Synthesis Of Novel Bradykinin B2Receptor Antagonists

As a series of drugs that are able to effectively work on human Bradykinin B2Receptor, Bradykinin B2Receptor Antagonists have definite effect on some clinical diseases such as asthma, pancreatitis, Alzheimer’s Disease, traumatic brain injury, allergic rhinitis, angioedema, osteoarthritis, etc. Much more attentions have been paid to this kind of drugs since it was discovered. In recent years, some groups have designed and synthesized lots of Bradykinin B2Receptor Antagonists containing good biological activity through doing further research on the specific structure and activity relationship (SAR). Some novel antagonists have been used for clinical test and proved to be potential drugs. So it does make great sense for human health to do more study on the Bradykinin B2Receptor Antagonists.Based on the SAR of these kinds of drugs and great works that have been done by Fujisawa Pharmaceutical Co. Ltd., two kinds of non-peptide Bradykinin B2Receptor Antagonists were synthesized, and the synthetic route was explored and optimized. Specifically as follows: Beginning with2,6-dichlorotoluene, a series of B2Receptor Antagonists were synthesized through multi-step reactions, such as Fridel-Crafts acylation, esterification, bromination, substitution, hydrolysis and etc. Preliminary exploration for synthesis of another designed kind of Antagonists was already done.