In GPIIb/IIIa mediated arterial thrombosis platelet activation plays a central role. To discover platelet activation inhibitor the pharmacophores of GPIIb/IIIa receptor inhibitors and anti-thrombotic agents were analyzed. This led to the design of (1R,3S)- and (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acids as GPIIb/IIIa inhibitors. Comparing to (1S,3S)-isomer (1R,3S)-isomer had lower cdocker interaction energy. AFM image showed that the minimal effective concentration of (1S,3S)-isomer and (1R,3S)-isomer inhibiting platelet activation were 10⁻⁵ M and 10⁻⁶ M, respectively. In vivo 1 μmol/kg of oral (1S,3S)-isomer effectively inhibited the rats to form arterial thrombus and down regulated GPIIb/IIIa expression, but the activities were significantly lower than those of 1 μmol/kg of oral (1R,3S)-isomer. Both (1S,3S)-isomer and (1R,3S)-isomer can be safely used for structural modifications, but (1R,3S)-isomer should be superior to (1S,3S)-isomer.

在GPIIb / IIIa介导的动脉血栓形成中，血小板活化起着核心作用。为了发现血小板活化抑制剂，分析了GPIIb / IIIa受体抑制剂和抗血栓形成剂的药效团。这导致设计了（1 R，3 S）-和（1 S，3 S）-1-甲基-1,2,3,4-四氢-β-咔啉-3-羧酸作为GPIIb / IIIa抑制剂。与（1 S，3 S）-异构体相比（1 R，3 S）-异构体具有较低的cdocker相互作用能。AFM图像显示（1 S，3 S）-异构体和（1 R，3 S）-异构体抑制血小板活化分别为10 ^-5  M和10 ^-6M  。体内1μmol/ kg口服（1 S，3 S）异构体可有效抑制大鼠形成动脉血栓并下调GPIIb / IIIa表达，但活性明显低于1μmol/ kg口服（1 S，3 S）异构体（1 R，3S）-异构体。（1 S，3 S）-异构体和（1 R，3 S）-异构体均可安全用于结构修饰，但（1 R，3 S）-异构体应优于（1 S，3 S）-异构体。