Sythesis And Studies On Chiral Antagonists Of M Receptors

Chirality is one of the essence attributes of nature. Recently the chiral NCE(new chemical entity) is the new reaserch yield in search of novel drugs. Because many vital diseases such as Parkinsonian syndromes, Alzheimer's disease, chronic obstructive pulmonary disease(COPD) and irritable bowel syndrome are associated with M receptors, more and more attention has been paid to the research on M receptor antagonists. However, the lack of receptor subtype selectivity or organ specificity of M receptor antagonists limited their clinical application. It has been well established that the receptor selectivity and organ specificity not only depends on the chemical properties but also the stereochemical properties. This dissertation focuses on the study of stereochemistry, pharmacology and toxicology of the chiral M receptor antagonists. First, the enationmers of these chiral molecules will be prepared with the application of stereoselective synthesis or chiral separation technology. Then, the differences in M receptor affinity and toxicology between these enationmers will be investigated.