US 11,739,065 B2
FXR (NR1H4) modulating compounds
Peter A. Blomgren, Issaquah, WA (US); Kevin S. Currie, North Bend, WA (US); Christian Gege, Ehingen (DE); Jeffrey E. Kropf, Issaquah, WA (US); and Jianjun Xu, Bellevue, WA (US)
Assigned to Gilead Sciences, Inc., Foster City, CA (US)
Filed by Gilead Sciences, Inc., Foster City, CA (US)
Filed on Nov. 29, 2021, as Appl. No. 17/537,250.
Application 17/537,250 is a continuation of application No. 17/217,781, filed on Mar. 30, 2021, abandoned.
Application 17/217,781 is a continuation of application No. 16/989,335, filed on Aug. 10, 2020, granted, now 10,981,881, issued on Apr. 20, 2021.
Application 16/989,335 is a continuation of application No. 16/541,073, filed on Aug. 14, 2019, granted, now 10,774,054, issued on Sep. 15, 2020.
Application 16/541,073 is a continuation of application No. 15/618,666, filed on Jun. 9, 2017, granted, now 10,421,730, issued on Sep. 24, 2019.
Claims priority of provisional application 62/349,490, filed on Jun. 13, 2016.
Prior Publication US 2022/0204460 A1, Jun. 30, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 261/10 (2006.01); C07D 401/14 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); A61K 31/42 (2006.01); A61K 31/44 (2006.01); C07C 13/04 (2006.01); C07C 25/13 (2006.01); C07C 39/28 (2006.01); C07D 205/02 (2006.01)
CPC C07D 261/10 (2013.01) [A61K 31/42 (2013.01); A61K 31/44 (2013.01); C07C 13/04 (2013.01); C07C 25/13 (2013.01); C07C 39/28 (2013.01); C07D 205/02 (2013.01); C07D 401/14 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01)] 17 Claims
 
1. A method of treating a patient suffering from Primary Biliary Cirrhosis (PBC) or Primary Sclerosing Cholangitis (PSC) comprising administering to the patient a compound having the structure of Formula (Ia):

OG Complex Work Unit Chemistry
wherein:
Q is phenylene substituted with one chloro;
Y is N;
R1 is cyclopropyl or methyl;
R2 and R3 are chloro;
R4-A is:

OG Complex Work Unit Chemistry
wherein the pyridylene is optionally substituted with one or two groups independently selected from halogen, C1-4-alkoxy, halo-C1-4-alkoxy, C1-4-alkyl, and halo-C1-4-alkyl, and R4 is —CO2R5 or —C(O)NR5R6;
R5 is hydrogen; and
R6 is C1-2-alkyl optionally substituted with —CO2H or —SO3H;
or a pharmaceutically acceptable salt, a stereoisomer, a mixture of stereoisomers, or a tautomer thereof.