Design And Synthesis Of A New Series Of The Angiotensin Ⅱ Receptor Antagonists

Angiotensin â…¡ receptor antagonists are antihypertension drugs with characterisits of high potension, high safety and were used in clinic widely. They can interdict the AT1 receptor alternatively, thus reduce the blood pressure with low side-effects. In this thesis, the following works have been carried out.1. Based on the stereo-structures of angiotensin II, angiotensin II receptor and the successful development of sartans, we studied the structure-activity relationships(SAR) of angiotensin II receptor antagonists. A series of new AT1 receptor antagonists were designed. 8 new target compounds were synthesized.2. The synthesis methods of Valsartan were taken into account, a synthesis route of target compounds were established. As the primary material, 2-methoxybenzoic acid was transferred into 2-cyano-4'-methybiphenyl then reacted with amino acid ester. After 4 steps the target compounds were obtained3. We choose butyl chloroformate to obtain the stable intermediates instead of ethyl chloroformate and 2-ethyl hexyl chloroformate.4. We studied the alternative and cleavage of the protective groups of amino acids. The method of ester exchange has been used and it can avoid some side reactions.5. QSAR parameter method in Spartan Programe was used to analysize the possible activities of the designed AT1 receptor antagonists.