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:
-
99%, *data from raw suppliers
Lomitapide *data from reagent suppliers
Safty Information:
- Pictogram(s):
- Hazard Codes:
- MSDS Files:
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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
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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).
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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.
