ChemInform Abstract: Design, Synthesis and Antihistaminic (H1) Activity of Some Condensed 3-Aminopyrimidin-4(3H)-ones

Autor: Vikas S. Shirsath, Vikas D. Yande, I. S Rathod, Chamanlal J. Shishoo
Rok vydání: 2010
Předmět:
Zdroj: ChemInform. 31
ISSN: 1522-2667
0931-7597
DOI: 10.1002/chin.200031167
Popis: Anovel series of condensed 3-amino-2-(substituted)methylpyrimidin-4(3H)-ones is reported with potential H(1) receptor antagonistic activity. The IC(50) values for 23 compounds were found to be in the micromolar range. Five lead compounds (10c, e, g, r and t), when evaluated by the in vivo method were found to protect guinea-pigs from the histamine induced asphyxia and antagonized histamine in a competitive and reversible manner. With a pA(2) value of 8.7 and protection time of 9.5 min (in vivo test), compound 10g was the most active amongst these five compounds. The isosteric replacement of the side chain -NH- in series 1, by oxygen and -NHSO(2)- functions, was undertaken to investigate the role of two amino functions in the receptor binding. This isosteric replacement with -O- does not affect the antihistaminic activity and the sedative potential of the series. Preliminary molecular modelling studies indicate that the compounds with -NHSO(2)- in the side chain exhibit a closer fit with temelastine than their -O- isosteres.
Databáze: OpenAIRE
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