"Design, synthesis and pharmacological evaluation of some substituted d" by Mohamed Teleb, Ola H. Rizk et al.

Faculty Publications

Title

Design, synthesis and pharmacological evaluation of some substituted dihydropyrimidines with L-/T-type calcium channel blocking activities

Authors

Mohamed Teleb, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
Ola H. Rizk, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria 21311, Egypt.
Fang-Xiong Zhang, Department of Physiology & Pharmacology, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary T2N 4N1, Canada.
Frank R. Fronczek, Department of Chemistry, College of Science, Louisiana State University, Baton Rouge, LA 70803, USA.
Gerald W. Zamponi, Department of Physiology & Pharmacology, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary T2N 4N1, Canada.
Hesham Fahmy, Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA. Electronic address: Hesham.Fahmy@sdstate.edu.

Document Type

Article

Publication Date

3-1-2019

Abstract

New dihydropyrimidines bearing various lipophilic pharmacophores and functionalities at position 3 were designed and synthesized. The basic framework of the new compounds was designed to maintain the main structural requirements for calcium channel blocking activity of the known dihydropyridines and dihydropyrimidines calcium channel blockers. The newly synthesized compounds were evaluated as antagonists for Ca1.2 and Ca3.2 using the whole-cell patch clamp technique. Seven compounds (4b, 4c, 6c, 9, 13c, 13e and 17b) showed promising dual calcium channel blocking activity and three compounds (13b, 14b and 17a) were selective against Cav3.2. Their drug-likeness has been assessed using Molinspiration and Molsoft softwares. Their physicochemical properties and pharmacokinetic profiles recommend that they can be considered as drug-like candidates.

Publication Source (Journal or Book title)

Bioorganic chemistry

First Page

354

Last Page

366

Recommended Citation

Teleb, M., Rizk, O. H., Zhang, F., Fronczek, F. R., Zamponi, G. W., & Fahmy, H. (2019). Design, synthesis and pharmacological evaluation of some substituted dihydropyrimidines with L-/T-type calcium channel blocking activities. Bioorganic chemistry, 83, 354-366. https://doi.org/10.1016/j.bioorg.2018.10.054

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