Synthesis and biological evaluation of n-butylphthalide derivatives as anti-platelet aggregation agents

Abstract

New analogues of n-butylphthalide (NBP) bearing various lengths of alkyl and different substitution at the two-position of phthalide were designed and synthesised. Preliminary evaluation and prediction of ACD LogP software indicate that the derivatives display significant improvement in water solubility than NBP does. Further biological analysis showed that NBP analogues specifically inhibit platelet aggregation induced by arachidonic acid but have no effect on that induced by adenosine 5-diphosphate. Especially compounds 1 and 3 were stronger than classical anti-platelet drug, aspirin, and equal potent with NBP, respectively. These findings provide an alternative approach to the development of NBP analogues with anti-platelet aggregation activity with good water solubility for the intervention of ischemic stroke.

Keywords:

• n-Butylphthalide analogues
• water solubility
• anti-platelet aggregation

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This study was supported by and in part by National Natural Science Foundation of China [grant number 81273782] to D Lin.