Substituted 1,2,4-triazoles and methods of use

A method of treating or preventing cancer caused by and/or associated with deregulation of one or more of a STimulator of Interferon Genes (STING) intracellular pathways in a patient comprising:

• (a) determining from a patient test sample that one or more of the STING intracellular pathways is deregulated in the patient;
• and
• (b) administering to the patient a therapeutically effective amount of a compound of Formula Ig:
• or a
• pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof,
• or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, where:
• R1a is independently (C1-C6) alkyl, (C3-C6) cycloalkyl, (C1-C6) haloalkyl, (C1-C6) alkoxy, (C1-C6) haloalkoxy, (C2-C6) alkenyl, (C2-C6) alkynyl, halogen, nitro, CN, oxo, B(OH)2, OH, COOH, SH, NH2, NH(C1-C4) alkyl, or N((C1-C4) alkyl)2;
• R2 is H, SO2—(C1-C12)-alkyl, or (C5-C10) aryl, where the alkyl or aryl is optionally substituted by OH, alkoxy, or halogen;
• R4 is independently H, (C5-C10) aryl, (C5-C10) cycloalkyl, (C5-C10) heteroaryl, or 5- to 14-membered heterocyclyl comprising 1-5 heteroatoms selected from N, O and S, where the aryl, heteroaryl, or heterocyclyl is optionally substituted with one or more (C5-C10) aryl, (C1-C6) alkyl, (C3-C6) cycloalkyl, (C1-C6) haloalkyl, (C1-C6) alkoxy, (C1-C6) haloalkoxy, (C2-C6) alkenyl, (C2-C6) alkynyl, halogen, nitro, —CN, oxo, —B(OH)2, —OH, —COOH, —SH, —NH2, —NH(C1-C4)
• alkyl, —N((C1-C4) alkyl)2, or —(CH2)nNC(O)(C1-C4) alkyl, where n is 0, 1, 2, or 3;
• R5 is H, (C1-C6) alkyl, or (C5-C10) aryl, where the alkyl, or aryl is optionally substituted with (C5-C10) aryl, (C1-C6) alkyl, (C1-C6) alkoxy, (C3-C6) cycloalkyl, (C1-C6) haloalkyl, (C1-C6) alkoxy, halogen, or oxo, m is 0, 1, 2, 3, 4 or 5 and where p is 0, 1, 2, 3, 4, or 5.