A NEW SCAFFOLD FOR D3 DOPAMINERGIC AFFINITY CONTAINING ARYLPIPERAZINE FRAGMENT: MOLECULAR MODELING, SYNTHESIS, IN VITRO AND IN VIVO PHARMACOLOGICAL EVALUATION

Abou El Ella, Dalal A.; U. Müller, Franziska K.

doi:10.21608/bfsa.2007.64208

A NEW SCAFFOLD FOR D3 DOPAMINERGIC AFFINITY CONTAINING ARYLPIPERAZINE FRAGMENT: MOLECULAR MODELING, SYNTHESIS, IN VITRO AND IN VIVO PHARMACOLOGICAL EVALUATION

Document Type : Original Article

Authors

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, El-Khalifa El-Maamoon St., 11566, Abbassia, Cairo, Egypt

² Biological Screening Units, Institute of Pharmacy, Philosophenweg 14, D-07743 Jena, Germany

10.21608/bfsa.2007.64208

Abstract

A new series of N-(6-substitutedbenzo[d]thiazol-2-yl)-2-(4-
arylpiperazin-1-yl) acetamides (3a-f) and 2-(3-(4-arylpiprazin-1-
yl)propylthio)benzo[d]thiazoles/-oxazoles/-imidazole (6a-f) was
synthesized by connecting arylpiperazine through a semi-rigid or
flexible spacer to a heterocyclic moiety, respectively. The
radioligand binding experiments for the D1, D2, D3 and D5 subtypes
expressed in CHO cells were examined for the target compounds
3a-f, 6a, 6b, 6d and 6f. Compound 6a showed the best binding
affinity for dopamine D3 receptor and is considered as a new
scaffold for D3 dopaminergic affinity. Furthermore, molecular
modeling of the best-fitted conformer of target compounds 3a, 6b,
6c, 6d and 6f to 
1-adrenoceptor ( 
1-AR) antagonist hypothesis
was performed using CATALYST software, HipHop modules. Based
on the results of simulation studies, these target compounds were
evaluated for their in vivo hypotensive activity on blood pressure of
normotensive cats.