Lomitapide

Base Information

• Chemical Name: Lomitapide
• CAS No.: 182431-12-5
• Deprecated CAS: 202833-31-6,210823-48-6
• Molecular Formula: C₃₉H₃₇F₆N₃O₂
• Molecular Weight: 693.732
• UNII: 82KUB0583F
• DSSTox Substance ID: DTXSID50171294
• Nikkaji Number: J1.390.273I
• Wikipedia: Lomitapide
• Wikidata: Q1268941
• NCI Thesaurus Code: C83891
• RXCUI: 1364479
• Pharos Ligand ID: Q46RVBT7USP3
• Metabolomics Workbench ID: 65918
• ChEMBL ID: CHEMBL354541
• Mol file: 182431-12-5.mol

Synonyms:AEGR 733;AEGR-733;AEGR733;BMS 201038;BMS-201038;BMS201038;Juxtapid;lomitapide

Chemical Property of Lomitapide

Chemical Property:

• Melting Point: 142°C(lit.)
• Boiling Point: 778.2±60.0 °C(Predicted)
• PKA: 12.66±0.20(Predicted)
• PSA: 68.42000
• Density: 1.34±0.1 g/cm3(Predicted)
• LogP: 9.73510
• Storage Temp.: 2-8°C
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 8.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 10
• Exact Mass: 693.27899640
• Heavy Atom Count: 50
• Complexity: 1110

Purity/Quality:

98%,99%, ^*data from raw suppliers

Lomitapide ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antilipemic Agents
• Canonical SMILES: C1CN(CCC1NC(=O)C2=CC=CC=C2C3=CC=C(C=C3)C(F)(F)F)CCCCC4(C5=CC=CC=C5C6=CC=CC=C64)C(=O)NCC(F)(F)F
• Recent ClinicalTrials: Efficacy and Safety of Lomitapide in Paediatric Patients With Homozygous Familial Hypercholesterolaemia (HoFH)
• Recent EU Clinical Trials: Phase III, single-arm, open-label, international, multi-centre study to evaluate the efficacy and safety of lomitapide in paediatric patients with Homozygous Familial Hypercholesterolaemia (HoFH) on stable lipid-lowering therapy
• 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).
• 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.

Technology Process of Lomitapide

There total 29 articles about Lomitapide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 70.0%

N-(1-piperidin-4-yl)-4'-(trifluoromethyl)-[1,1'-biphenyl]-2-carboxamide hydrochloride + 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid-(2,2,2-trifluoro-ethyl)-amide (182438-98-8) → 9-[4-[4-[[[4'-(trifluoromethyl)[1,1'-biphenyl]-2-yl]carbonyl]amino]-1-piperidinyl]butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide (182431-12-5)

Guidance literature:

With triethylamine; In acetonitrile; at 50 ℃; for 6h;

Reference yield:

N-(1-piperidin-4-yl)-4'-(trifluoromethyl)-[1,1'-biphenyl]-2-carboxamide (182439-41-4) + 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid-(2,2,2-trifluoro-ethyl)-amide (182438-98-8) → 9-[4-[4-[[[4'-(trifluoromethyl)[1,1'-biphenyl]-2-yl]carbonyl]amino]-1-piperidinyl]butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide (182431-12-5)

Guidance literature:

With potassium carbonate; sodium iodide; In N,N-dimethyl-formamide; at 25 - 30 ℃;

Reference yield:

9-{4-[4-({[4'-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)piperidin-1-yl]butyl}-9H-fluorene-9-carboxylic acid + 2,2,2-trifluroethylamine hydrochloride (373-88-6) → 9-[4-[4-[[[4'-(trifluoromethyl)[1,1'-biphenyl]-2-yl]carbonyl]amino]-1-piperidinyl]butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide (182431-12-5)

Guidance literature:

9-{4-[4-({[4'-(trifluoromethyl)biphenyl-2-yl]carbonyl}amino)piperidin-1-yl]butyl}-9H-fluorene-9-carboxylic acid; With chloroformic acid ethyl ester; triethylamine; In dichloromethane; at 0 ℃; for 1.75h;

2,2,2-trifluroethylamine hydrochloride; With sodium hydroxide; In dichloromethane; at 0 - 20 ℃; for 1.5h;

upstream raw materials:

2,2,2-trifluroethylamine hydrochloride

9H-fluorene-9-carboxylic acid

methyl 9H-fluorene-9-carboxylate

N-(1-benzylpiperidin-4-yl)-4'-(trifluoromethyl)-[1,1'-biphenyl]-2-carboxamide

Refernces

• 1、 -. "PROCESS FOR MAKING LOMITAPIDE MESYLATE". . . Retrieved 2016/02/18.
• 2、 -. "PROCESS FOR THE PREPARATION OF LOMITAPIDE". . . Retrieved 2016/06/01.