Lomitapide Chemical Properties

Melting point:

142°C(lit.)

Boiling point:

778.2±60.0 °C(Predicted)

Density 

1.34±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO (Slightly), Methanol (Slightly)

pka

12.66±0.20(Predicted)

form 

powder

color 

white to beige

Safety Information

HS Code 

2933.39.4100

Hazardous Substances Data

182431-12-5(Hazardous Substances Data)

Lomitapide Usage And Synthesis

Description

Lomitapide was approved by the US FDA in December 2012 for the treatment of patients with familial hypercholesteremia (referred to as HoFH) in conjunction with a low-fat diet andother lipid-lowering treatments. Lomitapide was discovered from a high-through put screen that identified several structurally distinct MTP inhibitors. Combination of key structural features from two structurally distinct HTS hits provided potent MTP inhibitors. Parallel analog synthesis led to lomitapide as an optimized structure. Lomitapide was synthesized via alkylation of 9-fluorenylcarboxylic acid with 1,4-dibromobutane which, after trifluoroethylamide formation, provided a bromide intermediate that was displaced by Boc-4-aminopiperidine. Introduction of the 4'-trifluoromethylbiphenylcarboxamide gave lomitapide, which was found to inhibit MTP with an IC₅₀ of 0.5 nM and to exhibit good cholesterol-lowering efficacy in Sprague–Dawley rats (intravenous and oral ED₅₀～0.2 mg/kg).

Originator

Bristol-Myers Squibb (United States)

Uses

Lomitapide has been used as a microsomal triglyceride transfer protein (MTP) inhibitor to study its effects on very-low-density lipoproteins (VLDL) export in mouse hepatocytes.

Definition

ChEBI: Lomitapide is a member of the class of benzamides obtained by formal condensation of the carboxy group of 4'-(trifluoromethyl)biphenyl-2-carboxylic acid with the primary amino group of 9-[4-(4-aminopiperidin-1-yl)butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide. Used (as its mesylate salt) as a complement to a low-fat diet and other lipid-lowering treatments in patients with homozygous familial hypercholesterolemia. It has a role as an anticholesteremic drug and a MTP inhibitor. It is a member of piperidines, a member of fluorenes, a member of benzamides and a member of (trifluoromethyl)benzenes. It is a conjugate base of a lomitapide(1+).

brand name

Juxtapid

Biochem/physiol Actions

Lomitapide is an inhibitor of microsomal triglyceride transfer protein (MTP). Lomitapide has been shown to be highly effective in reducing LDL-cholesterol and triglycerides, and has been aproved for treatment of homozygous familial hypercholesterolemia.

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