الفهرس 
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Abstract
Among the most conspicuous ion channels are L-type Ca2+ channels (LCC). These are membrane heteromultimeric proteins that allow selective entrance of Ca2+ ions into excitable cells upon membrane depolarization. LCC modulation has found prominent clinical application for treating many vascular disorders especially cardiovascular ones.
To date, just three different chemical categories of LCC targeting drugs exist: 1,4-dihyDROPyridines (DHPs such as nifedipine), phenylalkylamines (PAAs such as verapamil), and benzothiazepines (BTZs such as diltiazem). All of them are extensively used in the treatment of cardiovascular disorders, including hypertension, arrhythmias and angina.
Structure activity relationship study of DHPs; the most widely spread series of CCBs, has lead to the design of their aza analogs. Among these, some Biginelli DHPMs showed outstanding calcium channel blocking activity. In the present work, considerable interest was directed to aromatized DHPMs in view of the fact that DHPMs possess calcium channel blocking activity as DHPs.
Design, synthesis, computational studies as well as pharmacological assessment of target compounds, are presented as the main part of the present thesis. They are arranged in accordance with their appearance in the thesis as follows:
Chapter 1: Introduction
It represents a comprehensive overview on many intriguing aspects of various ion channels encompassing their widespread existence, structures, mode of action and clinical importance. Concerning the very important calcium channels as potential drug targets, a literature survey of their molecular pharmacology as well as chemical modulators especially DHPs and their aza analogs is well documented. In addition, the introductory part reviews the functionalization of the CCB prototype, “Nifedipine”, at various positions of the molecule which has been a target for its modification towards obtaining derivatives that may possess better blockade activities.
Chapter 2: Aim of the work
It deals with the rationale upon which novel pyrimidine derivatives have been designed, synthesized and pharmacologically evaluated for their calcium channel blocking activity. Synthetic routes for preparation of target compounds are depicted in Schemes 1-4.
Chapter 3: Results and Discussion
It discusses the basic concepts of the experimental methods adopted for the synthesis of the designed compounds referring to available literature. It also investigates the structural elucidation of the synthesized compounds via elemental analyses, various spectroscopic
techniques (IR, 1H-NMR, 13C-NMR, DEPT, HMBC and Mass spectra) as well as X-ray crystallographic analyses.