Cipralisant

(1S, 2S ) -4 - ( 2 - ( 5,5- dimethylhex -1 -ynyl ) -cyclopropyl ) imidazole

Antihistamines

Selective histamine H3 ligand

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Cipralisant (GT- 2331 ) is a standard developed by the company Gliatech drug from the group of H3 antihistamines. This substance was one of the first clinically studied H3 antihistamines and has been tested in phase II trials for the treatment of attention-deficit/hyperactivity disorder in the early 2000s. Another clinical examination and approval for the therapy is not done after the takeover of Gliatech by MSD Sharp & Dohme.

Pharmacology

Although Cipralisant was originally identified as an antagonist at the histamine H3 receptor, and later receptor activating effects could be observed by this substance. This behavior to act, depending on the analysis, either as an antagonist or as an agonist is also referred to as functional selectivity. Thus, this substance no H3 - antihistamine in the actual possible sense,

Chemistry

Stereochemistry

Cipralisant has on the cyclopropane ring two stereocenters. Cipralisant thus may be in the form of four different stereoisomeric forms. [- ( - ( 5,5- dimethylhex -1 -ynyl ) -cyclopropyl 2) imidazole, (1S, 2S )-4 ] can be identified as the pharmacologically active stereoisomer has the (1S, 2S )-form.

Synthesis

The synthesis of Cipralisant is prepared starting from trans -urocanic acid in a multi -step synthesis by esterification with 2 -butanol. After protection of the imidazole ring by tritylation the esterification with trimethylsulphonium is converted to the cyclopropane derivative and subsequently hydrolyzed. After a resolution is the reaction product of (1S, 2S ) -2 - (1- trityl -1H- imidazol-4 -yl) cyclopropanecarbaldehyde reduced. After conversion to (1S, 2S ) -4 - [2 - ( 5,5- dimethylhex -1 -ynyl ) -cyclopropyl ]-1- trityl -1H- imidazole The trityl - protecting group is eliminated by hydrolysis, the eutomer of the receive Cipralisants will.