182431-12-5

Basic information

• Product Name: N-(2,2,2-Trifluoroethyl)-9-(4-[4-[4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxamido]piperidin-1-yl]butyl)-9H-fluorene-9-carboxamide
• Synonyms: N-(2,2,2-Trifluoroethyl)-9-(4-[4-[4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxamido]piperidin-1-yl]butyl)-9H-fluorene-9-carboxamide;AEGR 733;BMS 201038;BMS 201038-01;BMS 201238;LoMitapide;N-(2,2,2-trifluoroethyl)-9-(4-(4-(4'-(trifluoroMethyl)biphenyl-2-ylcarboxaMido)piperidin-1-yl)butyl)-9H-fluorene-9-carboxaMide;CB62485047,loMitapide
• CAS NO: 182431-12-5
• Molecular Formula: C39H37F6N3O2
• Molecular Weight: 693.7203992
• Product Categories: Inhibitors
• Mol File: 182431-12-5.mol
• Article Data: 9

Chemical Properties

• Melting Point: 142°C(lit.)
• Boiling Point: 778.2±60.0 °C(Predicted)
• Appearance: /
• Density: 1.34±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 12.66±0.20(Predicted)
• CAS DataBase Reference: N-(2,2,2-Trifluoroethyl)-9-(4-[4-[4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxamido]piperidin-1-yl]butyl)-9H-fluorene-9-carboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(2,2,2-Trifluoroethyl)-9-(4-[4-[4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxamido]piperidin-1-yl]butyl)-9H-fluorene-9-carboxamide(182431-12-5)
• EPA Substance Registry System: N-(2,2,2-Trifluoroethyl)-9-(4-[4-[4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxamido]piperidin-1-yl]butyl)-9H-fluorene-9-carboxamide(182431-12-5)

Safety Data

• Hazardous Substances Data: 182431-12-5(Hazardous Substances Data)

Usage

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.

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.

Upstream product

• 373-88-6 2,2,2-trifluroethylamine hydrochloride 
• 1989-33-9 9H-fluorene-9-carboxylic acid 
• 3002-30-0 methyl 9H-fluorene-9-carboxylate 
• 182439-40-3 N-(1-benzylpiperidin-4-yl)-4'-(trifluoromethyl)-[1,1'-biphenyl]-2-carboxamide 
• 84392-17-6 4'-(trifluoromethyl)-2-biphenylcarboxylic acid 
• 50541-93-0 4-amino-1-benzylpiperidine 
• 182439-41-4 N-(1-piperidin-4-yl)-4'-(trifluoromethyl)-[1,1'-biphenyl]-2-carboxamide 
• 182438-98-8 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid-(2,2,2-trifluoro-ethyl)-amide 
• 88-67-5 2-Iodobenzoic acid 
• 128796-39-4 4-trifluoromethylphenylboronic acid 
• 182438-97-7 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid 
• 331767-53-4 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid chloride 
• 87120-72-7 1-(tert-butoxycarbonyl)-4-aminopiperidine 

Relevant articles and documents

CRYSTALLINE POLYMORPH OF N-(2,2,2-TRIFLUOROETHYL-9-[4-[R4-R[[[I4'- (TRIFLUOROMETHYL) [ 1,1 ' -BIPHENYL] -2-YL] CARBONYL] AMINO] -1 -PIPERIDINYL] BUTYL] -9H- FLUORENE-9-CARBOXAMIDE METHANESULFONATE AND PROCESS FOR PREPARATION THEREOF

The present invention relates to? crystalline polymorph of N-(2,2.2-trifluoroethyl)-9- [4- [4- [ [[4,-(trifluoromethyl) [1,1 '-biphenyl] -2-yl] carbonyl] amino] - 1 -piperidinyl] butyl] -9H- fluorene-9-carboxamide methanesulfonate salt represented by the following structural formula- la and process for preparation thereof.

AMORPHOUS FORM OF LOMITAPIDE MESYLATE

Provided is novel amorphous form of lomitapide mesylate salt and process for preparation thereof.

Method for synthesizing triglyceride transfer protease inhibitor

The invention discloses a method for synthesizing the triglyceride transfer protease inhibitor Lomitapide. Specifically, based on improvement of an existing technique, the compounds 9-carboxyfluorene and 1,4-dibromobutane are used as raw materials, five-step reaction is conducted, and the defects of the prior art are overcome. Compared with the prior art, the method has the main advantage that column chromatography purification is avoided, and product purification is conducted with a recrystallization method which is economical and environment-friendly.