Study On The Design, Synthesis And Activity Of Novel β - Adenosine - Adrenergic Receptor Agonists

β₂-adrenoceptor agonists are one of the first-considered drugs in the condition of acute asthma.They can relieve the tension of the smooth muscles quickly of bronchus and the symptom of asthma.In this thesis,the pathogenesis of the asthma was described concisely;the structure ofβ₂-adrenoceptor and the action mechanism ofβ₂-adrenoceptor agonists were introduced systematically at the molecular level.At the same time,the development and structure-activity relationship ofβ₂-adrenoceptor agonists were reviewed.Homology modeling was taken in the process of structure construction and the results were evaluated by PROCHECK and the model was better than the template.On the other hand,nearly 100 2-phenyl-2-amino ethanol derivatives which were synthesized by our lab and their pharmacological values were used in the CoMFA study.The QSAR model was summarized from this study and used in the further ligand-based drug design.Based the CoMFA studies,27 derivatives of phenylethanolamines,including 1 derivatives （C27）as 1-phenyl-2-amino-ethanols and 26 derivatives（C01～C26）as 2-phenyl-2-amino-ethanols, were designed and synthesized on the principle of isosterism with tranditerol,which is a high efficiency,high selectivity and specialty of leading compound.All compounds were characterized by ¹H-NMR and MS,in which C08 is the isomeric compounds of C27.The two structures were compared from the differences of their spectra by the two compounds of C08 and C27.Furthermore,the mechanism of the reactions forming the two types of compounds was discussed either.Preliminary pharmacological tests showed that these compounds had agonistic activity on theβ₂-adrenoceptor and futher study is undertaken.