Patent Evaluation: Novel Imidazole Antihistamines

Summary

Novelty: Novel imidazole derivatives are disclosed which have agonistic and antagonistic activity at the histamine (H₃) receptor. The compounds are potentially useful as antihistamines and a process for their synthesis is claimed.

Biology: The agonistic and antagonistic activities were measured using the method described by Van der Werf et al. (Agents and Actions (1987) 20:34) and Menkveld et al. (Eur. J. Pharm. (1990) 86:343-347). The pA₂ values of the antagonists range from 5.8 to 9.9; pA₂ values of the agonists were in the range 7.3 to 9.3.

Chemistry: Syntheses are described in twenty-one examples. S-[Z-(imidazoyl-4-yl)ethyl]-N-(2-phenylethyl)-isothiourea is one of nine preferred compounds showing antagonistic activity. One agonist is preferred.

Structure: