Benzimidazole Derivatives as Modulators of Retinoid-Related Orphan Receptor Gamma (RORy) and Pharmaceutical Uses Thereof

A compound of formula (IA):

• or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt, solvate, or prodrug thereof,
• wherein:
• is a single bond or double bond;
• when
• is a double bond, then
• is a single bond, Ra is absent, and Rb is hydrogen;
• and when
• is a double bond, then
• is single bond, Ra is hydrogen, and Rb is absent;
• R1, R2, and R3 are each independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, cyano, amino, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R5a and R5b are each independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, hydroxy, hydroxyalkyl, alkoxy, cyano, amino, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR8, —(CH2)xNR10COR9, —NR10COR9, —NR10COCH2OR8, —(CH2)xC(O)OR8, —(CH2)xCONR11R12, and —(CH2)xNR11R12, wherein said alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, —CONR11R12, —NR10COR9, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• or R5a and R5b are together form
• R6 is selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and —NR11R12, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R7 at each occurrence is independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, cyano, amino, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR8, —C(O)OR8, —COR9, —NR10COR9, —S(O)2R9, —NR10S(O)2R9, —CONR11R12, —NR11R12, and —S(O)2NR11R12, wherein said alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more group(s) selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R8 is selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, and heterocyclyl, wherein said alkyl, aryl, and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen and alkoxy;
• R9 is selected from the group consisting of hydrogen, alkyl, hydroxyl, alkoxy, cycloalkyl, aryl, and heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R10 is selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, and heterocyclyl;
• R11 and R12 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, heterocyclyl, COR13, aryl, and heteroaryl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• or R11 and R12 together with the nitrogen atom to which they are attached forma heterocyclyl group, wherein the heterocyclyl group comprises one or more additional heteroatoms independently selected from the group consisting of O, N and S, and wherein the heterocyclyl group is optionally substituted by one or more groups independently selected from the group consisting of alkyl, haloalkyl, halogen, amino, nitro, cyano, hydroxy, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R13 is selected from the group consisting of hydrogen, alkyl, hydroxyl, alkoxy, cycloalkyl, aryl, and heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more groups independently selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• n is 0, 1, 2, 3, or 4;
• and x is 0, 1, 2, 3 or 4.

A compound of formula (IC) or formula (ID), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt, solvate, or prodrug thereof,

• wherein:
• Ra and Rb is hydrogen;
• ring A is selected from the group consisting of cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R1, R2, and R3 are each independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, cyano, amino, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R4 at each occurrence is independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, haloalkoxy, cyano, amino, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR8, —C(O)OR8, —COR9, —NR10COR9, —S(O)2R9, —NR10S(O)2R9, —CONR11R12, —NR11R12, and —S(O)2NR11R12, wherein said alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more groups independently selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R5a and R5b are each independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, hydroxy, hydroxyalkyl, alkoxy, cyano, amino, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR8, —(CH2)xNR10COR9, —NR10COR9, —NR10COCH2OR8, —(CH2)xC(O)OR8, —(CH2)xCONR11R12, and —(CH2)xNR11R12, wherein said alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, —CONR11R12, —NR10COR9, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• or R5a and R5b are together form
• R6 is selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and —NR11R12, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R7 at each occurrence is independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, cyano, amino, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR8, —C(O)OR8, —COR9, —NR10COR9, —S(O)2R9, —NR10S(O)2R9, —CONR11R12, —NR11R12, and —S(O)2NR11R12, wherein said alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more group(s) selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R8 is selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, and heterocyclyl, wherein said alkyl, aryl, and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen and alkoxy;
• R9 is selected from the group consisting of hydrogen, alkyl, hydroxyl, alkoxy, cycloalkyl, aryl, and heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R10 is selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, and heterocyclyl;
• R11 and R12 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, heterocyclyl, COR13, aryl, and heteroaryl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• or R11 and R12 together with the nitrogen atom to which they are attached forma heterocyclyl group, wherein the heterocyclyl group comprises one or more additional heteroatoms independently selected from the group consisting of O, N and S, and wherein the heterocyclyl group is optionally substituted by one or more groups independently selected from the group consisting of alkyl, haloalkyl, halogen, amino, nitro, cyano, hydroxy, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• R13 is selected from the group consisting of hydrogen, alkyl, hydroxyl, alkoxy, cycloalkyl, aryl, and heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted by one or more groups independently selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, nitro, hydroxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• n is 0, 1, 2, 3, or 4;
• s is 0, 1, 2, 3 or 4;
• and
• x is 0, 1, 2, 3 or 4.