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Conformation and Bioactivity. Design and Discovery of Novel Antihypertensive Drugs

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Peptidomimitism is applied to the medicinal chemistry in order to synthesize drugs that devoid of the disadvantages of peptides. AT1 antagonists constitute a new generation of drugs for the treatment of hypertension designed and synthesized to mimic the C-terminal segment of Angiotensin II and to block its binding action on AT1 receptor. An effort was made to understand the molecular basis of hypertension by studying the conformational analysis of Ang II and its derivatives as well as the AT1 antagonists belonging to SARTANs class of molecules. Such studies offer the possibility to reveal the stereoelectronic factors responsible for bioactivity of AT1 antagonists and to design and synthesize new analogs. An example will be given which proves that drugs with better pharmacological and financial profiles may arise based on this rational design.
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Keywords: AT1 antagonists; Antihypertensive Drugs; C-terminal segment

Document Type: Review Article

Affiliations: Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, Vas. Constantinou 48, Athens 11635.

Publication date: February 1, 2004

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