Hormone receptor modulators for treating metabolic conditions and disorders
Inventors
Chao, Jianhua • Jain, Rakesh • Hu, Lily • Lewis, Jason Gustaf • Baribault, Helene • Caldwell, Jeremy
Assignees
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Publication Number
US-10793568-B2
Publication Date
2020-10-06
Expiration Date
Abstract
The invention relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): (I), wherein L1, A, X1, X2, R1, R2, and R3 are described herein.
Core Innovation
The invention relates to compounds of Formula (Ix), or a salt thereof, with defined structural elements including L1, ring system A, substituents R1, R2, R3, R4, and R6a. Formula (Ix) is an explicit example structure within a broader family of Formula (I) chemical structures, with A as phenyl, R1 and R2 both Cl, R3 as cyclopropyl, R4 as COOR6a, R6a as H, and L1 as —(CH2)p— where p is 1.
The disclosure provides stereospecific azabicycloheptane oxazole-containing compounds and related bicyclic aryl compounds, including numerous labeled examples and analogs. It reports preparation and characterization of multiple intermediates and final compounds, with structural variations on aromatic carboxylate, heteroaryl, benzothiazole, benzoic acid, benzamide, sulfonamide, and oxazole-containing scaffolds.
The document further includes analytical characterization data for disclosed members, including 1H NMR and MS/[M+1], together with structures, yields, and purification references for selected compounds. The disclosed compounds are described as FXR modulators, particularly FXR activators or agonists.
Claims Coverage
The independent claim coverage is centered on one compound class: Formula (Ix), or a salt thereof. The claim includes six fixed inventive features: L1 as —(CH2)p— with p=1, A as phenyl, R1 and R2 both Cl, R3 as cyclopropyl, R4 as COOR6a, and R6a as H.
Compound of Formula (Ix) or salt thereof
A compound of Formula (Ix), or a salt thereof.
L1 defined as —(CH2)p— with p=1
L1 is —(CH2)p— and p is 1.
A is phenyl
A is phenyl.
R1 and R2 are both Cl
R1 and R2 are both Cl.
R3 is cyclopropyl
R3 is cyclopropyl.
R4 is COOR6a and R6a is H
R4 is COOR6a and R6a is H.
Claim clm-00001 is limited to a Formula (Ix) compound, or a salt thereof, with fixed structural selections: phenyl for A, chloride for both R1 and R2, cyclopropyl for R3, COOR6a for R4 with R6a as H, and L1 defined as —(CH2)p— with p=1.
Stated Advantages
FXR modulators, particularly FXR activators/agonists.
Anti-inflammatory activity is described in connection with FXR-related biological regulation.
Documented Applications
Methods of using the compounds to modulate or activate FXR.
Treatment of diseases or disorders where FXR plays a role, including liver, intestinal, kidney, autoimmune disorders, and cancer.
In vivo use in DSS-induced colitis and a HFCC diet colonic permeability model.
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