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    • 3. 发明授权
    • 6-substituted prostaglandins E.sub.1 and process for producing same
    • 6-取代的前列腺素E1及其制备方法
    • US4797506A
    • 1989-01-10
    • US794857
    • 1985-10-18
    • Toshio TanakaAtsuo HazatoSeizi Kurozumi
    • Toshio TanakaAtsuo HazatoSeizi Kurozumi
    • C07F7/18A61K31/557A61K31/5575A61P43/00C07C67/00C07C401/00C07C405/00C07F1/02C07F1/08
    • C07C405/0041C07C405/00C07F1/02C07F1/08
    • 6-substituted prostaglandins E.sub.1 which are compounds represented by the following formula [I] or their enantiomers or mixtures whereof in any ratio: ##STR1## wherein R.sup.1 represents a hydrogen atom, a C.sub.1 -C.sub.16 alkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted phenyl C.sub.3 -C.sub.10 cycloalkyl group, a substituted or unsubstituted phenyl (C.sub.1 -C.sub.2) alkyl group, or one equivalent cation; R.sup.2 and R.sup.3, which may be the same or different, represent a hydrogen atom, a tri (C.sub.1 -C.sub.7) hydrocarbon silyl group, or a group forming an acetal linkage together with an oxygen atom of a hydroxyl group; R.sup.4 represents a hydrogen atom, a methyl group or a vinyl group; R.sup.5 represents a linear or branched C.sub.3 -C.sub.8 alkyl group, a linear or branched C.sub.3 -C.sub.8 alkenyl group, a linear or branched C.sub.3 -C.sub.8 alkynyl group, a phenyl group which may be substituted, a phenoxy group which may be substituted, a C.sub.3 -C.sub.10 cycloalkyl group which may be substituted, or a linear or branched C.sub.1 -C.sub.5 alkyl group which may be substituted with a C.sub.1 -C.sub.6 alkoxy group, a phenyl group which may be substituted, a phenoxy group which may be substituted, or a C.sub.3 -C.sub.10 cycloalkyl group which may be substituted; and X represents an ##STR2## group or an oxygen atom. Such 6-substituted prostaglandins E.sub.1 are useful for the treatment and/or prevention of digestive organ diseases such as duodenal ulcers or gastric ulcers.
    • PCT No.PCT / JP85 / 00096 Sec。 371日期:1985年10月18日 102(e)1985年10月18日日期PCT提交1985年2月28日PCT公布。 第WO85 / 03935号公报 日期:1985年9月12日.6-取代的前列腺素E1,其为下式[I]表示的化合物或其对映异构体或其任何比例的混合物:其中R1表示氢原子,C1-C16烷基 取代或未取代的苯基,取代或未取代的苯基C3-C10环烷基,取代或未取代的苯基(C1-C2)烷基或一个当量的阳离子; R2和R3可以相同或不同,表示氢原子,三(C1-C7)烃甲硅烷基或与羟基的氧原子一起形成缩醛键的基团; R4表示氢原子,甲基或乙烯基; R 5表示直链或支链C 3 -C 8烷基,直链或支链C 3 -C 8烯基,直链或支链C 3 -C 8炔基,可被取代的苯基,可被取代的苯氧基,C3 可被取代的C 10环烷基,或可以被C 1 -C 6烷氧基取代的直链或支链C 1 -C 5烷基,可被取代的苯基,可被取代的苯氧基或C3 可被取代的-C 10环烷基; X表示基团或氧原子。 这种6-取代的前列腺素E1可用于治疗和/或预防消化器官疾病如十二指肠溃疡或胃溃疡。
    • 4. 发明授权
    • 7-thiaprostaglandins E, and process for producing same
    • 7-硫代前列腺素E及其制备方法
    • US5159102A
    • 1992-10-27
    • US526682
    • 1990-05-22
    • Toshio TanakaKiyoshi BannaiAtsuo HazatoSeizi Kurozumi
    • Toshio TanakaKiyoshi BannaiAtsuo HazatoSeizi Kurozumi
    • C07C405/00
    • C07C405/0033
    • 7-thiaprostaglandins E.sub.1 which are compounds represented by the following formula [I] or their enantiomers or mixtures thereof in any ratio: ##STR1## where R.sup.1 represents a hydrogen atom, a C.sub.1 -C.sub.10 alkyl group, a C.sub.2 -C.sub.20 alkenyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted C.sub.3 -C.sub.10 cycloalkyl group, a substituted or unsubstituted phenyl (C.sub.1 -C.sub.2) alkyl group, or one equivalent cation; R.sup.2 and R.sup.3, which may be the same or different, represent a hydrogen atom, a tri (C.sub.1 -C.sub.7) hydrocarbon silyl group, or a group forming an acetal linkage together with an oxygen atom of a hydroxyl group; R.sup.4 represents a hydrogen atom, a methyl group or a vinyl group; R.sup.5 represents a linear or branched C.sub.3 -C.sub.8 alkyl group, a linear or branched C.sub.3 -C.sub.8 alkenyl group, a linear or branched C.sub.2 -C.sub.8 alkynyl group, a phenyl group which may be substituted, a phenoxy group which may be substituted, a C.sub.3 -C.sub.10 cycloalkyl group which may be substituted, or a linear or branched C.sub.1 -C.sub.5 alkyl group which may be substituted with a C.sub.1 -C.sub.6 alkoxy group, a phenyl group which may be substituted, a phenoxy group which may be substituted or a C.sub.3 -C.sub.10 cycloalkyl group which may be substituted; X represents an ethylene group, a vinylene group or an ethylene group; n represents 0 or 1; the expression represents an ethylene group or a vinylene group, provided that when n is o and x is an ethylene group, R.sup.5 is not a linear or branched C.sub.3 -C.sub.8 alkyl group or a C.sub.3 -C.sub.10 cycloalkyl group which may be substituted.Such compounds are especially useful for the treatment and prevention of digestive organ diseases such as a duodenal ulcer or a gastric ulcer.
    • 作为由下式[I]表示的化合物或其对映异构体或其混合物的7-硫代前列腺素E1为任意比例:其中R 1表示氢原子,C 1 -C 10烷基,C 2 -C 20链烯基 取代或未取代的苯基,取代或未取代的C3-C10环烷基,取代或未取代的苯基(C1-C2)烷基或一个当量的阳离子; R2和R3可以相同或不同,表示氢原子,三(C1-C7)烃甲硅烷基或与羟基的氧原子一起形成缩醛键的基团; R4表示氢原子,甲基或乙烯基; R 5表示直链或支链C 3 -C 8烷基,直链或支链C 3 -C 8烯基,直链或支链C 2 -C 8炔基,可被取代的苯基,可被取代的苯氧基,C3 可以被取代的C 10环烷基,或可以被C 1 -C 6烷氧基取代的直链或支链C 1 -C 5烷基,可被取代的苯基,可被取代的苯氧基或C 3 -C 6烷氧基, 可被取代的C 10环烷基; X表示亚乙基,亚乙烯基或亚乙基; n表示0或1; 该表达式表示亚乙基或亚乙烯基,条件是当n是o且x是亚乙基时,R 5不是直链或支链C 3 -C 8烷基或可被取代的C 3 -C 10环烷基。 这些化合物特别可用于治疗和预防消化器官疾病如十二指肠溃疡或胃溃疡。
    • 8. 发明授权
    • Thiaprostaglandin E.sub.1 derivatives, process for production thereof,
and pharmaceutical use thereof
    • Thiaprostaglandin E1衍生物,其制备方法及其药物用途
    • US4466980A
    • 1984-08-21
    • US316902
    • 1981-10-30
    • Toshio TanakaTakeshi ToruTakeo ObaNoriaki OkamuraKenzo WatanabeKiyoshi BannaiAtsuo HazatoSeizi KurozumiFukuyoshi KamimotoAkira Ohtsu
    • Toshio TanakaTakeshi ToruTakeo ObaNoriaki OkamuraKenzo WatanabeKiyoshi BannaiAtsuo HazatoSeizi KurozumiFukuyoshi KamimotoAkira Ohtsu
    • C07C405/00C07D309/12C07C177/00A61K31/557
    • C07C405/0033C07D309/12
    • 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.
    • 选自式(I)的7-(或6-或4-)赖氨酸前列腺素E1衍生物的新化合物。 (I)其中A表示-CH 2 - 或,其中n为0,1或2,条件是三个只有一个A切割是R 1 -R 7,G如说明书中所定义, 所述thiaprostaglandin E1衍生物的15-差向异构体,所述thiaprostaglandin E1衍生物或它们的15-差向异构体的对映体,以及这些化合物的混合物。 7-硫代前列腺素E1衍生物和/或其旋光异构体可以通过2-有机-2-环戊烯酮(II)与有机铜 - 锂化合物(III)反应来制备共轭反应。 6-硫代前列腺素E1衍生物和/或其旋光异构体可以通过使α,β-不饱和酮(IV)和硫醇(V)进行迈克尔加成反应来制备。 并且,也可以通过从2-烯丙基取代的环戊酮(VI)和硫醇(VIII)的迈克尔加成反应制备4-硫代前列腺素衍生物和/或其旋光异构体。 式(I)化合物和/或其旋光异构体中的一些化合物((I)-1)可用于控制血管作用,例如心绞痛,血管舒张等。
    • 9. 发明授权
    • Process for producing 16-substituted prostaglandin es.
    • 生产16-取代的前列腺素的方法。
    • US4841091A
    • 1989-06-20
    • US913889
    • 1986-09-29
    • Toshio TanakaAtsuo HazatoSeizi KurozumiMasahiro Koga
    • Toshio TanakaAtsuo HazatoSeizi KurozumiMasahiro Koga
    • C07C405/00
    • C07C405/0033C07C405/00
    • A novel process for manufacturing 16-substituted .DELTA..sup.7 -prostaglandin Es, which include compounds expressed by the following formula (I), their enanantiomers, or their mixtures of arbitray mixing ratio, ##STR1## wherein R.sup.1 indicates COOR.sup.2, CH.sub.2 OR.sup.3, in which R.sup.2 indicates a hydrogen atom, a dubstituted or unsubstituted C.sub.1 -C.sub.10 alkyl group, a substituted or unsubstituted C.sub.3 -C.sub.10 cycloalkyl group, or a substituted or unsubstituted phenyl group, and R.sup.3 indicates a hydrogen atom, a tri(C.sub.1 -C.sub.7) hydrocarbon silyl group, a group which forms an acetal bond together with the oxygen atom of a hydroxyl group, or a C.sub.2 -C.sub.7 acyl group; R.sup.4 and R.sup.5 are identical or different, each representing a hydrogen atom, a tri(C.sub.1 -C.sub.7 ) hydrocarbon silyl group, or a group which forms an acetal bond together with the oxygen atom of a hydroxyl group; R.sup.6 indicates a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group, or a vinyl group; R.sup.7 indicates a linear or branched C.sub.3 -C.sub.8 alkyl group, an alkyenyl group, or an alkynyl group, which may contain an oxygen atom; a phenyl group, a phenoxy group, or a C.sub.3 -C.sub.10 cycloalkyl group, which may be substituted; or a linear or branched C.sub.1 -C.sub.5 alkyl group which is substituted by a C.sub.1 -C.sub.6 alkoxy group, a phenyl group a phenoxy group, or a C.sub.3 -C.sub.10 cycloalkyl group, which may be substituted; and Y indicates CH.sub.2 X or XCH.sub.2, in which X represents an ethylene group, a cis -or trans-vinylene group, or an ethynylene group.
    • PCT No.PCT / JP86 / 00034 Sec。 371日期1986年9月29日第 102(e)1986年9月29日PCT PCT公布1986年1月28日PCT公布。 出版物WO86 / 04330 日期:1986年7月31日。一种用于制备16取代的DELTA 7-前列腺素Es的新方法,其包括由下式(I)表示的化合物,其对映异构体或其混合比的混合物, 其中R1表示COOR2,CH2OR3,其中R2表示氢原子,取代或未取代的C1-C10烷基,取代或未取代的C3-C10环烷基或取代或未取代的苯基,R3表示氢原子, 三(C 1 -C 7)烃甲硅烷基,与羟基的氧原子一起形成缩醛键的基团或C 2 -C 7酰基; R4和R5相同或不同,各自表示氢原子,三(C1-C7)烃甲硅烷基,或与羟基的氧原子一起形成缩醛键的基团; R6表示氢原子,C1-C4烷基或乙烯基; R7表示可含有氧原子的直链或支链C 3 -C 8烷基,链烯基或炔基; 可被取代的苯基,苯氧基或C3-C10环烷基; 或被可被取代的C1-C6烷氧基,苯基苯氧基或C3-C10环烷基取代的直链或支链C1-C5烷基; Y表示CH2X或XCH2,其中X表示亚乙基,顺式或反式亚乙烯基或亚乙炔基。
    • 10. 发明授权
    • Process for producing 16-substituted prostaglandines
    • 生产16-取代的前列腺素的方法
    • US4921995A
    • 1990-05-01
    • US153881
    • 1988-02-09
    • Toshio TanakaAtsuo HazatoSeizi KurozumiMasahiro Koga
    • Toshio TanakaAtsuo HazatoSeizi KurozumiMasahiro Koga
    • C07C405/00
    • C07C405/0033C07C405/00
    • A novel process for manufacturing 16-substituted .DELTA..sup.7 -prostaglandin Es, which include compounds expressed by the following formula (I), their enanantiomers, or their mixtures of arbitrary mixing ratio, ##STR1## wherein R.sup.1 indicates COOR.sup.2, CH.sub.2 OR.sup.3, or COCH.sub.2 OR.sup.3, in which R.sup.2 indicates a hydrogen atom, a substituted or unsubstituted C.sub.1 -C.sub.10 alkyl group, a substituted or unsubstituted C.sub.3 -C.sub.10 cycloalkyl group, or a substituted or unsubstituted phenyl group, and R.sup.3 indicates a hydrogen atom, a tri(C.sub.1 -C.sub.7) hydrocarbon silyl group, a group which forms an acetal bond together with the oxygen atom of a hydroxyl group, or a C.sub.2 -C.sub.7 acyl group; R.sup.4 and R.sup.5 are identical or different, each representing a hydrogen atom, a tri(C.sub.1 -C.sub.7) hydrocarbon silyl group, or a group which forms an acetal bond together with the oxygen atom of a hydroxyl group; R.sup.6 indicates a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group, or a vinyl group; R.sup.7 indicates a linear or branched C.sub.3 -C.sub.8 alkyl group, an alkyenyl group, or an alkynyl group, which may contain an oxygen atom; a phenyl group, a phenoxy group, or a C.sub.3 - C.sub.10 cycloalkyl group, which may be substituted; or a linear or branched C.sub.1 -C.sub.5 alkyl group which is substituted by a C.sub.1 -C.sub.6 alkoxy group, a phenyl group, a phenoxy group, or a C.sub.3 -C.sub.10 cycloalkyl group, which may be substituted; and Y indicates CH.sub.2 X or XCH.sub.2, in which X represents an ethylene group, a cis -or trans-vinylene group, or an ethynylene group.