申请人:Teijin Limited
公开号:US04466980A1
公开(公告)日:1984-08-21
A novel compound selected from the group consisting of 7-(or 6- or 4-)thiaprostaglandin E.sub.1 derivatives of the formula (I). ##STR1## wherein A represents --CH.sub.2 -- or ##STR2## in which n is 0, 1 or 2, provided that only one A cut of three is ##STR3## R.sup.1 -R.sup.7 and G are as defined in the specification, the 15-epimers of said thiaprostaglandin E.sub.1 derivatives, the enatiomers of said thiaprostaglandin E.sub.1 derivatives or their 15-epimers, and mixtures of these compounds. A 7-thiaprostaglandin E.sub.1 derivative and/or its optical isomer may be prepared by reacting a 2-organo-2-cyclopentenone (II) with an organic copper-lithium compound (III) to effect conjugation reaction. A 6-thiaprostaglandin E.sub.1 derivative and/or its optical isomer may be prepared by subjecting an .alpha.,.beta.-unsaturated ketone (IV) and a thiol (V) to the Michael addition reaction. And, 4-thiaprostaglandin derivative and/or its optical isomer may also be prepared by the Michael addition reaction from a 2-allyl substituted cyclopentanone (VI) and a thiol (VIII). Some compounds ((I)-1) amongst the compounds of the formula (I) and/or their optical isomer are useful for controlling vascular actions such as angina pectoris, vasodilation etc.
从以下化合物组中选择一种新的化合物,该组化合物包括公式(I)的7-(或6-或4-)硫代前列腺素E.sub.1衍生物。其中,A表示--CH.sub.2--或##STR2##其中n为0、1或2,前提是只有一个A切口为三个##STR3##R.sup.1-R.sup.7和G如规范中所定义,所述硫代前列腺素E.sub.1衍生物的15-表异构体,所述硫代前列腺素E.sub.1衍生物的对映异构体或其15-表异构体,以及这些化合物的混合物。可以通过将2-有机-2-环戊酮(II)与有机铜锂化合物(III)反应以进行共轭反应来制备7-硫代前列腺素E.sub.1衍生物和/或其光学异构体。可以通过将α,β-不饱和酮(IV)和硫醇(V)进行Michael加成反应来制备6-硫代前列腺素E.sub.1衍生物和/或其光学异构体。此外,也可以通过从2-烯丙基取代的环戊酮(VI)和硫醇(VIII)进行Michael加成反应来制备4-硫代前列腺素衍生物和/或其光学异构体。公式(I)的化合物((I)-1)中的某些化合物和/或其光学异构体对于控制血管作用,如心绞痛、血管扩张等非常有用。