1,4,5-substituted 1,2,3-triazole analogues as antagonists of the pregnane X receptor

Patent metadata

Field	Value
Publication number	US-10947203-B2
Application number	US-201916679007-A
Country	US
Kind code	B2
Filing date	Nov 8, 2019
Priority date	Mar 25, 2016
Publication date	Mar 16, 2021
Grant date	Mar 16, 2021

Abstract

In an aspect, the invention relates to 1,4,5-substituted 1,2,3-triazole and 1,2,4,5-substituted imidazoles having a structure represented by a formula:

which are modulators the pregnane X receptor (“PXR”); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of modulating an adverse drug reaction in a mammal using the compounds and pharmaceutical compositions; methods of treatment of a disorder of uncontrolled cellular proliferation, such as a cancer, using the compounds and pharmaceutical compositions; methods of modulating pregnane X receptor activity in a mammal using the compounds and pharmaceutical compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

First claim

What is claimed is:

1. A pharmaceutical composition comprising a therapeutically effective amount of a compound having a structure represented by a formula:

wherein R 1 is hydroxy, halogen, C1-C6 alkyl, C1-C6 alkoxy, or (C1-C6)OH;
wherein R 2 is hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 monohaloalkyl, C1-C6 polyhaloalkyl, —CO 2 H, —(C═O)H, —(C═O)-(C1-C6 alkyl), or (C═O)—O(C1-C6 alkyl);
wherein R 3 is hydrogen, hydroxy, halogen, C1-C6 alkyl, C1-C6 alkoxy, or -(C1-C6)-OH;
wherein R 5 is hydrogen, halogen, hydroxy, or C1-C3 alkyl;
wherein R 6 is hydrogen, halogen, hydroxy, or C1-C3 alkyl; and
wherein R 7 is C1-C6 alkyl,
or a pharmaceutically acceptable salt thereof, provided that the compound is not:

and a pharmaceutically acceptable carrier.

2. The composition of claim 1 , wherein R 1 is alkoxy and R 3 is alkoxy.

3. The composition of claim 1 , wherein R 3 is methoxy.

4. The composition of claim 1 , wherein R 7 is tert-butyl.

5. The composition of claim 1 , wherein R 1 is hydroxy, halogen, methyl, ethyl, methoxy, or ethoxy; wherein R 2 is fluoro or methyl; wherein R 3 is hydroxy, halogen, methyl, ethyl, methoxy, or ethoxy; wherein R 5 is hydrogen, hydroxy, or methyl; wherein R 6 is hydrogen, hydroxy, or methyl; and wherein R 7 is propyl, isopropyl, n-butyl, tert-butyl, or sec-butyl.

6. The composition of claim 1 , wherein the compound has a structure represented by formula:

7. The composition of claim 1 , wherein the compound has a structure:

8. The composition of claim 1 , wherein the compound has a structure:

9. The composition of claim 1 , wherein the compound is:

10. The composition of claim 1 , wherein the compound is:

Assignees

• St Jude Childrens Res Hospital
• St Jude Childrens Rsearch Hospital

Inventors

• Chen Taosheng
• Lin Wenwei
• Wang Yueming

Classifications

• A61K9/205

  Polysaccharides, e.g. alginate, gums; Cyclodextrin · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61K9/0095

  Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006) · CPC title