Synthesis Of A Novel Class Of Bradykinin B₂ Receptor Antagonists

Considering the global status of drugs to treat diseases, the urgency of new drug research and develop has become a consensus. The development of Bradykinin B2 Receptor Agonists has become a hot spot. As a subtype of the endogenous peptide in the human body, B2 receptors are expressed constitutively in most cell and tissue types and mediate most of the known effects of BK (Bradykinin) and KD (Kallidin) when these are produced in plasma or tissues. Recent years, a large number of in vivo studies had shown that the blockade of the B2 receptor may provide therapeutic benefit in pathological conditions such as asthma, allergic rhinitis, pancreatitis, osteoarthritis, traumatic brain injury. So, the development of these drugs is of great importance. From peptide to non-peptide, a diversity of these compounds have been devised and synthesized, and some of them have been proved to be potent in clinical studies. Among them, Fujisawa Pharmaceutical Co. Ltd. in Japan had made outstanding contributions to the area of the non-peptide antagonist drug design and development.According to the Structure-Activity Relationship (SAR) reported in the literature, in this thesis, we designed a novel class of bradykinin B2 receptor antagonists and the proposed route of synthesis. The target compound was a combination of non-peptide based on biologically active 2,6-dichlorotoluene and quinoline substructure and dipeptids molecular in order to make it has their both advantages, not only with a better biological activity, but also with a better water solubility. We preliminary explored the synthesis of the target compounds together with the reactions optimization, and finally we got a more reasonable synthesis route. At the same time, we synthesized many new compounds and made their structures characterized and identificated.