Based On "a Combination Of Traditional Chinese Medicine Molecular Chemistry" Design, Synthesis Of Small Molecules And Their Inhibitory Activity Of Angiotensin Converting Enzyme

Theoretical treasure trove of Chinese medicine for thousands of years of wisdom condensed in guiding new drug research and development play endless advantages. On the basis of "Jun shi drugs", "Jun shi compounds", "Jun chen zuo shi compounds ", we deeply study the structure of the medicine angiotensin-converting enzyme inhibitors and drug molecules with antihypertensive activity in traditional Chinese medicine group. With the design concept of traditional Chinese medicine "fang zheng zu fang" as the guiding ideology, using the design method of "combination of traditional Chinese medicine molecular chemistry", we designed and synthesized eight new analogues of angiotensin converting enzyme inhibitors. After the activity test in vivo and vitro, we preliminarily get 2 compounds which in the inhibition of angiotensin converting enzyme and the antihypertensive effect are good. The full text is divided into the following three parts to study:(1) Using the drug design method of "combination of traditional Chinese medicine molecular chemistry", we established different functions of the compound library and a connection between each compound libraries molecules, designed and identified the general structural formula of angiotensin converting enzyme inhibitor analogs, which enriched our group designed 221S series compound libraries before.(2) We determined the synthetic route, synthesized eight new analogs of angiotensin-converting enzyme inhibitors. By MS, NMR structural identification, each molecular structure is correct.(3) We preliminarily study the above eight new compounds on the activity of angiotensin-converting enzyme inhibition and spontaneously hypertensive (SHR) rats antihypertensive activity in vivo and vitro. The results show that:1. Eight compounds have the effect in inhibiting ACE in vitro activity test experiments, but the IC50 were higher than positive drug captopril.2. ACE ELISA test in mice and Antihypertensive activity tests in SHR rats showed that 134,149 compounds can inhibit the angiotensin-converting enzyme slightly better positive drug captopril. 属性不符...