3-Aryl-4-hydroxyquinolin-2(1H)-one derivatives as type I fatty acid synthase inhibitors

Alexey Rivkin; Yoona R Kim; Mark T Goulet; Nathan Bays; Armetta D Hill; Ilona Kariv; Stefan Krauss; Nicole Ginanni; Peter R Strack; Nancy E Kohl; Christine C Chung; Jeffrey P Varnerin; Paul N Goudreau; Amy Chang; Michael R Tota; Benito Munoz

doi:10.1016/j.bmcl.2006.06.014

3-Aryl-4-hydroxyquinolin-2(1H)-one derivatives as type I fatty acid synthase inhibitors

Bioorg Med Chem Lett. 2006 Sep 1;16(17):4620-3. doi: 10.1016/j.bmcl.2006.06.014. Epub 2006 Jun 19.

Authors

Alexey Rivkin¹, Yoona R Kim, Mark T Goulet, Nathan Bays, Armetta D Hill, Ilona Kariv, Stefan Krauss, Nicole Ginanni, Peter R Strack, Nancy E Kohl, Christine C Chung, Jeffrey P Varnerin, Paul N Goudreau, Amy Chang, Michael R Tota, Benito Munoz

Affiliation

¹ Department of Chemistry, Merck Research Laboratories, Boston, MA 02115, USA. alexey_rivkin@merck.com

PMID: 16784844
DOI: 10.1016/j.bmcl.2006.06.014

Abstract

A series of 3-aryl-4-hydroxyquinolin-2(1H)-ones with fatty acid synthase inhibitory activity was prepared. Starting from a derivative with an IC(50) = 1.4 microM, SAR studies led to compounds with more than 70-fold increase in potency (IC(50) < 20 nM).

MeSH terms

Animals
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Fatty Acid Synthases / antagonists & inhibitors*
Fatty Acid Synthases / metabolism
Humans
Hydroxyquinolines / chemical synthesis
Hydroxyquinolines / chemistry*
Hydroxyquinolines / pharmacology*
Malonates / chemistry
Microwaves
Molecular Structure
Quinolines / chemical synthesis
Quinolines / chemistry*
Quinolines / pharmacology*
Rats
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Hydroxyquinolines
Malonates
Quinolines
Fatty Acid Synthases