxy, amino, C1-6alkylamino, di(C1-6alkyl)amino, azido, piperidinyl, phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, or tetrazolyl groups;
• R6 is hydrogen, halogen, —SR3a, —S(O)R3a, —OR3a, —OCH2R3b, —OCH(CH3)R3b, —OC(O)NHR3a, —NR3aR4a, —NHSO2R3a, azido, —CHO, CO2R3a, cyano, C1-6alkyl, —CR5aR6aR7a, C2-6alkenyl, —C(R5a)═C(R8a)(R9a), C2-6alkynyl, or —C≡CR8a;
• wherein R3a, R3b, and R4a are independently hydrogen, phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3-triazolyl, quinolinyl, isoquinolinyl, thiazolyl, tetrazolyl groups, 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 groups are optionally substituted with 1-3 substituents independently selected from the group consisting of 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 groups 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, quinolinyl, isoquinolinyl, thiazolyl, or tetrazolyl groups;
• wherein R5a, R6a, R7a, R8a, and R9a are independently hydrogen, phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3—triazolyl, quinolinyl, isoquinolinyl, thiazolyl, tetrazolyl groups, C1-6alkyl, cyclic—(C1-8alkyl)—, cyclic—(C1-6oxaalkyl)—, cyclic—(C1-6azaalkyl)—, C2-6alkenyl, C2-6alkynyl, C2-6alkynyl, C1-6alkoxyl, cyclic—(C1-8alkoxyl)—, cyclic—(C1-6oxaalkoxyl)—, or cyclic—(C1-6azaalkoxyl)—;
• wherein the phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, 1,2,3—triazolyl, quinolinyl, isoquinolinyl, or thiazolyl, tetrazolyl groups are optionally substituted with 1-3 substituents independently selected from the group consisting of halogen, thiol, C1-6alkyl thioether, C1-6alkyl sulfoxide, C1-6alkyl, C1-6alkoxyl, amino, C1-6alkylamino, C1-6diakylamino, C1-6alkyl sulfonamide, azido, —CHO, —CO2H, C1-6alkyl carboxylate, cyano, C2-6alkenyl, and C2-6alkynyl groups;
• and the C1-6alkyl, cyclic—(C1-8alkyl)—, cyclic—(C1-6oxaalkyl)—, cyclic—(C1-6azaalkyl)—, C2-6alkenyl, or C2-6alkynyl groups 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 groups;
• R4 is hydrogen or halogen;
• or a pharmaceutically acceptable salt thereof.