276687-52-6Relevant articles and documents
Design, synthesis and antihistaminic (H1) activity of some condensed 3- aminopyrimidin-4(3H)-ones
Shishoo, Chamanlal J.,Shirsath, Vikas S.,Rathod, Ishwarsinh S.,Yande, Vikas D.
, p. 351 - 358 (2007/10/03)
A novel series of condensed 3-amino-2-(substituted)methylpyrimidin- 4(3H)-ones is reported with potential H1 receptor antagonistic activity. The IC50 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 pA2 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 -NHSO2- 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 -NHSO2- in the side chain exhibit a closer fit with temelastine than their -O- isosteres. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
