Substituted biaryl alkyl amides

Patent metadata

Field	Value
Publication number	US-10106491-B2
Application number	US-201615381535-A
Country	US
Kind code	B2
Filing date	Dec 16, 2016
Priority date	Oct 17, 2011
Publication date	Oct 23, 2018
Grant date	Oct 23, 2018

Abstract

Disclosed herein are substituted biaryl alkyl amide compounds, methods of synthesizing substituted biaryl alkyl amide compounds and methods of treating diseases and/or conditions with substituted biaryl alkyl amide compounds.

First claim

What is claimed is:

1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:

wherein:
n is selected from the group consisting of 0, 1, 2, 3, 4, and 5;
each R 1 is independently selected from the group consisting of halo, cyano, and azido;
Z 1 , Z 2 , Z 3 , and Z 4 are each independently —CH—;
R 2 is selected from the group consisting of an optionally substituted C 5-10 heteroaryl, and an optionally substituted C 3-7 heterocyclyl;
R 3 is —OH;
R 4 is

R 5 is hydrogen or —OH;
R 6 is selected from the group consisting of —OH, —NHR 7 , an optionally substituted C 1-6 alkyl, an optionally substituted C 1-6 alkoxy, an optionally substituted C 6-10 aryl, an optionally substituted C 5-10 heteroaryl, an optionally substituted aryloxy, and an optionally substituted arylalkoxy; and
R 7 is hydrogen or an optionally substituted C 1-6 alkyl.

2. The compound of claim 1 , wherein n is 2.

3. The compound of claim 1 , wherein each R 1 is halo.

4. The compound of claim 3 , wherein each R 1 is chloro.

5. The compound of claim 1 , wherein R 2 is selected from C 3-7 heterocyclyl.

6. The compound of claim 5 , wherein R 2 is selected from five or six membered heterocyclyl comprising one or two heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen.

7. The compound of claim 6 , wherein R 2 selected from optionally substituted tetrahydrofuranyl or optionally substituted pyrrolidinyl.

8. The compound of claim 1 , wherein R 5 is—OH.

9. The compound of claim 1 , wherein R 6 is selected from the group consisting of —OH, —NHR 7 , an optionally substituted C 1-6 alkyl, an optionally substituted C 1-6 alkoxy, and an optionally substituted arylalkoxy.

10. The compound of claim 9 , wherein R 6 is a substituted C 1-6 alkyl.

11. The compound of claim 10 , wherein the C 1-6 alkyl is substituted with one or more groups selected from the group consisting of halogen, —OH, —COOH, —NR 8 R 9 , C 1-6 alkoxy, and C 5-10 heteroaryl; wherein R 8 and R 9 are each independently hydrogen or C 1-6 alkyl.

12. The compound of claim 1 , wherein the compound of Formula (I) is selected from the group consisting of Formula (II), Formula (III), Formula (IV), Formula (V) and Formula (VI), or a pharmaceutically acceptable salt thereof:

wherein R 4 is selected from

13. The compound of claim 1 , wherein the compound of Formula (I) is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 12 , wherein the compound is enriched with respect to the shown stereochemistry in an amount that is >50% as compared to the amount of other stereoisomer impurities.

15. The compound of claim 12 , wherein the compound is enriched with respect to the shown stereochemistry in an amount that is >98% as compared to the amount of other stereoisomer impurities.

16. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient or combination thereof.

17. The pharmaceutical composition of claim 16 , wherein the compound is a mixture of two or more diastereomers.

Assignees

• Biotheryx Inc

Inventors

• Chan Kyle W H
• Mercurio Frank
• Stirling David I

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title