Novel potential nonsedating H1 antagonists related to the gauche rotamer of PROS-NH-histamine

Autor: Rasha Y. Elbayaa, R. M. Shafik, Mona M. El-Semary, Manal N. S. Saudi, Farid S. G. Soliman
Rok vydání: 2008
Předmět:
Zdroj: Medicinal Chemistry Research. 18:187-205
ISSN: 1554-8120
1054-2523
DOI: 10.1007/s00044-008-9119-y
Popis: On the basis of the most stable stereorotameric (R) forms of πNH-histamine (2), the trans (1-TR) and gauche (1-GR) forms have both been reported to be involved in potentiation of H1-receptors. Apart from the known classic models of H1-antagonists that mostly belong to 1-TR, a new topographic receptor map for 1-GR has been postulated. Twenty-seven new compounds pertaining to novel nonclassic molecular models related to 1-GR have been postulated as potential nonsedating, less toxic H1-antagonists. Representative members of the new agents were investigated for H1-blocking activity by using isolated segments from guinea pig ileum. Many of the tested new compounds exhibited activities comparable to that of acrivastine as a reference nonsedating drug. The C log P values of the new agents were lower than that of acrivastine (4.34), which might indicate decreased tendency to cross the blood–brain barrier. The most pronounced activity was displayed by the 5-substituted aminomethylenepyrimidine-2,4,6-triones (21, 23) since they displayed nearly equal 50% inhibition concentrations (IC50) (6.12 × 10−6 M) and lower C log P values.
Databáze: OpenAIRE
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