الفهرس 
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Abstract
A novel series of α1-adrenoreceptor antagonists with6-methyl-4,5,6,7-
tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid amide and 5,6,7,8-
tetrahydropyrido[4’,3’:4,5]-thieno[2,3-d]-pyrimidin-4(3H)-one rings attached to
different 2 or 3-substituted phenylpiperazines were designed and their molecular
modeling simulation studies were done using Discovery Studio 2.5(Accelerys,
San Diego, CA).
Significant number of compounds showed high fitting scores. The designed
compounds were synthesized and their α1-adrenoreceptor blocking activity was
evaluated through functional bioassay against prazosin (35), where they showed
significant antagonistic activity ranging from 46.37% blockade up to 94.74 %.
Structure activity relationship of the investigated compounds:
1- The substitution on the phenyl ring of the arylpiperazine is crucial
element for the α1-ARs blocking activity. As in the Xa-d series, there was
a decrease in the activity by changing the substitution on the phenyl ring in the following order o-methoxy (94.74 % ) ˃ m-chloro (86.46%) ˃ unsubstituted (77.93%) ˃ o-flouro (65.68%). The same was observed in
the IXa-c series; where compound IXb showed the highest activity among this series (78.27%) compared to 46.37% for the
unsubstitutedIXa. Also, in VIIa-dseries, o-methoxy has great effect on the activity where compound VIIbshowed 76.76% blocking activity
compared to 69.93% for the m-chloro substituted VIId. Unexpectedly in VIa-c series,VIcwitho-flouro substitution showed 88.88% blocking activity compared to o-methoxy VIb (81.15%).Thus the presence of a methoxy group at the ortho position seems optimum for the activity.