Delving into the Latest Updates on FR-182980 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

ACAT1

Mechanism

ACAT1 inhibitors(ACAT inhibitors)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Hypercholesterolemia

Originator Organization

Fujisawa Pharmaceutical Co., Ltd.

Active Organization-

Inactive Organization

Fujisawa Pharmaceutical Co., Ltd.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

Structure

Molecular FormulaC29H34FN3O2S2

InChIKeyVRCLMLMEOKXRHL-UHFFFAOYSA-N

CAS Registry179054-51-4

A series of N-alkyl-N-biphenylylmethyl-N'-arylurea and related derivatives represented by 1 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Linking of two phenyl groups via oxygen and introduction of fluorine at appropriate positions on the biphenyl moiety improved in vitro and in vivo activity. From this series of analogs, compound 40 (FR179254), which had potent in vitro potency (rabbit intestinal microsomes IC50 = 25 nM), showed excellent plasma cholesterol-lowering activity when administered via the diet (ED50 = 0.045 mg/kg). However, the hypocholesterolemic effect of this compound was moderate when dosed by oral gavage in PEG400 as a vehicle (ED50 = 5.3 mg/kg). Modification of the N'-aryl moiety led to the identification of compound 50 (FR182980) which was efficacious in both dosing models (ED50 = 0.034 mg/kg and 0.11 mg/kg, respectively).

100 Deals associated with FR-182980

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