Highly active sting protein agonist compound

A compound having a structure of Formula (I) or (II),

• wherein W1 represents (CRaRa′)s, any one CRaRa′ is optionally substituted by 0, 1 or 2 O, S or NRb, or any one CRaRa′ is optionally taken together to form —C═O;
• W2 represents (CRhRh′)t, wherein any one CRhRh′ is optionally substituted by 0, 1 or 2 O, S or NR, or any one CRhRh′ is optionally taken together to form —C═O:
• s and t each independently consist of an integer selected from 1, 2, and 3;
• q is selected from 0 and 1;
• r is selected from 0 and 1;
• and
• q and r are not 0 at the same time;
• wherein R1, R2, R3, and R4 each independently represent hydrogen, halogen, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —ORc, —O—(C1-C6 alkylene)-NRcRc′, —NRcRc′, —OC(O)Rc, —C(O)Rc, —CO2R, —CON(Rc)(Rc′), —C(═NH)N(Rc)(Rc′), —NRcC(O)Rc′, —SO2Rc, —SO2NRcRc′, —N(Rc)—SO2—(C1-C6 alkyl)-NRcRc′, —N(Rc)—C(O)—(C1-C6 alkyl)-NRcRc′, —NRcS(O)Rc′, —NRcSO2Rc′, —O—P(O)(ORc)(ORc′), 6- to 12-membered aryl or 5- to 12-membered heteroaryl;
• R5 and R6 are each independently selected from hydrogen or C1-C6 alkyl;
• wherein when q=0, QA1 is each independently selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —(C0-C6 alkyl)-(C3-C6 cycloalkyl), —(C0-C6 alkyl)-(4- to 6-membered heterocyclyl), —(C0-C6 alkyl)-(6- to 12-membered aryl), and —(C0-C6 alkyl)-(5- to 12-membered heteroaryl);
• or QA1 and R5 together with atoms adjacent thereto form a 3- to 6-membered ring optionally containing 0, 1 or 2 heteroatoms selected from O, N and S;
• QA2 is each independently selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —(C0-C6 alkyl)-(C3-C6 cycloalkyl), —(C0-C6 alkyl)-(4- to 6-membered heterocyclyl), —(C0-C6 alkyl)-(6- to 12-membered aryl), and —(C0-C6 alkyl)-(5- to 12-membered heteroaryl);
• or QA2 and R6 together with atoms adjacent thereto, form a 3- to 6-membered ring optionally containing 0, 1, or 2 heteroatoms selected from O, N, and S:
• when q=1, -QA1-A-QA2- is taken together to form a linking group selected from:
• —C1-C6 alkylene-, —C2-C6 alkenylene-, —C2-C6 alkynylene-, —(C0-C6 alkylene)-O—(C0-C6 alkylene)-, —(C0-C6 alkylene)-C(O)—(C0-C6 alkylene)-, —C(O)—(C0-C6 alkylene)-O—(C0-C6 alkylene)-, —(C0-C6 alkylene)-OC(O)—(C0-C6 alkylene)-, —(C0-C6 alkylene)-NRc—C(O)—(C0-C6 alkylene)-, —(C0-C6 alkylene)-C(O)—NRc—(C0-C6 alkylene)-, —(C0-C6 alkylene)-NRc—(C0-C6 alkylene)-, —(C0-C6 alkylene)-C(O)O—(C0-C6 alkylene)-, —(C0-C6 alkylene)-(C3-C6 carbocyclyl)-(C0-C6 alkylene)-, —(C0-C6 alkylene)-(4- to 6-membered heterocyclyl)-(C0-C6 alkylene)-, —(C0-C6 alkylene)-(6- to 12-membered aryl)-(C0-C6 alkylene)-, and —(C0-C6 alkylene)-(5- to 12-membered heteroaryl)-(C0-C6 alkylene)-;
• wherein when r=0, QB1 and QB2 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —(C0-C6 alkyl)-(C3-C6 cycloalkyl), —(C0-C6 alkyl)-(4- to 6-membered heterocyclyl), —(C0-C6 alkyl)-(6- to 12-membered aryl), and —(C0-C6 alkyl)-(5- to 12-membered heteroaryl);
• when r=1, -QB1-B-QB2- is taken together to form a linking group selected from:
• —C1-C6 alkylene-, —C2-C6 alkenylene-, —C2-C6 alkynylene-, —(C0-C6 alkylene)-O—(C0-C6 alkylene)-, —(C0-C6 alkylene)-C(O)—(C0-C6 alkylene)-, —C(O)—(C0-C6 alkylene)-O—(C0-C6 alkylene)-, —(C0-C6 alkylene)-OC(O)—(C0-C6 alkylene)-, —(C0-C6 alkylene)-NRc—C(O)—(C0-C6 alkylene)-, —(C0-C6 alkylene)-C(O)—NRc—(C0-C6 alkylene)-, —(C0-C6 alkylene)-NRc—(C0-C6 alkylene)-, —(C0-C6 alkylene)-C(O)O—(C0-C6 alkylene)-, —(C0-C6 alkylene)-(C3-C6 carbocyclyl)-(C0-C6 alkylene)-, —(C0-C6 alkylene)-(4- to 6-membered heterocyclyl)-(C0-C6 alkylene)-, —(C0-C6 alkylene)-(6- to 12-membered aryl)-(C0-C6 alkylene)-, and —(C0-C6 alkylene)-(5- to 12-membered heteroaryl)-(C0-C6 alkylene)-;
• RI and RII each independently represent hydrogen or C1-C6 alkyl;
• wherein Ra, Ra′, Rh and Rh′ each independently represent hydrogen, halogen, hydroxy, C1-C6 alkyl, C1-C6 alkylthio, —(C0-C6 alkylene)-(C3-C6 cycloalkyl), —(C0-C6 alkylene)-(4- to 6-membered heterocyclyl), —(C0-C6 alkylene)-(6- to 12-membered aryl), —(C0-C6 alkylene)-(5- to 12-membered heteroaryl), —NRdRd′, —NRdCORd′, —NRdS(O)Rd′, —NRdSO2Rd′, —OR, or —OCORd;
• Rb and Rj each independently represent hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, —(C0-C6 alkylene)-(6- to 12-membered aryl), —C(O)Re, —SORe, —SO2Re, —C(O)ORe, or —C(O)NReRe′;
• Rc and Rc′ each independently represent hydrogen, C1-C6 alkyl, —(C0-C6 alkylene)-(C3-C6 cycloalkyl), or —(C0-C6 alkylene)-(4- to 6-membered heterocyclyl);
• or Ra and Ra′ together with the atom bound thereto are optionally cyclized to each other into a 3- to 6-membered ring optionally containing 0, 1, or 2 heteroatoms selected from O, N and S;
• or Rc and Rc′ together with the atom bound thereto are optionally cyclized to each other into a 3- to 6-membered ring optionally containing 0, 1, or 2 heteroatoms selected from O, N and S;
• or Rh and Rh′ together with the atom bound thereto are optionally cyclized to each other into a 3- to 6-membered ring optionally containing 0, 1, or 2 heteroatoms selected from O, N and S:
• wherein m=1, 2, 3 or 4;
• n=1, 2 or 3;
• o=1 or 2;
• and
• p=1 or 2;
• or when m=2, the two adjacent R1 and the atom bound thereto are optionally cyclized to each other into a 5- to 8-membered ring optionally containing 0, 1 or 2 heteroatoms selected from O, N and S;
• or when n=2, the two adjacent R2 and the atom bound thereto are optionally cyclized to each other into a 5- to 8-membered ring optionally containing 0, 1 or 2 heteroatoms selected from O, N and S;
• or when p=2, the two adjacent R4 and the atom bound thereto are optionally cyclized to each other into a 5- to 8-membered ring optionally containing 0, 1 or 2 heteroatoms selected from O, N and S;
• any alkyl, alkoxy, alkenyl, alkynyl, alkylene, aryl, heteroaryl, carbocyclyl, heterocyclyl defined above are optionally substituted by 0, 1, 2, 3, or 4 substituents selected from:
• C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, sulfo, cyano, 3- to 8-membered carbocyclyl, 3- to 8-membered heterocyclyl, 6- to 12-membered aryl, 5- to 12-membered heteroaryl, nitro, oxo, C1-C6 mercapto, C1-C6 alkoxy, —ORf, —C(O)—ORf, —OC(O)Rf, —S(O)Rf, —S(O)2Rf, —S(O)2NRfRf′, —OCONRfRf′, —NRfCORf′, —NRfS(O)Rf′, —NRfS(O)2Rf′, —NRfC(O)ORf′, —CONRfRf′, —NRfRf′, —NHC═NHNRfRf′, C1-C6 haloalkyl, C1-C6 haloalkoxy, and —O—P(O)(ORf)(ORf′);
• wherein Rd, Rd′, Re, Re′, Rf, and Rf′ each independently represent hydrogen or C1-C6 alkyl, wherein the C1-C6 alkyl is also optionally substituted by C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, sulfo, cyano, 3- to 8-membered carbocyclyl, 3- to 8-membered heterocyclyl, 6- to 12-membered aryl, 5- to 12-membered heteroaryl, nitro, oxo, C1-C6 mercapto, C1-C6 alkoxy, —ORg, —C(O)—ORg, —OC(O)Rg, —S(O)Rg, —S(O)2Rg, —S(O)2NRgRg′, —NRgCORg′, —NRgS(O)Rg′, —NRgS(O)2Rg′, —NRgC(O)ORg′, —CONRgRg′, —NRgRg′, C1-C6 haloalkyl, C1-C6 haloalkoxy, or —O—P(O)(ORg)(ORg′);
• or Rd, Rd′, Re, Re′, Rf, and Rf′ together with the nitrogen atom bound thereto form a 5- to 8-membered carbocycle or a 5- to 8-membered heterocycle;
• wherein Rg and Rg′ are each independently selected from hydrogen or C1-C6 alkyl.