硫双肼类型化合物抑制单胺氧化酶的化学结构与作用关系的研究

STUDIES ON STRUCTURE-ACTIVITY RELATIONSHIP OF ANALOGS OF TAPHA—A MAOI

摘要: 本文应用体外抑制脑和肝内MAO活力的试验,比较了51种硫双肼类似物,从中选出抑制作用较强者,进行体内抑制MAO活力试验,和急性毒性比较。试验证明,硫酰肼类型化合物的体内抑制作用比等电原子—氮酰肼类型,或氧酰肼类型要强大(硫酰肼类最强,氮酰肼类其次,氧酰肼类最弱)。后两类型化合物可能不易透过血脑屏障。硫酰肼的烷基化的有效基团(R)为异丙基、丁基、苄基、苯乙基,毒性以异丙基最小。硫酰肼中丙酰基或乙酰基的作用差异不显著。硫双肼的作用集中了上述三个组分的优点,故它的毒性甚低(LD₅₀5170mg/kg)。Y:—S—,—O—,—O—CH₂—CH₂—O—,R—N<.n:1.2. 硫双肼Y:—S—,R:—CH(CH₃)₂,n:2

Abstract: 4-Thioheptane-1,7-di-oyl-bis-isopropyl-hydrazide (Tapha, or CH-6) is a new monoamine oxidase inhibitor (MAOI) with low toxicity. With regard to inhibiting potency on MAO, there are a number of structural requirements which appear well defined (Ⅰ), such as thio-ether linkage, isopropyl group and propionyl (or acetyl) radical, beside the hydrazine moiety. Taphan acquires all these requirements (isopropyl, -S-, n=2), and its favourable pharmacological actions are understandable.