Lecimibide

Structural formula
General
Non-proprietary name	Lecimibide
other names	3- (2,4-Difluorophenyl) -1- [5 - [(4,5-diphenylimidazol-2-yl) thio] pentyl] -1-heptylurea ( IUPAC ) N '- (2,4-difluorophenyl) - N - (5 - ((4,5-diphenyl-1 H -imidazol-2-yl) thio) pentyl) - N -heptylharnstoff DuP 128
Molecular formula	C 34 H 40 F 2 N 4 OS
External identifiers / databases
CAS number 130804-35-2 PubChem 71355 Wikidata Q1303494
Drug information
Mechanism of action	Acyl-CoA: cholesterol- O- acyltransferase inhibitor
properties
Molar mass	590.77 g · mol -1
safety instructions
GHS hazard labeling no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Lecimibide is a fluorine- containing chemical compound from the group of imidazoles . The drug lecimibide selectively inhibits acyl-CoA: cholesterol-O-acyltransferase, ACAT for short , with an IC ₅₀ value of 10 nM, measured on microsomes from rat liver, in a strong, non-competitive manner . The main function of this enzyme is the esterification of cholesterol in the context of intracellular cholesterol homeostasis and cholesterol absorption from the intestinal lumen ( inside the intestine ).

properties

Lecimibide is poorly absorbed by the body. An initial phase I study in 1994 showed only a minor effect on the inhibition of cholesterol absorption. This triggered the further search for ACAT inhibitors with higher bioavailability.

While lecimibide has no effect on the ACAT homologues in the yeast Saccharomyces cerevisiae , it inhibits human ACAT in vitro .

use

Lecimibide is currently in studies aimed at drug development as a cholesterol lowering agent.

proof

For the detection of Lecimibid and its sulphone - and sulphoxide - metabolites in human plasma by CM Lai was et al. an HPLC method with fluorescence detection is described.

literature

• Yang, Hongyuan et al .: Functional Expression of a cDNA to Human Acyl-coenzyme A: Cholesterol Acyltransferase in Yeast J. Biol. Chem. 1997 Feb 14; 272 (7): 3980-3985, PMID 9020103 .
• King, FD and Oxford, AW: Progress in Medicinal Chemistry: Vol 39 Elsevier, 2002 ISBN 0-444-50959-3

Pharmacology:

• Burnett, JR et al. : Inhibition of cholesterol esterification by DuP 128 decreases hepatic apolipoprotein B secretion in vivo: effect of dietary fat and cholesterol. Biochim Biophys Acta . 1998 Jul 31; 1393 (1): 63-79, PMID 9714740 .
• Whitman, SC et al. : Modification of Type III VLDL, Their Remnants, and VLDL From ApoE-Knockout Mice by p-Hydroxyphenylacetaldehyde, a Product of Myeloperoxidase Activity, Causes Marked Cholesteryl Ester Accumulation in Macrophages Arterioscler Thromb Vasc Biol. 1999 May; 19 (5): 1238– 1249, PMID 10323775 .

Synthesis and analytics:

• Highley, CA et al. : Acyl CoA: cholesterol acyltransferase (ACAT) inhibitors: synthesis and structure-activity relationship studies of a new series of trisubstituted imidazoles J. Med. Chem. 1994 Oct 14; 37 (21): 3511-3522, PMID 7932580 .

Individual evidence

1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
2. ↑ Hainer, JW et al. : Effect of the acyl-CoA: cholesterol acyltransferase inhibitor DuP 128 on cholesterol absorption and serum cholesterol in humans Clin Pharmacol Ther . 1994 Jul; 56 (1): 65-74, PMID 8033496 .
3. ↑ Database research of the DIMDI / Medline database DIMDI .
4. ↑ Lai, Chii-Ming Determination of DuP 128, an ACAT inhibitor and its sulphoxide and sulphone metabolites in human plasma by liquid chromatography J. Pharm. Biomed. Anal. 1994 Sep; 12 (9): 1163-1172, PMID 7803568 .
5. ^ FD King: Progress in Medicinal Chemistry. Elsevier, 2002, ISBN 9780444509598 , p. 144. Restricted preview in Google Book Search.

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