title: Synthesis, X-ray crystal structure, and biological activity of FR186054, a novel, potent, orally active inhibitor of acyl-CoA:cholesterol O-acyltransferase (ACAT) bearing a pyrazole ring.
abstract: The synthesis, single crystal X-ray structural analysis, and biological activity of FR186054 (2c), a new, potent, orally efficacious inhibitor of acyl-CoA:cholesterol O-acyltransferase (ACAT), containing a pyrazole ring are described. This compound displayed excellent in vitro efficacy, irrespective of dosing method, indicating superior characteristics compared to other ACAT inhibitors.
authors.affiliation: Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Terasawa
authors.forename: H
authors.initials: H
authors.lastname: Hagihara
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Y
authors.initials: Y
authors.lastname: Sakuma
authors.forename: N
authors.initials: N
authors.lastname: Ishibe
authors.forename: M
authors.initials: M
authors.lastname: Sawada
authors.forename: H
authors.initials: H
authors.lastname: Takasugi
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D014508:Urea; C112873:FR 186054; D002785:Sterol O-Acyltransferase