2-piperidinyl substituted N,3-dihydroxybutanamides

Patent metadata

Field	Value
Publication number	US-9908851-B2
Application number	US-201414912137-A
Country	US
Kind code	B2
Filing date	Aug 18, 2014
Priority date	Aug 16, 2013
Publication date	Mar 6, 2018
Grant date	Mar 6, 2018

Abstract

Disclosed are compounds of formulae: (I) and pharmaceutically acceptable salts thereof, wherein the variables, R 1 , R 2 , Y, and Z are defined herein. These compounds are useful for treating Gram-negative bacteria infections.

First claim

What is claimed is:

1. A compound that is:

or pharmaceutically acceptable salts thereof.

2. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, solvent, adjuvant or diluent.

3. A method of treating Gram-negative bacterial infections, the method comprising administering to a subject in need of such treatment an effective amount of one or more compounds according to claim 1 .

4. A method of inhibiting a deacetylase enzyme in Gram-negative bacteria, the method comprising administering to a subject in need of such treatment an effective amount of one or more compounds according to claim 1 .

5. A compound of formula:

or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen; and
R 2 is

6. A compound according to claim 5 , wherein the compound is of formula:

7. A compound according to claim 5 , wherein R 2 represents

8. A compound according to claim 5 , wherein R 2 represents

9. A compound according to claim 5 that is:

or pharmaceutically acceptable salts thereof.

10. A pharmaceutical composition comprising a compound according to claim 5 and a pharmaceutically acceptable carrier, solvent, adjuvant or diluent.

11. A method of treating Gram-negative bacterial infections, the method comprising administering to a subject in need of such treatment an effective amount of one or more compounds according to claim 5 .

12. A method of inhibiting a deacetylase enzyme in Gram-negative bacteria, the method comprising administering to a subject in need of such treatment an effective amount of one or more compounds according to claim 5 .

13. A compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein
Y represents phenyl optionally substituted with R 4 ;
Z represents phenyl optionally substituted with R 5 ;
R 1 is hydrogen;
R 2 is

each R 4 is independently selected from the group consisting of halogen, —NO 2 , —CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —NH 2 , —NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl) 2 , —OH, C 1 -C 6 alkoxy, and C 1 -C 6 haloalkoxy; and
each R 5 is independently selected from the group consisting of halogen, —NO 2 , —CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —NH 2 , —NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl) 2 , —OH, C 1 -C 6 alkoxy, and C 1 -C 6 haloalkoxy.

14. A compound according to claim 13 , wherein R 2 represents

15. A pharmaceutical composition comprising a compound according to claim 13 and a pharmaceutically acceptable carrier, solvent, adjuvant or diluent.

16. A method of treating Gram-negative bacterial infections, the method comprising administering to a subject in need of such treatment an effective amount of one or more compounds according to claim 13 .

17. A method of inhibiting a deacetylase enzyme in Gram-negative bacteria, the method comprising administering to a subject in need of such treatment an effective amount of one or more compounds according to claim 13 .

Assignees

• Univ Duke
• Univ Of North Carolina Chapel Hill

Inventors

• Zhou Pei
• Toone Eric J
• Nicholas Robert A

Classifications

• A61K31/455

  Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides · CPC title

• C07D211/06 Primary

  having no double bonds between ring members or between ring members and non-ring members · CPC title

• C07D211/14

  with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title