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    • 2. 发明授权
    • Fluorinated amino-butyric acid and diaminobutane derivatives
    • 氟化氨基丁酸和二氨基丁烷衍生物
    • US4418077A
    • 1983-11-29
    • US295060
    • 1981-08-21
    • Philippe BeyFritz GerhartMichel JungDaniel Schirlin
    • Philippe BeyFritz GerhartMichel JungDaniel Schirlin
    • A61K31/13A61K31/135A61K31/16A61K31/165A61K31/195A61K31/22A61P25/00C07C211/15C07C229/20C07C233/36C07C233/47C07C237/06C07C271/22C07C273/10C07D209/48C07C87/22C07C87/28C07C101/24
    • C07D209/48C07C271/22
    • Fluorinated aminobutyric acid and diaminobutane compounds in vivo are inhibitors of gamma-aminobutyric acid transaminase and have the following formula: ##STR1## wherein: Y represents hydrogen or fluorine;Z represents --CH.sub.2 NR.sub.1 R.sub.2, where R.sub.1 and R.sub.2 are as defined below, or --COR.sub.3 where R.sub.3 is as defined below;R.sub.a represents hydrogen or R.sub.4, where R.sub.4 is as defined below;R.sub.1 represents hydrogen, C.sub.1 -C.sub.6 alkyl or phenyl-(C.sub.1 -C.sub.4 alkyl);R.sub.2 represents hydrogen, C.sub.1 -C.sub.6 alkyl, phenyl-(C.sub.1 -C.sub.4 alkyl) or, when R.sub.a is hydrogen, R.sub.4, where R.sub.4 is as defined below;R.sub.3 represents hydroxy, or when R.sub.a is hydrogen, C.sub.1 -C.sub.8 alkoxy, --NR.sub.5 R.sub.6, where R.sub.5 and R.sub.6 are as defined below, or an aminocarboxylic acid residue derived by removal of an hydrogen atom from the amino moiety of an L-aminocarboxylic acid;each R.sub.4, independently, represents C.sub.2 -C.sub.5 alkylcarbonyl, phenylcarbonyl, phenyl-(C.sub.1 -C.sub.4 alkyl)-carbonyl, or an aminocarboxylic acid residue derived by removal of an hydroxy group from the carboxy moiety of an L-aminocarboxylic acid;R.sub.5 and R.sub.6, independently, represent hydrogen or C.sub.1 -C.sub.4 alkyl; andP represents 1 or 2.
    • 氟化氨基丁酸和二氨基丁烷化合物在体内是γ-氨基丁酸转氨酶的抑制剂,具有下式:其中:Y代表氢或氟; Z表示-CH2NR1R2,其中R1和R2如下所定义,或-COR 3,其中R3如下所定义; R a表示氢或R 4,其中R 4如下所定义; R1代表氢,C1-C6烷基或苯基 - (C1-C4烷基); R 2表示氢,C 1 -C 6烷基,苯基 - (C 1 -C 4烷基)或当R a是氢时,R 4,其中R 4如下所定义; R3表示羟基,或当R a为氢时,C 1 -C 8烷氧基,-NR 5 R 6(其中R 5和R 6如下所定义)或通过从L-氨基羧酸的氨基部分除去氢原子得到的氨基羧酸残基; 每个R 4独立地表示C 2 -C 5烷基羰基,苯基羰基,苯基 - (C 1 -C 4烷基) - 羰基或通过从L-氨基羧酸的羧基部分除去羟基而衍生的氨基羧酸残基; R5和R6独立地表示氢或C1-C4烷基; P表示1或2。
    • 3. 发明授权
    • Fluorinated pentene diamine derivatives
    • 氟化戊烯二胺衍生物
    • US4439619A
    • 1984-03-27
    • US295152
    • 1981-08-21
    • Philippe BeyFritz GerhartMichel Jung
    • Philippe BeyFritz GerhartMichel Jung
    • A61K31/57C07C43/17C07C233/00C07C233/34C07C271/20C07D209/48C07D487/18C07J5/00C07C101/24C07C87/26
    • C07D209/48C07C255/00C07C271/20C07C43/17
    • Fluorinated alkenylene diamine compounds are inhibitors of ornithine decarboxylase enzyme in vivo and have the following formula: ##STR1## wherein: R.sub.a represents hydrogen or R.sub.2, where R.sub.2 is as defined below;R.sub.b represents hydrogen or, when R.sub.a is hydrogen, R.sub.2, where R.sub.2 is as defined below;R.sub.c represents hydrogen or --COR.sub.3, where R.sub.3 is as defined below;R.sub.1 represents hydrogen or C.sub.1 --C.sub.6 alkyl;each R.sub.2, independently, represents C.sub.2 -C.sub.5 alkylcarbonyl, phenylcarbonyl, phenyl-(C.sub.1 -C.sub.4 alkyl) carbonyl, or an aminocarboxylic acid residue derived by removal of an hydroxy group from a carboxy moiety of an L-aminocarboxylic acid;R.sub.3 represents hydroxy, or, when R.sub.a and R.sub.b are both hydrogen, C.sub.1 -C.sub.8 alkoxy, --NR.sub.4 R.sub.5, where R.sub.4 and R.sub.5 are as defined below, or an aminocarboxylic acid residue derived by removal of an hydrogen atom from the amino moiety of an L-aminocarboxylic acid;R.sub.4 and R.sub.5, independently, represent hydrogen or C.sub.1 -C.sub.4 alkyl; andp represents 1 or 2.
    • 氟化亚烯基二胺化合物是体内鸟氨酸脱羧酶的抑制剂,具有下式:其中:R a表示氢或R 2,其中R 2如下所定义; Rb表示氢,或当R a为氢时,R 2,其中R 2如下所定义; R c表示氢或-COR 3,其中R 3如下所定义; R1代表氢或C1-C6烷基; 每个R 2独立地表示C 2 -C 5烷基羰基,苯基羰基,苯基 - (C 1 -C 4烷基)羰基或通过从L-氨基羧酸的羧基部分除去羟基衍生的氨基羧酸残基; R3表示羟基,或者当R a和R b均为氢时,C 1 -C 8烷氧基,-NR 4 R 5(其中R 4和R 5如下所定义)或通过从L的氨基部分除去氢原子得到的氨基羧酸残基 - 氨基羧酸; R 4和R 5独立地表示氢或C 1 -C 4烷基; p表示1或2。
    • 6. 发明授权
    • Method of treating psoriasis
    • 治疗牛皮癣的方法
    • US4496588A
    • 1985-01-29
    • US487243
    • 1983-04-28
    • Philippe BeyMichel Jung
    • Philippe BeyMichel Jung
    • A61K31/16A61K31/195A61K38/00C07D211/74C07D211/76C07D223/08C07H19/02C07H19/16C07K5/06
    • C07H19/16A61K31/16A61K31/195C07D211/74C07D211/76C07D223/08C07H19/02C07K5/06191A61K38/00Y10S514/863
    • A novel method of treating psoriasis which comprises administering a halomethyl derivative of .alpha.-amino acids of the following general structure: ##STR1## wherein Y is FCH.sub.2 --, F.sub.2 CH--, F.sub.3 C--, ClCH.sub.2 --, Cl.sub.2 CH--; Z is .gamma.-guanidinopropyl or R.sub.a HN(CH.sub.2).sub.n -- wherein n is the integer 3 or 4; each of R.sub.a and R.sub.b can be the same or different and is hydrogen, alkylcarbonyl wherein the alkyl moiety has from 1 to 4 carbon atoms and is straight or branched, alkoxycarbonyl wherein the alkoxy moiety has from 1 to 4 carbon atoms and is straight or branched, or ##STR2## wherein R.sub.2 is hydrogen, a straight or branched lower alkyl group of from 1 to 4 carbon atoms, benzyl or p-hydroxybenzyl; R.sub.1 is hydroxy; a straight or branched alkoxy group of from 1 to 8 carbon atoms, --NR.sub.4 R.sub.5 wherein each of R.sub.4 and R.sub.5 is hydrogen or a lower alkyl group of from 1 to 4 carbon atoms, or ##STR3## wherein R.sub.3 is hydrogen, a straight or branched lower alkyl group of from 1 to 4 carbon atoms, benzyl or p-hydroxybenzyl; and the lactams thereof when Z is R.sub.a HN(CH.sub.2).sub.n -- and each of R.sub.a and R.sub.b is hydrogen; with the proviso that when Z is .gamma.-guanidinopropyl Y is FCH.sub.2 --, F.sub.2 CH-- or F.sub.3 C-- and R.sub.1 is hydroxy; and pharmaceutically acceptable salts and individual optical isomers thereof.
    • 一种治疗牛皮癣的新方法,其包括施用以下通用结构的α-氨基酸的卤代甲基衍生物:其中Y是FCH 2 - ,F 2 CH-,F 3 C - ,ClCH 2 - ,Cl 2 CH-; Z是γ-胍基丙基或RaHN(CH2)n-,其中n是3或4的整数; R a和R b中的每一个可以相同或不同,并且是氢,烷基部分具有1至4个碳原子并且是直链或支链的烷氧基羰基,其中烷氧基部分具有1至4个碳原子并且是直链或支链 或者其中R 2是氢,1至4个碳原子的直链或支链低级烷基,苄基或对羟基苄基; R1是羟基; 1至8个碳原子的直链或支链烷氧基,-NR4R5,其中R4和R5各自为氢或1至4个碳原子的低级烷基,或者其中R3为氢,直链或支链的 1至4个碳原子的低级烷基,苄基或对羟基苄基; 当Z为RaHN(CH2)n-且其各自的R a和R b为氢时,其内酰胺; 条件是当Z是γ-胍基丙基时,Y是FCH 2 - ,F 2 CH-或F 3 C-,R 1是羟基; 及其药学上可接受的盐和单独的光学异构体。
    • 7. 发明授权
    • Alpha-halomethyl derivatives of amines
    • 胺的α-卤代甲基衍生物
    • US4134918A
    • 1979-01-16
    • US830998
    • 1977-09-06
    • Philippe BeyMichel Jung
    • Philippe BeyMichel Jung
    • A61K31/16A61K31/13A61K31/165A61K31/325A61K31/52A61P43/00C07C67/00C07C209/00C07C209/62C07C211/15C07C231/00C07C233/36C07C239/00C07C279/04C07C313/00C07C323/41C07C323/44C07D209/48C07H19/16C07C87/22C01B25/26C07C69/02C07C103/10
    • C07D209/48C07H19/16
    • Novel halomethyl derivatives of amines of the following general structure: ##STR1## WHEREIN Y is FCH.sub.2 --, F.sub.2 CH-- or F.sub.3 C--; Z is .beta.-methylthioethyl, .beta.-benzylthioethyl, S-(5'-desoxyadenosin-5'-yl)-S-methylthioethyl, .gamma.-guanidinopropyl, or ##STR2## WHEREIN N IS 2 OR 3 AND R.sub.1 is hydrogen or lower alkyl of from 1 to 4 carbon atoms with the proviso that when R.sub.1 is other than hydrogen, n is 2; and each of R.sub.a and R.sub.b is hydrogen, alkylcarbonyl wherein the alkyl moiety has from 1 to 4 carbon atoms and is straight or branched, alkoxycarbonyl wherein the alkoxy moiety has from 1 to 4 carbon atoms and is straight or branched, or ##STR3## wherein R.sub.2 is hydrogen, a straight or branched lower alkyl group of from 1 to 4 carbon atoms, benzyl or p-hydroxybenzyl; with the provisos that when Z is .beta.-benzylthioethyl or S-(5'-desoxyadenosin-5'-yl)-S-methylthioethyl, R.sub.b is hydrogen, when Z is .beta.-methylthioethyl, Y is other than F.sub.3 C--, and when Z is ##STR4## EACH OF R.sub.a and R.sub.b can be the same or different; and pharmaceutically acceptable salts and individual optical isomers thereof.
    • 胺的新型卤代甲基衍生物具有以下通用结构:其中Y是FCH 2 - ,F 2 CH-或F 3 C-; Z是β-甲硫基乙基,β-苄硫基乙基,S-(5'-脱氧腺苷-5'-基)-S-甲硫基乙基,γ-胍基丙基或其中R是氢或低级烷基 1至4个碳原子,条件是当R1不是氢时,n是2; 并且R a和R b中的每一个是氢,其中烷基部分具有1至4个碳原子并且是直链或支链的烷氧基羰基,其中烷氧基部分具有1至4个碳原子并且是直链或支链的,或其中 R2是氢,1至4个碳原子的直链或支链低级烷基,苄基或对羟基苄基; 条件是当Z是β-苄硫基乙基或S-(5'-脱氧腺苷-5'-基)-S-甲硫基乙基时,R b是氢,当Z是β-甲硫基乙基时,Y不是F3C-,当Z Ra和Rb可以相同或不同; 及其药学上可接受的盐和单独的光学异构体。
    • 10. 发明授权
    • .alpha.-Halomethyl derivatives of .alpha.-amino acids
    • α-氨基酸的α-甲基甲基衍生物
    • US4560795A
    • 1985-12-24
    • US577116
    • 1984-02-06
    • Philippe BeyMichel Jung
    • Philippe BeyMichel Jung
    • A61K31/16A61K31/195A61K38/00C07D211/74C07D211/76C07D223/08C07H19/02C07H19/16C07K5/06C07C101/24
    • C07H19/16A61K31/16A61K31/195C07D211/74C07D211/76C07D223/08C07H19/02C07K5/06191A61K38/00
    • Novel halomethyl derivatives of .alpha.-amino acids of the following general structure: ##STR1## wherein Y is F.sub.2 CH--, F.sub.3 C--, Cl.sub.2 CH--; Z is .beta.-methylthioethyl, .beta.-thioethyl, .beta.-benzylthioethyl; S-(5'-desoxyadenosin-5'-yl)-S-methylthioethyl, .gamma.-guanidinopropyl, R.sub.a HN(CH.sub.2).sub.n -- wherein n is the integer 3 or 4 or ##STR2## wherein Y.sub.2 is F.sub.2 CH--, or F.sub.3 C--; each of R.sub.a and R.sub.b can be the same or different and is hydrogen, alkylcarbonyl wherein the alkyl moiety has from 1 to 4 carbon atoms and is straight or branched, alkoxycarbonyl wherein the alkoxy moiety has from 1 to 4 carbon atoms and is straight or branched, or ##STR3## wherein R.sub.2 is hydrogen, a straight or branched lower alkyl group of from 1 to 4 carbon atoms, benzyl or p-hydroxybenzyl; R.sub.1 is hydroxy, a straight or branched alkoxy group of from 1 to 8 carbon atoms, --NR.sub.4 R.sub.5 wherein each of R.sub.4 and R.sub.5 is hydrogen or a lower alkyl group of from 1 to 4 carbon atoms, or ##STR4## wherein R.sub.3 is hydrogen, a straight or branched lower alkyl group of from 1 to 4 carbon atoms, benzyl or p-hydroxybenzyl; and the lactams thereof when Z is R.sub.a HN(CH.sub.2).sub.n -- and each of R.sub.a and R.sub.b is hydrogen; with the provisos that when Z is .gamma.-guanidinopropyl or .beta.-methylthioethyl, Y is FCH.sub.2 --, F.sub.2 CH-- or F.sub.3 C--; when Z is .gamma.-guanidinopropyl, R.sub.1 is hydroxy; and when Z is .beta.-thioethyl, .beta.-benzylthioethyl, S-(5'-desoxyadenosin-5'-yl)-S-methylthioethyl or ##STR5## Y and Y.sub.2 are FCH.sub.2 --, F.sub.2 CH--, or F.sub.3 C-- and are the same, each of R.sub.a and R.sub.b is hydrogen and R.sub.1 is hydroxy; and pharmaceutically acceptable salts and individual optical isomers thereof.
    • 以下通式结构的α-氨基酸的新型卤代甲基衍生物:其中Y为F 2 CH - ,F 3 C - ,Cl 2 CH-; Z是β-甲硫基乙基,β-硫乙基,β-苄硫基乙基; S-(5'-脱氧腺苷酸-5'-基)-S-甲硫基乙基,γ-胍基丙基,RaHN(CH2)n-,其中n为整数3或4,或其中Y2为F2CH-或F3C-; R a和R b中的每一个可以相同或不同,并且是氢,烷基部分具有1至4个碳原子并且是直链或支链的烷氧基羰基,其中烷氧基部分具有1至4个碳原子并且是直链或支链 或者其中R 2是氢,1至4个碳原子的直链或支链低级烷基,苄基或对羟基苄基; R1是羟基,1至8个碳原子的直链或支链烷氧基,-NR4R5,其中R4和R5各自是氢或1-4个碳原子的低级烷基,或者其中R3是氢, 1至4个碳原子的直链或支链低级烷基,苄基或对羟基苄基; 当Z为RaHN(CH2)n-且其各自的R a和R b为氢时,其内酰胺; 条件是当Z是γ-胍基丙基或β-甲硫基乙基时,Y是FCH 2 - ,F 2 CH-或F 3 C-; 当Z是γ-胍基丙基时,R 1是羟基; 当Z是β-硫代乙基时,β-苄基硫代乙基,S-(5'-脱氧腺苷-5'-基)-S-甲硫基乙基Y和Y 2是FCH 2 - , - - - R a和R b各自为氢,R 1为羟基; 及其药学上可接受的盐和单独的光学异构体。