Clemizole
Chemical compound
From Wikipedia, the free encyclopedia
Clemizole, sold under the brand names Allercur and Histacur, is a histamine H1 receptor antagonist of the benzimidazole group described as an antihistamine, antipruritic, and sedative which is no longer marketed.[1][2][3][4] It is a first-generation antihistamine.[5]
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| Trade names | Allercur, Histacur |
| Other names | EPX-100 |
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| ECHA InfoCard | 100.006.486 |
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| Formula | C19H20ClN3 |
| Molar mass | 325.84 g·mol−1 |
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It is also a serotonin receptor agonist and is being studied for the potential treatment of Dravet syndrome, Lennox–Gastaut syndrome, and epilepsy under the development code name EPX-100.[6][4][7] The drug is said to act specifically as a serotonin 5-HT2 receptor agonist,[8][9] with prominent affinity for the serotonin 5-HT2A and 5-HT2B receptors having been reported.[5][4] On the other hand, it showed markedly lower affinity for the serotonin 5-HT2C receptor.[4] Clemizole also showed affinity for several other receptors.[4]
The drug was first described in the scientific literature by 1952.[1] Its serotonin receptor agonist and anticonvulsant properties were discovered in 2017.[6][4]
Chemistry
Synthesis
Benzimidazoles substituted with an alkylamine at position 2 have a venerable history as H1 antihistaminic agents. The standard starting material for many benzimidazoles consists of phenylenediamine, or its derivatives.
Reaction of that compound with chloroacetic acid can be rationalized by invoking initial formation of the chloromethyl amide. Imide formation with the remaining free amino group closes the ring to afford 2-chloromethyl benzimidazole (3). Displacement of halogen with pyrrolidine affords the alkylation product. The proton on the fused imidazole nitrogen is then removed by reaction with sodium hydride. Treatment of the resulting anion with α,4-dichlorotoluene gives the H1 antihistaminic agent clemizole (5).