title: Novel inhibitors of fatty acid oxidation as potential metabolic modulators.
abstract: We describe the synthesis of novel inhibitors of fatty acid oxidation as potential metabolic modulators for the treatment of stable angina. Replacement of the 2H-benzo[d]1,3-dioxolene ring system in our initial lead 3 with different benzthiazoles, benzoxazoles and introducing small alkyl substituents into the piperazine ring resulted in analogues with enhanced inhibitory activity against 1-(14)[C]-palmitoyl-CoA oxidation in isolated rat heart mitochondria (6, IC(50)=70 nM; 25, IC(50)=23 nM).
authors.affiliation: Department of Bioorganic Chemistry, CV Therapeutics Inc., 3172 Porter Drive, Palo Alto, CA 94304, USA. elfatih.elzein@cvt.com
authors.forename: Elfatih
authors.initials: E
authors.lastname: Elzein
authors.forename: Kevin
authors.initials: K
authors.lastname: Shenk
authors.forename: Prabha
authors.initials: P
authors.lastname: Ibrahim
authors.forename: Tim
authors.initials: T
authors.lastname: Marquart
authors.forename: Suresh
authors.initials: S
authors.lastname: Kerwar
authors.forename: Stephanie
authors.initials: S
authors.lastname: Meyer
authors.forename: Hiba
authors.initials: H
authors.lastname: Ahmed
authors.forename: Dewan
authors.initials: D
authors.lastname: Zeng
authors.forename: Nancy
authors.initials: N
authors.lastname: Chu
authors.forename: Daniel
authors.initials: D
authors.lastname: Soohoo
authors.forename: Shirley
authors.initials: S
authors.lastname: Wong
authors.forename: Kwan
authors.initials: K
authors.lastname: Leung
authors.forename: Jeff
authors.initials: J
authors.lastname: Zablocki
mesh_terms: D000818:Animals; D004852:Epoxy Compounds / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D010171:Palmitoyl Coenzyme A / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D004852:Epoxy Compounds; D005227:Fatty Acids; D010171:Palmitoyl Coenzyme A