Modulators of stimulator of interferon genes (STING)

A compound according to Formula (I):

• wherein:
• q is 0 or 1;
• r is 0 or 1;
• s is 0 or 1;
• wherein q+r+s=1 or 2;
• when q is 0, RA1 and RA2 are each independently H, halogen, hydroxy, —O—P(O)(OH)2, —O—P(O)(RI)(RII), —N(Re)(Rf), —CO2Rf, —N(Rf)CORb, —N(Rg)SO2(C1-C4alkyl)-N(Re)(Rf), —N(Rg)CO(C1-C4alkyl)-N(Rh)(Rf), optionally substituted (C1-C6alkyl), optionally substituted (C1-C6alkyl)oxy-, optionally substituted (C1-C6alkyl)amino-, and optionally substituted (C1-C6alkyl)(C1-C4alkyl)amino-,
• wherein the (C1-C6alkyl) of said optionally substituted (C1-C6alkyl), optionally substituted (C1-C6alkyl)oxy-, optionally substituted (C1-C6alkyl)amino- and optionally substituted (C1-C6alkyl)(C1-C4alkyl)amino- is optionally substituted by 1-4 substituents each independently selected from hydroxy, —O—P(O)(OH)2, —O—P(O)(RI)(RII), C1-C4alkoxy-, —N(Re)(Rf), —CO2(R), —CON(Re)(Rf), optionally substituted phenyl, optionally substituted 5-6 membered heterocycloalkyl and optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted by 1-4 substituents each independently selected from C1-C4alkyl, halogen, hydroxy, —O—P(O)(OH)2, —O—P(O)(RI)(RII), amino, (C1-C6alkyl)amino-, (C1-C6alkyl)(C1-C6alkyl)amino-, —(C1-C6alkyl)-NH2, halo(C1-C6alkyl), hydroxy-(C1-C4alkyl)-, —(C1-C4alkyl)-O—P(O)(OH)2, —(C1-C4alkyl)-O—P(O)(RI)(RII), halo(C1-C4alkoxy)-, C1-C4alkoxy-, hydroxy-(C2-C4alkoxy)-, —(C2-C4alkoxy)-O—P(O)(OH)2, —(C2-C4alkoxy)-O—P(O)(RI)(RII), —C1-C4alkyl-(C1-C4alkoxy) and C1-C4alkoxy-(C1-C4alkoxy)-;
• when r is 0, RB1 and RB2 are each independently H, optionally substituted C1-C6alkyl, halo(C1-C6alkyl), optionally substituted C2-C6alkenyl, optionally substituted C2-C6alkynyl, optionally substituted C3-C6cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl,
• wherein said optionally substituted C1-C6alkyl, optionally substituted C2-C6alkenyl, optionally substituted C2-C6alkynyl, optionally substituted C3-C6cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl is optionally substituted by 1-4 substituents each independently selected from halogen, nitro, —Rc, —OH, —O—P(O)(OH)2, —O—P(O)(RI)(RII), —ORc, —NH, —NRcRc, —NRcRd, —OCORc, —CO2H, —CO2Rc, —SORc, —SO2Rc, —CONH2, —CONRcRd, —SO2NH2, —SO2NRcRd, —OCONH2, —OCONRcRd, —NRdCORc, —NRdSORc, —NRdCO2Rc, and —NRdSO2Rc;
• when s is 0, RC1 is H, halogen, or C1-C4alkyl and RC2 is optionally substituted C1-C4alkyl, wherein said optionally substituted C1-C4alkyl group is optionally substituted by a substituent selected from —OR, —NRcRd, —CO2Rc, —CONRcRd, —SO2NRcRd, and —OCONRcRd;
• when q is 1, RA1 and RA2 are each independently —CH2—, —NRe—, or —O—, and A, taken together with RA1 and RA2, forms a linking group, wherein A is -halo(C1-C12alkyl)-, optionally substituted —C1-C12alkyl-, optionally substituted —C2-C12alkenyl-, optionally substituted —C2-C12alkynyl-, optionally substituted —C1-C6alkyl-O—C1-C6alkyl-, optionally substituted —C1-C6alkyl-NRa—C1-C6alkyl-, optionally substituted —C1-C6alkyl-(C3-C6cycloalkyl)-C1-C6alkyl-, optionally substituted —C1-C6alkyl-phenyl-C1-C6alkyl-, optionally substituted —C1-C6alkyl-(4-6 membered heterocycloalkyl)-C1-C6alkyl-, or optionally substituted —C1-C6alkyl-(5-6 membered heteroaryl)-C1-C6alkyl-,
• wherein the alkyl moiety of said optionally substituted —C1-C12alkyl-, optionally substituted —C2-C12alkenyl-, optionally substituted —C2-C12alkynyl-, optionally substituted —C1-C6alkyl-O—C1-C6alkyl-, optionally substituted —C1-C6alkyl-NRa—C1-C6alkyl-, optionally substituted —C1-C6alkyl-(C3-C6cycloalkyl)-C1-C6alkyl-, optionally substituted —C1-C6alkyl-phenyl-C1-C6alkyl-, optionally substituted —C1-C6alkyl-(4-6 membered heterocycloalkyl)-C1-C6alkyl-, or optionally substituted —C1-C6alkyl-(5-6 membered heteroaryl)-C1-C6alkyl- is optionally substituted by 1-4 substituents each independently selected from halogen, halo(C1-C4alkyl), —OH, —O—P(O)(OH)2, —O—P(O)(RI)(RII), —ORc, —NH2, —NRcRd, —OCORc, —CO2H, —CO2Rc, —SORc, —SO2Rc, —CONH2, —CONRcRd, —SO2NH2, —SO2NRcRd, —OCONH2, —OCONRcRd, —NRdCORc, —NRdSORc, —NRdCO2Rc, and —NRdSO2Rc,
• and
• the C3-C6cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted —C1-C6alkyl-(C3-C6cycloalkyl)-C1-C6alkyl-, optionally substituted —C1-C6alkyl-phenyl-C1-C6alkyl-, optionally substituted —C1-C6alkyl-(4-6 membered heterocycloalkyl)-C1-C6alkyl-, or optionally substituted —C1-C6alkyl-(5-6 membered heteroaryl)-C1-C6alkyl- is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, —O—P(O)(OH)2, —O—P(O)(RI)(RII), amino, (C1-C4alkyl)amino-, (C1-C4alkyl)(C1-C4alkyl)amino-, C1-C4alkyl, halo(C1-C4alkyl), halo(C1-C4alkoxy)-, C1-C4alkoxy-, hydroxy-(C1-C4alkoxy)-, —(C1-C4alkoxyl)-O—P(O)(OH)2, —(C1-C4alkoxyl)-O—P(O)(RI)(RII), and C1-C4alkoxy-(C1-C4alkoxy);
• when r is 1, RB1 and RB2 are each independently —CRdRf—, and B, taken together with RB1 and RB2, forms a linking group, wherein B is a bond or B is -halo(C1-C10alkyl)-, optionally substituted —C1-C10alkyl-, optionally substituted —C2-C10alkenyl-, optionally substituted —C2-C10alkynyl-, optionally substituted —C1-C6alkyl-O—C1-C6alkyl-, optionally substituted —C1-C6alkyl-NRa—C1-C6alkyl-, optionally substituted C3-C6cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted —C1-C4alkyl-(C3-C6cycloalkyl)-C1-C4alkyl-, optionally substituted —C1-C4alkyl-phenyl-C1-C4alkyl-, optionally substituted —C1-C4alkyl-(4-6 membered heterocycloalkyl)-C1-C4alkyl-, or optionally substituted —C1-C4alkyl-(5-6 membered heteroaryl)-C1-C4alkyl-,
• wherein the alkyl moiety of said optionally substituted —C1-C10alkyl-, optionally substituted —C2-C10alkenyl-, optionally substituted —C2-C10alkynyl-, optionally substituted —C1-C6alkyl-O—C1-C6alkyl-, optionally substituted —C1-C6alkyl-NRa—C1-C6alkyl-, optionally substituted —C1-C4alkyl-(C3-C6cycloalkyl)-C1-C4alkyl-, optionally substituted —C1-C4alkyl-phenyl-C1-C4alkyl-, optionally substituted —C1-C4alkyl-(4-6 membered heterocycloalkyl)-C1-C4alkyl-, or optionally substituted —C1-C4alkyl-(5-6 membered heteroaryl-C1-C4alkyl)- is optionally substituted by 1-4 substituents each independently selected from —C1-C4alkyl, halogen, halo(C1-C4alkyl), —OH, —O—P(O)(OH)2, —O—P(O)(RI)(RII), —ORc, —NH2, —NRcRd, —OCORc, —CO2H, —CO2Rc, —SORc, —SO2Rc, —CONH2, —CONRcRd, —SO2NH2, —SO2NRcRd, —OCONH2, —OCONRcRd, —NRdCORc, —NRdSORc, —NRdCO2Rc, and —NRdSO2Rc,
• and
• the C3-C6cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted C3-C6cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted —C1-C4alkyl-(C3-C6cycloalkyl)-C1-C4alkyl-, optionally substituted —C1-C4alkyl-phenyl-C1-C4alkyl-, optionally substituted —C1-C4alkyl-(4-6 membered heterocycloalkyl)-C1-C4alkyl-, or optionally substituted —C1-C4alkyl-(5-6 membered heteroaryl)-C1-C4alkyl- is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, —O—P(O)(OH)2, —O—P(O)(RI)(RII), amino, (C1-C4alkyl)amino-, (C1-C4alkyl)(C1-C4alkyl)amino-, C1-C4alkyl, halo(C1-C4alkyl), halo(C1-C4alkoxy)-, C1-C4alkoxy-, hydroxy-(C2-C4alkoxy)-, —(C2-C4alkoxy)O—P(O)(OH)2, —(C2-C4alkoxy)-O—P(O)(RI)(RII), and C1-C4alkoxy-(C1-C4alkoxy)-;
• when s is 1, RC1 and RC2 are each —CH2—, and C, taken together with RC1 and RC2, forms a linking group, wherein C is -halo(C1-C12alkyl)-, optionally substituted —C1-C12alkyl-, optionally substituted —C2-C12alkenyl-, optionally substituted —C2-C12alkynyl-, optionally substituted —C1-C6alkyl-O—C1-C6alkyl-, optionally substituted —C1-C6alkyl-NRa—C1-C6alkyl-, optionally substituted —C1-C6alkyl-(C3-C6cycloalkyl)-C1-C6alkyl-, optionally substituted —C1-C6alkyl-phenyl-C1-C6alkyl-, optionally substituted —C1-C6alkyl-(4-6 membered heterocycloalkyl)-C1-C6alkyl-, or optionally substituted —C1-C6alkyl-(5-6 membered heteroaryl)-C1-C6alkyl-,
• wherein the alkyl moiety of said optionally substituted —C1-C12alkyl-, optionally substituted —C2-C12alkenyl-, optionally substituted —C2-C12alkynyl-, optionally substituted —C1-C6alkyl-O—C1-C6alkyl-, optionally substituted —C1-C6alkyl-NRa—C1-C6alkyl-, optionally substituted —C1-C6alkyl-(C3-C6cycloalkyl)-C1-C6alkyl-, optionally substituted —C1-C6alkyl-phenyl-C1-C6alkyl-, optionally substituted —C1-C6alkyl-(4-6 membered heterocycloalkyl)-C1-C6alkyl-, or optionally substituted —C1-C6alkyl-(5-6 membered heteroaryl)-C1-C6alkyl- is optionally substituted by 1 or 2 substituents each independently selected from halogen, halo(C1-C4alkyl), —OH, —O—P(O)(OH)2, —O—P(O)(RI)(RII), —ORc, —NH2, —NRcRd, —OCORc, —CO2H, —CO2Rc, —SORc, —SO2Rc, —CONH2, —CONRcRd, —SO2NH2, —SO2NRcRd, —OCONH2, —OCONRcRd, —NRdCORc, —NRdSORc, —NRdCO2Rc, and —NRdSO2Rc,
• and
• the C3-C6cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted —C1-C6alkyl-(C3-C6cycloalkyl)-C1-C6alkyl-, optionally substituted —C1-C6alkyl-phenyl-C1-C6alkyl-, optionally substituted —C1-C6alkyl-(4-6 membered heterocycloalkyl)-C1-C6alkyl-, or optionally substituted —C1-C6alkyl-(5-6 membered heteroaryl)-C1-C6alkyl- is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, —O—P(O)(OH)2, —O—P(O)(RI)(RII), amino, (C1-C4alkyl)amino-, (C1-C4alkyl)(C1-C4alkyl)amino-, C1-C4alkyl, halo(C1-C4alkyl), halo(C1-C4alkoxy)-, C1-C4alkoxy-, hydroxy-(C2-C4alkoxy)-, —(C2-C4alkoxy)-O—P(O)(OH)2, —(C2-C4alkoxy)-O—P(O)(RI)(RII), and C1-C4alkoxy-(C1-C4alkoxy)-;
• R3 and R5 are each independently —CON(Rd)(Rf), or one of R3 and R5 is —CON(Rd)(Rf), and the other of R3 and R5 is H, COOH or —CO2(Rc);
• R4 and R6 are each independently selected from H, halogen, halo(C1-C6alkyl), halo(C1-C6alkoxy)-, hydroxy, —O—P(O)(OH)2, —O—P(O)(RI)(RII), —NH2, —NRcRc, —NRcRd—CORc, —CO2Rc, —N(Rd)CORc, —N(Rd)SO2Rc, —N(Rg)SO2(C1-C2alkyl)-N(Rh)(Rf), —N(Rg)CO(C1-C2alkyl)-N(Rh)(Rf), optionally substituted (C1-C6alkyl), optionally substituted (C1-C6alkyl)oxy-, optionally substituted (C1-C6alkyl)amino-, and optionally substituted (C1-C6alkyl)(C1-C4alkyl)amino-,
• wherein the (C1-C6alkyl) of said optionally substituted (C1-C6alkyl), optionally substituted (C1-C6alkyl)oxy-, optionally substituted (C1-C6alkyl)amino- and optionally substituted (C1-C6alkyl)(C1-C4alkyl)amino- is optionally substituted by 1-4 substituents each independently selected from —OH, —O—P(O)(OH)2, —O—P(O)(RI)(RII), —ORc, —NH2, —NRcRc, —NRcRd, —CO2H, —CO2Rc, —OCORc, —CO2H, —CO2Rc, —SORc, —SO2Rc, —CONH2, —CONRcRd, —SO2NH2, —SO2NRcRd, —OCONH2, —OCONRcRd, —NRdCORc, —NRdSORc, —NRdCO2Rc, —NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6 membered heterocycloalkyl and optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, —O—P(O)(OH)2, —O—P(O)(RI)(RII), amino, (C1-C4alkyl)amino-, (C1-C4alkyl)(C1-C4alkyl)amino-, C1-C4alkyl, halo(C1-C4alkyl), hydroxy-(C1-C4alkyl)-, —(C1-C4alkyl)-O—P(O)(OH)2, —(C1-C4alkyl)-O—P(O)(RI)(RII), halo(C1-C4alkoxy)-, C1-C4alkoxy-, hydroxy-(C2-C4alkoxy)-, —(C2-C4alkoxy)-O—P(O)(OH)2, —(C2-C4alkoxy)-O—P(O)(RI)(RII), C1-C4alkoxy-(C1-C4alkoxy)-, —CORd, —CON(Rd)(Rf), and —CO2Rd;
• R14 is optionally substituted C1-C4alkyl, wherein said optionally substituted C1-C4alkyl is optionally substituted by a substituent selected from —OR, —NRcRd, —CO2R, —CONRcRd, —SO2NRcRd, and —OCONRcRd;
• R16 is H, halogen, or C1-C4alkyl;
• R15 and R17 are each independently H, cyclopropyl, or C1-C4alkyl;
• Ra is H, —Rc, —CORc, —CO2H, —CO2Rc, —SORc, —SO2Rc, —CONH2, —CONRcRd, —SO2NH2, or —SO2NRcRd;
• each Rb is independently C1-C4alkyl, halo(C1-C4alkyl), —(C1-C4alkyl)-OH, —(C1-C4alkyl)-O—P(O)(OH)2, —(C1-C4alkyl)-O—P(O)(RI)(RII), —(C1-C4alkyl)-O—(C1-C4alkyl), —(C1-C4alkyl)-N(Re)(Rf), —(C1-C4alkyl)-O—CO(C1-C4alkyl), or —(C1-C4alkyl)-CO—O—(C1-C4alkyl);
• each Rc is independently C1-C4alkyl, halo(C1-C4alkyl), —(C1-C4alkyl)-OH, —(C1-C4alkyl)-O—P(O)(OH)2, —(C1-C4alkyl)-O—P(O)(RI)(RII), —(C1-C4alkyl)-O—(C1-C4alkyl), —(C1-C4alkyl)-N(Re)(Rf), —(C1-C4alkyl)-O—CO(C1-C4alkyl), —(C1-C4alkyl)-CO—O—(C1-C4alkyl), optionally substituted C3-C6cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted 9-10 membered heteroaryl, optionally substituted —C1-C4alkyl-C3-C6cycloalkyl, optionally substituted —C1-C4alkyl-phenyl, optionally substituted —C1-C4alkyl-4-6 membered heterocycloalkyl, optionally substituted —C1-C4alkyl-5-6 membered heteroaryl, or optionally substituted —C1-C4alkyl-9-10 membered heteroaryl,
• wherein the C3-C6cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl or optionally substituted 9-10 membered heteroaryl moiety of said substituted C3-C6cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted 9-10 membered heteroaryl optionally substituted —C1-C4alkyl-C3-C6cycloalkyl, optionally substituted —C1-C4alkyl-phenyl, optionally substituted —C1-C4alkyl-4-6 membered heterocycloalkyl, optionally substituted —C1-C4alkyl-5-6 membered heteroaryl, or optionally substituted —C1-C4alkyl-9-10 membered heteroaryl is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, —O—P(O)(OH)2, —O—P(O)(RI)(RII), amino, —(C1-C4alkyl)NH2, (C1-C4alkyl)amino-, (C1-C4alkyl)(C1-C4alkyl)amino-, —C1-C4alkyl, halo(C1-C4alkyl), halo(C1-C4alkoxy)-, C1-C4alkoxy-, hydroxy-(C2-C4alkoxy)-, —(C2-C4alkoxy)-O—P(O)(OH)2, —(C2-C4alkoxy)-O—P(O)(RI)(RII), C1-C4alkoxy-(C1-C4alkoxy)-, —CORd, —CON(Rd)(Rf), and —CO2Rd;
• each Rd is independently H or C1-C4alkyl;
• each Re is independently H, C1-C4alkyl, —CO(C1-C4alkyl), —OCO(C1-C4alkyl), —CO2(C1-C4alkyl), —(C1-C4alkyl)NH2, —(C1-C4alkyl) C1-C4alkoxy, —CO-(optionally substituted 5-6 membered heterocycloalkyl), —CO(C1-C4alkyl)-(optionally substituted 5-6 membered heterocycloalkyl), —CO (optionally substituted 5-6 membered heteroaryl), or —CO(C1-C4alkyl)-(optionally substituted 5-6 membered heteroaryl),
• wherein the optionally substituted 5-6 membered heterocycloalkyl or optionally substituted 5-6 membered heteroaryl is optionally substituted 1-4 substituents each independently selected from halogen, hydroxy, —O—P(O)(OH)2, —O—P(O)(RI)(RII), amino, (C1-C4alkyl)amino-, (C1-C4alkyl)(C1-C4alkyl)amino-, C1-C4alkyl, halo(C1-C4alkyl), halo(C1-C4alkoxy)-, C1-C4alkoxy-, hydroxy-(C2-C4alkoxy)-, —(C2-C4alkoxy) O—P(O)(OH)2, —(C2-C4alkoxy)-O—P(O)(RI)(RII), C1-C4alkoxy-(C1-C4alkoxy)-, —CORd, —CON(Rd)(Rf), and —CO2Rd;
• each Rf is independently H or C1-C4alkyl;
• Rg and Rh are each independently H or C1-C4alkyl or Rg and Rh, taken together with the atom or atoms through which they are connected, form a 5-6 membered ring;
• and each occurrence of RI and RII are independently (C1-C6alkyl)oxy-;
• one of RX and Ry is C1-C4alkyl and the other one is H,
• or both RX and Ry are independently C1-C4alkyl;
• or a tautomer thereof;
• or a salt thereof.