الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Among the most conspicuous ion channels are L-type Ca+2 channels (LCC). These are membrane heteromultimeric proteins that allow selective entrance of Ca+2 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: 1,4dihydropyridines (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 the synthesis of fully 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 parts of the present thesis. They are arranged in accordance with their appearance in the thesis as follows:
Chapter 1: Introduction
It represents a brief literature survey on the most biologically active substituted pyrimidine derivatives that include anticancer, antiviral, antimicrobial, anti-inflammatory and cardiovascular drugs.
Chapter 2: Aim of the work
It deals with the rationale upon which the newly suggested compounds were designed. Synthetic routes for preparation of target compounds are depicted in Schemes 1-5
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 by elemental analyses and various spectroscopic techniques (IR, 1H-NMR, 13C-NMR, and Mass spectra).
It is subdivided into five parts as follows:
Part I (Scheme 1): It discusses the preparation of the key intermediates: Ethyl 2-cyano-3-arylacrylates (1,2), from the reaction of substituted benzaldehyde with ethyl cyanoacetate and 2-(ethoxyalkylidene)malononitriles (3a,b) and Ethyl 2-cyano-3-ethoxybut-2-enoate (3c), from the reaction of triethyl orthoacetate or orthoformate with ethyl cyanoacetate or malonitrile.