US 11,912,674 B2
Isoxazole derivatives as nuclear receptor agonists and uses thereof
Jae-Hoon Kang, Seoul (KR); Hong-Sub Lee, Youngin-si (KR); Yoon-Suk Lee, Hwaseong-si (KR); Jin-Ah Jeong, Seoul (KR); Sung-Wook Kwon, Hwaseong-si (KR); Jeong-Guen Kim, Hwaseong-si (KR); Kyung-Sun Kim, Gunpo-si (KR); Dong-Keun Song, Seoul (KR); Sun-Young Park, Hwaseong-si (KR); Kyeo-Jin Kim, Seoul (KR); Ji-Hye Choi, Hwaseong-si (KR); and Hey-Min Hwang, Seoul (KR)
Assigned to IL DONG PHARMACEUTICAL CO., LTD., Seoul (KR)
Filed by ILDONG Pharmaceutical Co., Ltd., Seoul (KR)
Filed on Mar. 4, 2021, as Appl. No. 17/191,806.
Application 17/191,806 is a continuation of application No. 16/604,180, granted, now 10,988,449, previously published as PCT/KR2018/004277, filed on Apr. 12, 2018.
Claims priority of application No. 10-2017-0047393 (KR), filed on Apr. 12, 2017; and application No. 10-2018-0042545 (KR), filed on Apr. 12, 2018.
Prior Publication US 2021/0188790 A1, Jun. 24, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 261/08 (2006.01)
CPC C07D 261/08 (2013.01) 13 Claims
 
1. A method for treating or ameliorating metabolic diseases, cholestatic liver diseases, or organ fibrosis, the method comprising:
administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising (i) a compound represented by Formula I, a racemate, an enantiomer, or a diastereoisomer thereof, or a pharmaceutically acceptable salt of the compound, the racemate, the enantiomer, or the diastereoisomer and (ii) a carrier,

OG Complex Work Unit Chemistry
wherein:
R1 and R2 are each independently hydrogen, halo, or trifluoromethyl;
R6 and R7 are each independently hydrogen, halo, trifluoromethyl, or trifluoromethoxy;
Y is carbon or nitrogen; and
Z is

OG Complex Work Unit Chemistry
wherein:
n is 0, 1, or 2;
X1, X2, and X3 are each independently carbon or nitrogen;
Rc3 is hydrogen, halo, C1-6 alkyl, or C3-6 cycloalkyl;
W1, W2, and W3 are each independently oxygen, nitrogen, CHRw1, CRw1, NRw1, or CO, wherein Rw1 is hydrogen, halo, C1-6 alkyl, C3-6 cycloalkyl, halo C1-6 alkyl, C1-6 alkylamine, C1-6 alkyl alcohol,

OG Complex Work Unit Chemistry
 (CH2)p heteroaryl, or (CH2)p aryl, wherein, p is 1, 2, or 3;
R5 is hydrogen

OG Complex Work Unit Chemistry
 and
R3 and R4 are each independently hydrogen, halo, cyano, C1-6 alkyl, C3-6 cycloalkyl, halo C1-6 alkyl,

OG Complex Work Unit Chemistry
 CONRa1Ra2, NRa1Ra2 CH2NRa1Ra2, CH2Rc3, CORa3, ORa3, NRa4CORa3, NRa4CO2Ra3, NHCONHRa3, NHSO2Ra3, or 3- or 8-membered heterocycles containing one or two oxygen or nitrogen atom(s) therein,
wherein:
m is 1 or 2;
Ra1 and Ra2 are each independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, halo C1-6 alkyl,

OG Complex Work Unit Chemistry
 or 3- or 8-membered heterocycles containing one or two oxygen or nitrogen atom(s) therein;
Ra3 is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, halo C1-6 alkyl,

OG Complex Work Unit Chemistry
 or 3- or 8-membered heterocycles containing one or two oxygen or nitrogen atom(s) therein; and
Ra4 is hydrogen or C1-6 alkyl.