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.
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.
Tanaka
A
A
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.
Terasawa
T
T
Hagihara
H
H
Kinoshita
T
T
Sakuma
Y
Y
Ishibe
N
N
Sawada
M
M
Takasugi
H
H
Tanaka
H
H
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
D004791:Enzyme Inhibitors; D011720:Pyrazoles; D014508:Urea; C112873:FR 186054; D002785:Sterol O-Acyltransferase