title: CVT-4325: a potent fatty acid oxidation inhibitor with favorable oral bioavailability.
abstract: New inhibitors of palmitoyl-CoA oxidation are based on the introduction of nitrogen heterocycles in the 'Western Portion' of the molecule. SAR studies led to the discovery of CVT-4325 (shown), a potent FOXi (IC50=380 nM rat mitochondria) with favorable PK properties (F=93%, t(1/2)=13.6h, dog).
authors.affiliation: Department of Bioorganic Chemistry, CV Therapeutics, Inc., 3172 Porter Dr., Palo Alto, CA 94304, USA.
authors.forename: Elfatih
authors.initials: E
authors.lastname: Elzein
authors.forename: Prabha
authors.initials: P
authors.lastname: Ibrahim
authors.forename: Dmitry O
authors.initials: DO
authors.lastname: Koltun
authors.forename: Ken
authors.initials: K
authors.lastname: Rehder
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Shenk
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Marquart
authors.forename: Bob
authors.initials: B
authors.lastname: Jiang
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Li
authors.forename: Reina
authors.initials: R
authors.lastname: Natero
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Marie
authors.initials: M
authors.lastname: Nguyen
authors.forename: Suresh
authors.initials: S
authors.lastname: Kerwar
authors.forename: Nancy
authors.initials: N
authors.lastname: Chu
authors.forename: Daniel
authors.initials: D
authors.lastname: Soohoo
authors.forename: Jia
authors.initials: J
authors.lastname: Hao
authors.forename: Victoria Y
authors.initials: VY
authors.lastname: Maydanik
authors.forename: David A
authors.initials: DA
authors.lastname: Lustig
authors.forename: Dewan
authors.initials: D
authors.lastname: Zeng
authors.forename: Kwan
authors.initials: K
authors.lastname: Leung
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Zablocki
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D004285:Dogs; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008968:Molecular Conformation; D010069:Oxadiazoles / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010171:Palmitoyl Coenzyme A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D005227:Fatty Acids; D010069:Oxadiazoles; C499690:para-trifluoro-methyl-5-phenyl-1,2,4-oxadiazole; D010171:Palmitoyl Coenzyme A