DESIGN AND SYNTHESIS NOVEL COMPOUNDS OF ORTHO-COUMARIC ACID DERIVATES AS ANTI-THROMBOTIC CANDIDATE

It has been reported that aspirin and P2Y inhibitors have emerged as the preferred therapeutic agents for managing vaso-occlusive illness due to their anti-thrombotic properties. However, complaints about the side effects of these drugs are still being reported. Ongoing research is being conducted on the design and development of novel antithrombotic agents to obtain good health and well-being. ortho-Coumaric acid derivates were designed using the ChemDraw program, while a physicochemical prediction study was carried out by the Swiss ADME program, and the MOE platform was operated to predict the activity of the ortho-Coumaric derivates against cyclooxygenase-1. The structural modification of carboxylic acid and phenolic moieties generated ester and thiourea derivatives, thereby increasing the S score of these derivatives, was compared to ortho-coumaric acid. All derivatives have adequate oral absorption (55-85%). Microwave-assisted nucleophilic acyl substitution was operated to produce thiourea derivatives of ortho-coumaric acid using ortho-methoxy cinnamic acid, one of the ortho-coumaric acid derivates, as the starting material for reacting with substituted aniline. This method produced novel compounds in yields of 60-70 percent, depending on the substituent of the aniline compound. The structure of all product reactions was confirmed by UV & IR spectrophotometer,¹ HNMR,¹³ CNMR, and HR-ESI-MS spectrometer. The thiourea moiety of ortho-coumaric derivates interacts similarly with aspirin. The majority of ortho-coumaric derivates have a higher level of interaction with cyclooxygenase-1 compared to ortho-coumaric acid. All of the derivatives exhibited favorable characteristics for oral absorption. Therefore, it may be inferred that these derivatives possess potential as agents with anti-thrombotic properties.