A NEW SCAFFOLD FOR D3 DOPAMINERGIC AFFINITY CONTAINING ARYLPIPERAZINE FRAGMENT: MOLECULAR MODELING, SYNTHESIS, IN VITRO AND IN VIVO PHARMACOLOGICAL EVALUATION | ||||
Bulletin of Pharmaceutical Sciences Assiut University | ||||
Article 13, Volume 30, Issue 2, December 2007, Page 259-273 PDF (378.02 K) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/bfsa.2007.64208 | ||||
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Authors | ||||
Dalal A. Abou El Ella* 1; Franziska K. U. Müller2 | ||||
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, El-Khalifa El-Maamoon St., 11566, Abbassia, Cairo, Egypt | ||||
2Biological Screening Units, Institute of Pharmacy, Philosophenweg 14, D-07743 Jena, Germany | ||||
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. | ||||
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