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    • 3. 发明授权
    • 6,9-Nitrilo-prostaglandin analogues
    • 6,9-Nitrilo-prostaglandin类似物
    • US4313954A
    • 1982-02-02
    • US122704
    • 1980-02-19
    • Hirohisa WakatsukaMasaki HayashiYoshitaka Konishi
    • Hirohisa WakatsukaMasaki HayashiYoshitaka Konishi
    • A61K31/557A61P7/02A61P43/00C07C405/00C07D209/52A61K31/40
    • C07C405/0041C07C405/00C07D209/52
    • Prostaglandin I.sub.2 analogues of the general formula ##STR1## [wherein R.sup.1 represents a hydrogen atom, an alkyl group containing from 1 to 12 carbon atoms, an aralkyl group containing from 7 to 13 carbon atoms, a cycloalkyl group containing from 4 to 7 carbon atoms unsubstituted or substituted by at least one alkyl group containing from 1 to 4 carbon atoms, a phenyl group unsubstituted or substituted by at least one halogen atom, trifluoromethyl or phenyl group, or by at least one alkyl, alkoxy or alkylthio group containing from 1 to 4 carbon atoms, or represents a group --C.sub.m H.sub.2m COOR.sup.6, --C.sub.n H.sub.2n OR.sup.7 or ##STR2## in which m represents an integer of 1 to 12, n represents an integer of 2 to 12, R.sup.6, R.sup.8 and R.sup.9, which may be the same or different, each represent an alkyl group containing from 1 to 4 carbon atoms, and R.sup.7 represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms, R.sup.2 represents a hydrogen atom or a methyl or ethyl group, R.sup.3 represents an alkyl group containing from 1 to 4 carbon atoms, R.sup.4 represents a hydrogen atom, or an alkyl group containing from 1 to 4 carbon atoms, R.sup.5 represents an alkyl group containing from 1 to 10 carbon atoms, Y represents ethylene or trans-vinylene, the hydroxy group attached to the C-11 carbon atom is in .alpha.-configuration, and the wavy line attached to the C-15 carbon atom is in .alpha.- or .beta.-configuration or a mixture thereof] and non-toxic acid addition salts thereof and, when R.sup.1 represents a hydrogen atom, non-toxic salts thereof are new compounds possessing pharmacological properties typical of the prostaglandins.
    • 具有通式的前列腺素I2类似物[其中R1表示氢原子,含有1至12个碳原子的烷基,含有7至13个碳原子的芳烷基,含有4至7个碳原子的环烷基 未取代或被至少一个含有1至4个碳原子的烷基取代的苯基,未被取代或被至少一个卤素原子取代的苯基,三氟甲基或苯基,或至少一个含有1至4个碳原子的烷基,烷氧基或烷硫基 4个碳原子,或表示基团-C m H 2 mCOOR 6,-C n H 2n OR 7或其中m表示1至12的整数,n表示2至12的整数,R 6,R 8和R 9可以相同或不同 各自表示含有1至4个碳原子的烷基,R 7表示氢原子或含有1至4个碳原子的烷基,R 2表示氢原子或甲基或乙基,R 3表示含有 从1 至4个碳原子,R 4表示氢原子或含有1至4个碳原子的烷基,R 5表示含有1至10个碳原子的烷基,Y表示亚乙基或反式亚乙烯基, C-11碳原子为α-构型,连接至C-15碳原子的波浪线为α-或β-构型或其混合物)及其无毒的酸加成盐,当R1表示 氢原子,其无毒盐是具有典型的前列腺素的药理学性质的新化合物。
    • 4. 发明授权
    • Trans-.DELTA..sup.2 -prostaglandins
    • Trans- {66 {hu 2 {b-前列腺素
    • US3931296A
    • 1976-01-06
    • US427403
    • 1973-12-21
    • Masaki HayashiHirohisa WakatsukaSeiji Kori
    • Masaki HayashiHirohisa WakatsukaSeiji Kori
    • C07C405/00C07D307/935C07D309/12C07F9/40C07F9/54C07C61/38C07C69/74
    • C07D307/935C07C405/00C07C405/0025C07D309/12C07F9/4006C07F9/5407Y10S514/927
    • New process for the preparation of trans-.DELTA..sup.2 -prostaglandins of the formula ##SPC1##(wherein A represents a grouping of the PGE, PGF or PGA type, X represents --CH.sub.2 CH.sub.2 -- or trans --CH=CH--, R.sub.1 represents an alkyl radical of 1 to 10 carbon atoms or an alkyl radical of 1 to 6 carbon atoms carrying a phenyl substituent or a cycloalkyl substituent of 5 to 7 carbon atoms, R.sub.2 represents a hydrogen atom or an alkyl radical of 1 to 4 carbon atoms) and alkyl esters thereof having 1 to 10 carbon atoms in the chain, which comprises reacting a cyclopentane derivative of the formula: ##SPC2##(where R.sub.3 represents a 2-tetrahydropyranyl group unsubstituted or substituted by at least one alkyl radical, or a 1-ethoxyethyl group) with an alkyl phosphonate of the general formula: ##EQU1## (wherein R.sub.4 represents a methyl or ethyl radical, and R.sub.5 represents an alkyl radical of 1 to 10 carbon atoms), optionally hydrolyzing the resulting trans-.DELTA..sup.2 -prostaglandin ester of the general formula: ##SPC3##To the corresponding acid, optionally converting the 9.alpha.-hydroxy radical in the ester or acid product to an oxo group, and hydrolyzing the tetrahydropyranyloxy or ethoxyethoxy groups in the resulting trans-.DELTA..sup.2 -prostaglandin compound of the formula: ##SPC4##(wherein R.sub.6 represents a hydrogen atom or an alkyl radical of 1 to 10 carbon atoms, Z represents ##EQU2## or C=O) to hydroxy radicals to obtain a trans-.DELTA..sup.2 -PGF or trans-.DELTA..sup.2 -PGE compound of the formula: ##SPC5##And, if desired, converting the PGE alicyclic ring (Z represents C=O) into that of a PGA compound.The trans-.DELTA..sup.2 -prostaglandin products, which are new compounds except for trans-.DELTA..sup.2 -PGE.sub.1, possess typical pharmacological properties of the `natural` prostaglandins.
    • 用于制备下式的转DELTA 2-前列腺素的新方法(WHEREIN A代表PGE,PGF或PGA类型的一组,X表示-CH 2 CH 2 - 或反-CH = CH-,R 1表示1的烷基 至10个碳原子或1至6个碳原子的烷基,带有苯基取代基或5至7个碳原子的环烷基取代基,R2表示氢原子或1至4个碳原子的烷基)及其烷基酯,其具有 1至10个碳原子的链,其包括使下式的环戊烷衍生物:
    • 7. 发明授权
    • Prostaglandin 12 analogues and their pharmaceutical compositions
    • 前列腺素12类似物及其药物组合物
    • US4399147A
    • 1983-08-16
    • US872635
    • 1978-01-26
    • Masaki HayashiYoshinobu AraiYoshitaka KonishiKatsuichi ShimojiShuichi OhuchidaHirohisa WakatsukaHiroyuki Ito
    • Masaki HayashiYoshinobu AraiYoshitaka KonishiKatsuichi ShimojiShuichi OhuchidaHirohisa WakatsukaHiroyuki Ito
    • C07D307/935A61K31/34A61K31/343A61P43/00C07C405/00C07D307/937A61K31/557
    • C07D307/937C07C405/00
    • Prostaglandin I.sub.2 analogues of the formula: ##STR1## [wherein X represents trans-vinylene or an ethylene group unsubstituted or substituted by a bromine atom at the C-5 position, Y represents trans-vinylene or ethylene, R.sup.1 represents hydrogen or an alkyl group containing from 1 to 12 carbon atoms, R.sup.2 represents hydrogen or methyl or ethyl, R.sup.3 represents a single bond or an alkylene group containing from 1 to 4 carbon atoms, R.sup.4 represents hydrogen, an alkyl group containing from 1 to 8 carbon atoms, a cycloalkyl group containing from 4 to 7 carbon atoms unsubstituted or substituted by at least one alkyl group containing from 1 to 8 carbon atoms, or a phenyl or phenoxy group unsubstituted or carrying at least one substituent selected from halogen atoms, the trifluoromethyl group and alkyl groups containing from 1 to 3 carbon atoms, and the wavy line attached to the carbon atoms in positions 6, 11 and 15 depicted in the formula represents .alpha.- or .beta.-configuration or mixtures thereof] are new compounds possessing pharmacological properties typical of prostaglandins, for example PGI.sub.2, and are more stable than PGI.sub.2.
    • 前列腺素I2类似物,具有下式:其中X表示反式亚乙烯基或未被取代或被C-5位上的溴原子取代的亚乙基,Y表示反式亚乙烯基或亚乙基,R 1表示氢或烷基 含有1至12个碳原子,R 2表示氢或甲基或乙基,R 3表示单键或含有1至4个碳原子的亚烷基,R 4表示氢,含有1至8个碳原子的烷基,环烷基 含有未取代或被至少一个含有1至8个碳原子的烷基取代的4至7个碳原子的基团,或未取代或携带至少一个选自卤素原子的取代基的苯基或苯氧基,三氟甲基和含有 1至3个碳原子,并且连接在式中描述的6,11和15位的碳原子上的波浪线代表α-或β-构型或其混合物] 是具有典型的前列腺素的药理学性质的新化合物,例如PGI 2,并且比PGI2更稳定。
    • 9. 发明授权
    • Prostacyclin analogues
    • US4367237A
    • 1983-01-04
    • US097675
    • 1979-11-27
    • Hirohisa WakatsukaKatsuichi ShimojiSadahiko IguchiYoshitaka KonishiHisashi SugaYasuyuki MiyataYoichi IguchiHajimu MiyakeMasaki Hayashi
    • Hirohisa WakatsukaKatsuichi ShimojiSadahiko IguchiYoshitaka KonishiHisashi SugaYasuyuki MiyataYoichi IguchiHajimu MiyakeMasaki Hayashi
    • C07C405/00C07D333/78C07D335/04A61K31/38
    • C07C405/0033C07C405/00C07D333/78C07D335/04
    • Prostaglandin analogues of the general formula: ##STR1## [wherein the ring A represents: ##STR2## the ring B represents: ##STR3## (wherein R.sup.6 represents hydrogen, methyl or ethyl, and r is zero, one or two), Y represents ethylene, cis- or trans-vinylene or ethynylene, Z represents a grouping of the formula: --(CH.sub.2).sub.m --, --(CH.sub.2).sub.3 --CHR.sup.7 --, --(CH.sub.2).sub.2 --CHR.sup.7 --CH.sub.2 --, --CH.sub.2 --CHR.sup.7 --(CH.sub.2).sub.2 --, --CHR.sup.7 --(CH.sub.2).sub.3 --, or trans--(CH.sub.2).sub.2 --CH.dbd.CH-- (wherein m is 3, 4 or 5, and R.sup.7 represents methyl or ethyl), R.sup.1 represents a grouping of the formula: --COOR.sup.8, ##STR4## or --CH.sub.2 OR.sup.11 (wherein R.sup.8 represents hydrogen, alkyl, aralkyl, cycloalkyl which is unsubstituted or substituted by at least one alkyl group, or R.sup.8 represents phenyl which is unsubstituted or substituted by halogen, trifluoromethyl, alkyl, alkoxy, alkylthio or phenyl, or represents naphthyl, 2,3- or 1,3-dihydroxypropyl, 2,3- or 1,3-bisalkanoyloxypropyl, a grouping of the formula: -D.sub.1 --COOR.sup.12, ##STR5## -D.sub.2 -R.sup.15 or -D.sub.3 -R.sup.16, wherein D.sub.1 represents alkylene, D.sub.2 represents alkylene, D.sub.3 represents a single bond or alkylene, R.sup.12, R.sup.13 and R.sup.14, each represent alkyl, R.sup.15 represents hydroxy, alkoxy or alkylthio and R.sup.16 represents a heterocyclic ring, or R.sup.8 represents a grouping of the formula: ##STR6## R.sup.9 and R.sup.10, each represent hydrogen, alkyl, alkylsulphonyl, alkanoyl or ##STR7## represents a heterocyclic ring, and R.sup.11 represents hydrogen or alkanoyl, R.sup.2 represents hydrogen, methyl or ethyl, R.sup.3 represents a single bond or alkylene, R.sup.4 represents hydrogen, alkyl, alkoxy, cycloalkyl or cycloalkyloxy unsubstituted or substituted by alkyl, or represents phenyl or phenoxy unsubstituted or substituted by halogen, trifluoromethyl or alkyl with the proviso that, when R.sup.3 represents a single bond, R.sup.4 does not represent alkoxy, cycloalkyloxy or phenoxy, R.sup.5 represents hydrogen, methyl or ethyl and with the proviso that, when one of the groups R.sup.5, R.sup.6 and R.sup.7 represents methyl or ethyl the other two groups are hydrogen atoms] and cyclodextrin clathrates, non-toxic salts and non-toxic acid addition salts thereof, possess selective strong stimulatory activity on uterine contraction in female mammals.