Novelli F, Sparatore F
Istituto di Scienze Farmaceutiche, Università di Genova, Italy.
Farmaco. 1993 Aug;48(8):1021-49.
The (quinolizidin-1 alpha-yl)methanthiol (thiolupinine) was prepared and, utilizing the thiol group reactivity, several S-substituted derivatives were obtained among which was a group of 3-[(lupinylthio)methyl]indoles. Eight of the prepared compounds were subjected to a broad pharmacological screening that evidentiated for many of them good level of the following activities in vivo and in vitro: antiarrhythmic, local anesthetic, negative chronotropic on isolated atria, calcium antagonism on ileum and atria, inhibition of spontaneous contraction of isolated trachea, inhibition of guinea pig ileum contractions induced by angiotensin I and II, bradykinin and cholecystokinin, inhibition of platelet aggregation induced by PAF and ADP. Single compounds were remarkable for additional antagonistic activities: 4 against P1-purine receptor, 8 against substance P, 12 against methacholine and 13 strongly inhibited arachidonate induced platelet aggregation. Very peculiar was the ability of compound 6 to protect mice from PAF induced mortality.
制备了(喹诺里西丁-1α-基)甲硫醇(硫代羽扇豆碱)，并利用硫醇基团的反应活性，得到了几种S-取代衍生物，其中包括一组3-[(羽扇豆硫基)甲基]吲哚。对所制备的8种化合物进行了广泛的药理学筛选，结果表明其中许多化合物在体内和体外均具有以下良好水平的活性：抗心律失常、局部麻醉、对离体心房的负性变时作用、对回肠和心房的钙拮抗作用、抑制离体气管的自发收缩、抑制血管紧张素I和II、缓激肽和胆囊收缩素诱导的豚鼠回肠收缩、抑制PAF和ADP诱导的血小板聚集。单一化合物还具有其他拮抗活性：化合物4对P1-嘌呤受体有拮抗作用，化合物8对P物质有拮抗作用，化合物12对乙酰甲胆碱有拮抗作用，化合物13强烈抑制花生四烯酸诱导的血小板聚集。化合物6保护小鼠免受PAF诱导死亡的能力非常独特。
