US 12,187,684 B2
Benzimidazole derivatives as modulators of retinoid-related orphan receptor gamma (RORγ) and pharmaceutical use thereof
Yinfa Yan, Bedminster, NJ (US); Minsheng Zhang, Warren, NJ (US); Dong Liu, Basking Ridge, NJ (US); Fengqi Zhang, Edison, NJ (US); Suxing Liu, Edison, NJ (US); Rumin Zhang, Edison, NJ (US); Feng He, Shanghai (CN); and Weikang Tao, North Brunswick, NJ (US)
Assigned to Jiangsu Hengrui Medicine Co., Ltd., Lianyungang (CN); and Shanghai Hengrui Pharmaceutical Co., Ltd., Shanghai (CN)
Filed by Jiangsu Hengrui Medicine Co., Ltd., Lianyungang (CN); and Shanghai Hengrui Pharmaceutical Co., Ltd., Shanghai (CN)
Filed on Nov. 21, 2022, as Appl. No. 18/057,537.
Application 18/057,537 is a continuation of application No. 17/052,451, granted, now 11,512,055, previously published as PCT/US2019/030526, filed on May 3, 2019.
Claims priority of provisional application 62/666,312, filed on May 3, 2018.
Prior Publication US 2023/0130361 A1, Apr. 27, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 235/06 (2006.01); C07D 235/12 (2006.01); C07D 235/14 (2006.01); C07D 235/16 (2006.01); C07D 401/04 (2006.01); C07D 409/04 (2006.01); C07D 413/12 (2006.01)
CPC C07D 235/06 (2013.01) [C07D 235/12 (2013.01); C07D 235/14 (2013.01); C07D 235/16 (2013.01); C07D 401/04 (2013.01); C07D 409/04 (2013.01); C07D 413/12 (2013.01)] 18 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:
custom character is a single bond or a double bond; when custom character is a double bond, then custom character is a single bond, Ra is absent, and Rb is hydrogen; and when custom character is a double bond, then custom character is single bond, Ra is hydrogen, and Rb is absent;
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 together form

OG Complex Work Unit Chemistry
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 is 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, 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 form a 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, 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.