Malonyl-coenzyme A mimics as fatty acid synthase inhibitors and methods of use

Patent metadata

Field	Value
Publication number	US-11008362-B2
Application number	US-201916432147-A
Country	US
Kind code	B2
Filing date	Jun 5, 2019
Priority date	Jun 6, 2018
Publication date	May 18, 2021
Grant date	May 18, 2021

Abstract

The present disclosure generally relates to novel compounds as a fatty acid synthase inhibitor useful for the treatment of infection diseases, cancers, or metabolic diseases that malfunction of fatty acid synthase is involved. In particular this present invention directs to malonyl-coenzyme A (CoA) mimetics and methods of use thereof. The invention described herein also pertains to pharmaceutical compositions and methods for treating diseases in mammals using compounds disclosed herein.

First claim

What is claimed is:

1. A compound having a formula

or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein
X is co-enzyme A (CoA) or

Y is methylene (—CH 2 —), S, SO, NH, or O;
Z is N, S or SO; and
R 1 is hydrogen, an alkyl, alkenyl, or alkynyl.

2. The compound according to claim 1 , wherein R 1 is hydrogen, or a C 1 -C 24 alkyl.

3. The compound according to claim 2 , wherein R 1 is hydrogen.

4. The compound according to claim 2 , wherein R 1 is a C 1 -C 24 alkyl.

5. The compound according to claim 4 , wherein R 1 is methyl.

6. The compound according to claim 1 , wherein X is coenzyme A (CoA).

7. The compound according to claim 1 , wherein X is

8. The compound according to claim 1 , wherein said compound is

wherein R═S, O, NH; R′═SO, N + .

9. A pharmaceutical composition comprising one or more compounds of claim 1 , or a pharmaceutically acceptable salt thereof, together with one or more diluents, excipients or carriers.

10. A pharmaceutical composition comprising one or more compounds of claim 1 , or a pharmaceutically acceptable salt thereof, in combination with one or more other compounds of the same of different mode of action, together with one or more diluents, excipients or carriers.

Assignees

• Purdue Research Foundation

Inventors

• Lohman Jeremy R
• Stunkard Lee M

Classifications

• C07H19/207 Primary

  the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide · CPC title

• C07C237/22

  having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated (peptides C07K) · CPC title

• C07C327/30

  having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups · CPC title

• C07C309/21

  containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton · CPC title

• C07C309/17

  containing carboxyl groups bound to the carbon skeleton · CPC title