Compositions and methods for modulating farnesoid x receptors

A compound, technology of alkyl, applied in the field of composition for regulating farnesoid X receptor

Active Publication Date: 2016-06-15
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although progress has been made in the development of new FXR agonists, there is still huge room for improvement

Method used

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  • Compositions and methods for modulating farnesoid x receptors
  • Compositions and methods for modulating farnesoid x receptors
  • Compositions and methods for modulating farnesoid x receptors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach 1

[0246] Embodiment 1. A compound of formula (I) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof,

[0247]

[0248] in:

[0249] R 0 for Ring A or C 1-6 Alkyl; where

[0250] Ring A is an aryl group; a 5-10 membered heteroaryl group containing 1-3 N, O or S heteroatoms; a 4-6 membered heterocycle containing 1-2 N, O or S heteroatoms; or C 3-7 Cycloalkyl; each of them is unsubstituted or replaced by 1-2 each represented by R 2 Substituents independently represented by substituents; where L 3 and R 0 Can be attached to the same and different ring atoms of ring A; C 1-6 Alkyl is optionally replaced by 1-2 C 1-6 Alkyl substitution;

[0251] Ring B is aryl; 5-10 membered heteroaryl containing 1-3 N, O or S heteroatoms; 4-6 membered heterocyclic ring containing 1-2 N, O or S heteroatoms; or C 3-7 Cycloalkyl; each of them is unsubstituted or replaced by 1-2 each represented by R 2 substituent substitution by independent representatives;

[0252] ...

Embodiment approach 2

[0261] Embodiment 2. The compound of Embodiment 1, or a salt, tautomer or stereoisomer thereof, wherein said compound is represented by formula (II),

[0262]

[0263] in:

[0264] R 0 for Ring A or C 1-6 Alkyl; where:

[0265] Ring A is selected from phenyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl and C 3-7 Cycloalkyl, each of which is unsubstituted or replaced by 1 to 3 each represented by R 2 Substituents independently represented by substituents; where L 3 and R 0 Can be attached to the same and different ring atoms of ring A; C 1-6 Alkyl is optionally replaced by 1-2 C 1-6 Alkyl substitution;

[0266] Ring B is selected from phenyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1H-indolyl and C 3-7 Cycloalkyl, each of which is unsubstituted or replaced by 1-2 each represented by R 2 substituent substitution by independent representatives;

[0267] X is (CR 4 R 5 );

[0268] Y is O, (CR 4 R 5 ) or *O(CR 4 R 5 ), where "*" indicates the point of at...

Embodiment approach 3

[0275] Embodiment 3. The compound of Embodiment 1 or 2, or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R 0 selected from* 3 -CH 2 C(CH 3 ) 2 -,* 3 -CH 2 CH(CH 3 )-and* 3 -cyclopropane-1,1-diyl-, where "* 3 " means R 0 with L 2 connection point.

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Abstract

The present invention relates to compounds of Formula I, a stereoisomer, enantiomer, a pharmaceutically acceptable salt or an amino acid conjugate thereof; wherein variables are as defined herein; and their pharmaceutical compositions, which are useful as modulators of the activity of Farnesoid X receptors (FXR).

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 61 / 900,013, filed November 5, 2013, the entire contents of which are incorporated herein by reference. technical field [0003] The present invention relates to compositions and methods for modulating farnesoid X receptors (FXRs). Background technique [0004] The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily and is mainly expressed in the liver, kidney and intestine (see, e.g., Seol et al., (1995) Mol. Endocrinol. 9:72-85 and Forman et al., (1995) Cell 81:687-693). As a heterodimer with the retinol X receptor (RXR), it binds to response elements in the promoters of target genes to regulate gene transcription. The FXR-RXR heterodimer binds with the highest affinity to the inverted repeat-1 (IR-1) response element, where consensus receptor-binding hexamers are separated by one nucleotide. FXR is part of this...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4162C07D471/04C07D491/052
CPCC07D471/04C07D491/052A61K31/416A61K31/4162A61K31/4439A61K31/4745C07D231/54C07D471/06A61P1/00A61P1/04A61P1/08A61P1/12A61P1/16A61P1/18A61P43/00A61K45/06A61K2300/00
Inventor D·基亚内利刘晓东V·莫尔泰尼J·内尔森J·罗兰P·鲁克尔D·图利
Owner NOVARTIS AG
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