Cipralisant
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| Non-proprietary name | Cipralisant | |||||||||
| other names |
(1 S , 2 S ) -4- [2- (5,5-Dimethylhex-1-ynyl) -cyclopropyl] imidazole |
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| Molecular formula | C 14 H 20 N 2 | |||||||||
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| Mechanism of action |
Selective histamine H 3 ligand |
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| Molar mass | 216.32 g · mol -1 | |||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||
Cipralisant ( GT-2331 ) is a by the company Gliatech developed drug from the group of H 3 antihistamines . This substance was one of the first clinically investigated H 3 antihistamines and was tested in phase II studies for the treatment of attention deficit / hyperactivity disorder in the early 2000s. However, there was no further clinical investigation and approval for the therapy after MSD Sharp & Dohme took over Gliatech .
pharmacology
Although cipralisant was originally identified as an antagonist at the histamine H 3 receptor , later receptor-activating effects could also be observed by this substance. This behavior of acting either as an antagonist or as an agonist , depending on the investigation , is also known as functional selectivity . This substance is therefore not an H 3 antihistamine in the strict sense.
chemistry
Stereochemistry
Cipralisant has two stereocenters on the cyclopropane ring. Thus, cipralisant can exist in four different stereoisomeric forms. The (1 S , 2 S ) -form [(1 S , 2 S ) -4- (2- (5,5-dimethylhex-1-ynyl) -cyclopropyl) imidazole] could be identified as the pharmacologically active stereoisomer .
synthesis
The synthesis of Cipralisant takes place in a multistage synthesis starting from trans - urocanic acid by esterification with 2-butanol . After the imidazole ring has been protected by tritylation , the esterification product is reacted with trimethylsulfonium iodide to form the cyclopropane derivative and then saponified. After a racemate resolution , the reaction product is reduced to (1 S , 2 S ) -2- (1-trityl-1 H -imidazol-4-yl) -cyclopropanecarbaldehyde. After conversion to (1 S , 2 S ) -4- [2- (5,5-Dimethylhex-1-ynyl) -cyclopropyl] -1-trityl-1 H -imidazole, the trityl protective group is split off hydrolytically, with the eutomer des Cipralisants is obtained.
Individual evidence
- ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
- ↑ Evaluate group: Gliatech Announces Initiation of Phase II Clinical Trial Perceptin .
- ↑ Tedford CE, Hoffmann M, Seyedi N, et al : High antagonist potency of GT-2227 and GT-2331, new histamine H3 receptor antagonists, in two functional models . In: Eur. J. Pharmacol. . 351, No. 3, June 1998, pp. 307-311. doi : 10.1016 / S0014-2999 (98) 00396-3 . PMID 9721022 .
- ↑ Krueger KM, Witte DG, Ireland-Denny L, et al : G protein-dependent pharmacology of histamine H3 receptor ligands: evidence for heterogeneous active state receptor conformations . In: J. Pharmacol. Exp. Ther. . 314, No. 1, July 2005, pp. 271-281. doi : 10.1124 / jpet.104.078865 . PMID 15821027 .
- ↑ a b Liu H, Kerdesky FA, Black LA, et al : An efficient multigram synthesis of the potent histamine H3 antagonist GT-2331 and the reassessment of the absolute configuration . In: J. Org. Chem. . 69, No. 1, January 2004, pp. 192-194. doi : 10.1021 / jo035264t . PMID 14703397 .