Study On The Synthesis And In Vitro Pharmacological Activities & Cytotoxicity Of 4-methoxy Phthalamides(Sulfonamides)

Thromboembolism is the disease that has threaten people’s health since the 21st century and has become the leading cause of death in the world’s population.Antiplatelet aggregation drugs can suppress the formation of blood clots.At present,TXA₂ inhibitors and factor Xa inhibitors have been the research hotspots of antiplatelet drugs.Picotamide is an antiplatelet drug with TXA₂ synthetase inhibitory effect.In this paper,picotamide is used as a lead compound.Ten kinds of 4-methoxy-1,3-phthalamide type target compounds（PN775-PN784）were synthesized.By using the bioisosteric principle,the amide structure was replaced by a sulfonamide structure,and ten kinds of 4-methoxy-1,3-benzenedisulfonamide target compounds（PN785-PN794）were synthesized.Betraxaban is a factor Xa inhibitor that inhibits thromboxane A₂ synthase.Eight kinds of 3-amino-4-methoxybenzamides were synthesized with reference to the asymmetric acyl structure of betrixaban.The target compounds of the amide series（PN795-PN802）.None of the 28 target compounds were reported in the literatur.The inhibitory activities of the eight compounds were superior to the positive control drugs picotamide and aspirin.Compound PN779 had the highest inhibition rate when using AA and collagen as inducers,and was superior to the two positive control drugs picotamide and aspirin.In the methoxysulfonamide series,In the methoxyamide series,target compound PN781 has cell viability at 10μmol/L and 100μmol/L higher than picotamide.Both series of compounds have further research value.