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

A Tanaka; T Terasawa; H Hagihara; T Kinoshita; Y Sakuma; N Ishibe; M Sawada; H Takasugi; H Tanaka

doi:10.1016/s0960-894x(97)10191-3

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

Bioorg Med Chem Lett. 1998 Jan 6;8(1):81-6. doi: 10.1016/s0960-894x(97)10191-3.

Authors

A Tanaka¹, T Terasawa, H Hagihara, T Kinoshita, Y Sakuma, N Ishibe, M Sawada, H Takasugi, H Tanaka

Affiliation

¹ Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.

PMID: 9871633
DOI: 10.1016/s0960-894x(97)10191-3

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.

MeSH terms

Administration, Oral
Animals
Biological Availability
Crystallography, X-Ray
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Molecular Structure
Pyrazoles / chemical synthesis*
Pyrazoles / chemistry*
Pyrazoles / pharmacology
Rabbits
Rats
Sterol O-Acyltransferase / antagonists & inhibitors*
Urea / analogs & derivatives*
Urea / chemical synthesis
Urea / chemistry
Urea / pharmacology

Substances

Enzyme Inhibitors
Pyrazoles
Urea
FR 186054
Sterol O-Acyltransferase