公开(公告)号：US5451604A

公开(公告)日：1995-09-19

申请号：US97809

申请日：1993-07-26

申请人： Richard A. Mueller ,  Thomas E. Barta ,  John P. McKearn ,  Susan A. Gregory ,  Richard A. Partis ,  Francis J. Koszyk

发明人： Richard A. Mueller ,  Thomas E. Barta ,  John P. McKearn ,  Susan A. Gregory ,  Richard A. Partis ,  Francis J. Koszyk

IPC分类号： C07C255/42 ,  A61K31/275 ,  C07C247/06 ,  C07C255/35

CPC分类号： C07C255/42 ,  C07C2101/10

摘要： A class of halogenated phenylacetonitrile alkylaminoalkylphenyl compounds having immunosuppressive properties is described. Compounds of this class would be useful in reducing recipient rejection of transplanted organs and for treatment of autoimmune or inflammatory diseases. Compounds of particular interest are of the formula ##STR1## wherein m is a number selected from three to five, inclusive; wherein n one or two; wherein R.sup.1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, iso-butyl, n-pentyl, isopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, benzyl and phenethyl; wherein R.sup.2 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, iso-butyl, n-pentyl, isopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, benzyl and phenethyl; wherein each of R.sup.3 through R.sup.7 is selected from hydrido, fluoro, chloro, bromo, azide, trifluoromethyl, difluorochloromethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl and 2,2,2,3-tetrafluoropropyl; with the proviso that at least one of R.sup.3 through R.sup.7 is selected from fluoro and trifluoromethyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

摘要翻译： 描述了一类具有免疫抑制特性的卤代苯基乙腈烷基氨基烷基苯基化合物。 该类化合物可用于减少移植器官的受体排斥和治疗自身免疫性或炎性疾病。 特别感兴趣的化合物具有下式：其中m是选自三至五的数字，包括端值; 其中n个或两个; 其中R1选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，叔丁基，异丁基，正戊基，异戊基，环丙基，环丁基，环戊基，环己基，环丙基甲基，环丁基甲基，环戊基甲基 ，环己基甲基，苄基和苯乙基; 其中R2选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，叔丁基，异丁基，正戊基，异戊基，环丙基，环丁基，环戊基，环己基，环丙基甲基，环丁基甲基，环戊基甲基 ，环己基甲基，苄基和苯乙基; 其中R3至R7各自选自氢，氟，氯，溴，叠氮化物，三氟甲基，二氟氯甲基，1,1-二氟乙基，2,2,2-三氟乙基，全氟乙基和2,2,2,3-四氟丙基; 条件是R3至R7中的至少一个选自氟和三氟甲基; 或其互变异构体或其药学上可接受的盐。

公开(公告)号：US5622972A

公开(公告)日：1997-04-22

申请号：US585603

申请日：1996-01-26

申请人： Martin L. Bryant ,  Francis J. Koszyk ,  Richard A. Mueller ,  Richard A. Partis

发明人： Martin L. Bryant ,  Francis J. Koszyk ,  Richard A. Mueller ,  Richard A. Partis

IPC分类号： A61K31/445

CPC分类号： A61K31/445

摘要： A method is provided for treating a mammal infected with respiratory syncytial virus (RSV) comprising administering to the mammal an RSV inhibitory effective amount of a compound or its pharmaceutically acceptable salt of the formula ##STR1## wherein R.sup.1 is alkyl, aralkyl, aroyl or acyl and R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are H or acyl.

摘要翻译： 提供了一种治疗感染呼吸道合胞病毒（RSV）的哺乳动物的方法，包括向哺乳动物施用RSV抑制有效量的下式化合物或其药学上可接受的盐，其中R 1是烷基，芳烷基，芳酰基或酰基 R2，R3，R4和R5是H或酰基。

公开(公告)号：US5411970A

公开(公告)日：1995-05-02

申请号：US170593

申请日：1993-12-21

申请人： Richard A. Partis ,  Francis J. Koszyk ,  Richard A. Mueller

发明人： Richard A. Partis ,  Francis J. Koszyk ,  Richard A. Mueller

IPC分类号： C07D211/46 ,  C07D401/06 ,  C07D491/04 ,  A61K31/445

CPC分类号： C07D401/06 ,  C07D211/46 ,  C07D491/04

摘要： A method of inhibiting lentivirus is disclosed which comprises mammalian host susceptible to said lentivirus with a virally inhibitory effective amount of an O-acylated derivative of 1,5-dideoxy-1,5-imino-D-glucitol and their N-alkyl, N-acyl and N-aroyl derivatives in which from one to four of the free hydroxyl groups are O-acylated with carboxylic alkanoyl radicals selected from the group consisting of .omega.,.omega.,.omega.-trifluoroalkanoyl having from three to eight carbon atoms, carboxylic cycloalkanoyl groups having from four to eight carbon atoms and carboxylic acyclic alkanoyl groups having from two to ten carbon atoms, wherein the N-aroyl groups contain from 7 to 14 carbon atoms, the N-acyl groups contain from 4 to 8 carbon atoms and the N-alkyl groups contain from 1 to 14 carbon atoms.

摘要翻译： 公开了一种抑制慢病毒的方法，其包括对所述慢病毒敏感的哺乳动物宿主，其具有病毒抑制有效量的1,5-二脱氧-1,5-亚氨基-D-葡萄糖醇的O-酰化衍生物及其N-烷基，N 酰基和N-芳酰基衍生物，其中1至4个游离羟基与选自具有3至8个碳原子的ω，ω，ω-三氟烷酰基的羧基烷酰基进行O-酰化，羧基环烷酰基 具有4至8个碳原子和具有2至10个碳原子的羧酸非环烷酰基，其中N-芳酰基含有7至14个碳原子，N-酰基含有4至8个碳原子， 烷基含有1至14个碳原子。

公开(公告)号：US4876268A

公开(公告)日：1989-10-24

申请号：US266718

申请日：1988-11-03

申请人： Francis J. Koszyk ,  Richard A. Partis ,  Richard A. Mueller

发明人： Francis J. Koszyk ,  Richard A. Partis ,  Richard A. Mueller

IPC分类号： C07D207/12

CPC分类号： C07D207/12

摘要： Acylated derivatives of 1,4-dideoxy-1,4-imino-L-arabinitol and their N-alkyl and N-hydroxyalkyl derivatives in which all the free hydroxyl groups are acylated with acyl groups having from one to six carbon atoms and in which the N-alkyl substituents in the N-alkyl and N-hydroxyalkyl derivatives contain from one to fourteen carbon atoms are disclosed.

摘要翻译： 1,4-二脱氧-1,4-亚氨基-L-阿拉伯糖醇及其N-烷基和N-羟基烷基衍生物的酰化衍生物，其中所有游离羟基用具有1至6个碳原子的酰基进行酰化，其中 公开了N-烷基和N-羟烷基衍生物中的N-烷基取代基含有1-14个碳原子。

公开(公告)号：US5476944A

公开(公告)日：1995-12-19

申请号：US245780

申请日：1994-05-19

申请人： Richard A. Partis ,  Richard A. Mueller ,  Francis J. Koszyk ,  Richard M. Weier

发明人： Richard A. Partis ,  Richard A. Mueller ,  Francis J. Koszyk ,  Richard M. Weier

IPC分类号： C07C323/17 ,  C07C323/20 ,  C07C323/22 ,  C07C323/52 ,  C07C323/60 ,  C07D213/40 ,  C07D307/18 ,  C07D307/20 ,  C07D493/04 ,  C07D213/02 ,  A61K31/38 ,  A61K31/44 ,  C07D335/02

CPC分类号： C07D213/40 ,  C07C323/17 ,  C07C323/20 ,  C07C323/22 ,  C07C323/52 ,  C07C323/60 ,  C07D307/18 ,  C07D307/20 ,  C07D493/04 ,  C07C2101/08 ,  C07C2101/14 ,  C07C2101/18

摘要： The present invention relates to derivatives of cyclic phenolic thioethers of the formula: ##STR1## and the pharmaceutically acceptable salts thereof, which are inhibitors or stimulators of superoxide generation, and which may also inhibit cyclooxygenase and/or 5-lipoxygenase, to pharmaceutical compositions containing one or more of these compounds in combination with a pharmaceutically-acceptable carrier, and to medical methods of treatment employing these compounds.

摘要翻译： 本发明涉及以下化学式的环状酚硫醚衍生物及其药学上可接受的盐，其为抑制剂或超氧化物产生的刺激剂，并且还可以将环氧合酶和/或5-脂氧合酶抑制于含有 这些化合物中的一种或多种与药学上可接受的载体组合，以及使用这些化合物的医疗治疗方法。

公开(公告)号：US5476859A

公开(公告)日：1995-12-19

申请号：US376213

申请日：1995-01-20

申请人： Richard A. Partis ,  Francis J. Koszyk ,  Richard A. Mueller

发明人： Richard A. Partis ,  Francis J. Koszyk ,  Richard A. Mueller

IPC分类号： C07D211/46 ,  C07D401/06 ,  C07D491/04 ,  A61K31/445

CPC分类号： C07D401/06 ,  C07D211/46 ,  C07D491/04

摘要： A method of inhibiting lentivirus is disclosed which comprises mammalian host susceptible to said lentivirus with a virally inhibitory effective amount of an O-acylated derivative of 1,5-dideoxy-1,5-imino-D-glucitol and their N-alkyl, N-acyl and N-aroyl derivatives in which from one to four of the free hydroxyl groups are O-acylated with carboxylic alkanoyl radicals selected from the group consisting of .omega.,.omega.,.omega.-trifluoroalkanoyl having from three to eight carbon atoms, carboxylic cycloalkanoyl groups having from four to eight carbon atoms and carboxylic acyclic alkanoyl groups having from two to ten carbon atoms, wherein the N-aroyl groups contain from 7 to 14 carbon atoms, the N-acyl groups contain from 4 to 8 carbon atoms and the N-alkyl groups contain from 1 to 14 carbon atoms.

摘要翻译： 公开了一种抑制慢病毒的方法，其包括对所述慢病毒敏感的哺乳动物宿主，其具有病毒抑制有效量的1,5-二脱氧-1,5-亚氨基-D-葡萄糖醇的O-酰化衍生物及其N-烷基，N 酰基和N-芳酰基衍生物，其中1至4个游离羟基与选自具有3至8个碳原子的ω，ω，ω-三氟烷酰基的羧基烷酰基进行O-酰化，羧基环烷酰基 具有4至8个碳原子和具有2至10个碳原子的羧酸非环烷酰基，其中N-芳酰基含有7至14个碳原子，N-酰基含有4至8个碳原子， 烷基含有1至14个碳原子。

公开(公告)号：US5221746A

公开(公告)日：1993-06-22

申请号：US919432

申请日：1992-07-27

申请人： Richard A. Partis ,  Francis J. Koszyk ,  Richard A. Mueller

发明人： Richard A. Partis ,  Francis J. Koszyk ,  Richard A. Mueller

IPC分类号： C07D211/46 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06 ,  C07D491/04

CPC分类号： C07D401/06 ,  C07D211/46 ,  C07D405/06 ,  C07D409/06 ,  C07D491/04

摘要： O-acylated derivatives of 1,5-dideoxy-1,5-imino-D-glucitol are disclosed that contain an N-alkyl or N-aroyl radical in which from one to four of the free hydroxyl groups are O-acylated with carboxylic alkanoyl radicals selected from the group consisting of .omega.,.omega.,.omega.-trifluoro alkanoyl having from three to eight carbon atoms, carboxylic cycloalkanoyl groups having from four to eight carbon atoms and carboxylic acyclic alkanoyl groups having from two to ten carbon atoms, wherein the N-aroyl radical is selected from the group consisting of p-decylbenzoyl, 3-(p-chlorophenoxy)propanoyl, 2-(acetyloxy)benzoyl, [1,1'-biphenyl]-4-ylcarbonyl, 2-thiopheneacetyl, trans-3-furanacryloyl 3-methoxyphenylacetyl and 3-(trifluoromethyl)benzoyl, and wherein the N-alkyl contains from one to fourteen carbon atoms, provided that when N-alkyl contains from one to five carbon atoms the O-acylated groups are .omega.,.omega.,.omega.-trifluoro alkanoyl or carboxylic cycloalkanoyl.

摘要翻译： 公开了1,5-二脱氧-1,5-亚氨基-D-葡萄糖醇的O-酰化衍生物，其含有N-烷基或N-芳酰基，其中1至4个游离羟基与羧基进行O-酰化 选自具有3至8个碳原子的ω，ω，ω-三氟烷酰基，具有4至8个碳原子的羧基环烷酰基和2至10个碳原子的羧酸非环烷酰基的烷酰基，其中N 芳酰基选自对 - 癸基苯甲酰基，3-（对氯苯氧基）丙酰基，2-（乙酰氧基）苯甲酰基，[1,1'-联苯] -4-基羰基，2-噻吩乙酰基，反式-3 - 呋喃丙烯酰基3-甲氧基苯乙酰基和3-（三氟甲基）苯甲酰基，其中N-烷基含有1至14个碳原子，条件是当N-烷基含有1至5个碳原子时，O-酰化基团是ω，ω， ω-三氟烷酰基或羧酸环烷酰基。

公开(公告)号：US4937357A

公开(公告)日：1990-06-26

申请号：US410638

申请日：1989-09-26

申请人： Francis J. Koszyk ,  Richard A. Partis ,  Richard A. Mueller

发明人： Francis J. Koszyk ,  Richard A. Partis ,  Richard A. Mueller

IPC分类号： C07C43/166 ,  C07C45/40 ,  C07C47/277 ,  C07D207/12

CPC分类号： C07D207/12 ,  C07C43/166 ,  C07C45/40 ,  C07C47/277

摘要： N-alkyl, N-hydroxylalkyl and N-alkanoyl derivatives of 1,4-dideoxy-1,4-imino-L-arabinitol are disclosed in which the alkyl group has from 4 to about 9 carbon atoms, the hydroxyalkyl group has from 2 to about 5 carbon atoms and the alkanoyl group has from 3 to about 12 carbon atoms. These compounds are useful intermediates for the preparation of acylated derivatives thereof which have antiviral activity.

摘要翻译： 公开了1,4-二脱氧-1,4-亚氨基-L-阿拉伯糖醇的N-烷基，N-羟基烷基和N-烷酰基衍生物，其中烷基具有4至约9个碳原子，羟烷基具有2 至约5个碳原子，而烷酰基具有3至约12个碳原子。 这些化合物是制备其具有抗病毒活性的酰化衍生物的有用中间体。

公开(公告)号：US5310745A

公开(公告)日：1994-05-10

申请号：US929325

申请日：1992-08-13

申请人： Richard A. Partis ,  Francis J. Koszyk ,  Richard A. Mueller

发明人： Richard A. Partis ,  Francis J. Koszyk ,  Richard A. Mueller

IPC分类号： C07D211/46 ,  C07D401/06 ,  C07D491/04 ,  A61K31/445

CPC分类号： C07D401/06 ,  C07D211/46 ,  C07D491/04

摘要： A method of inhibiting lentivirus is disclosed which comprises mammalian host susceptible to said lentivirus with a virally inhibitory effective amount of an O-acylated derivative of 1,5-dideoxy-1,5-imino-D-glucitol and their N-alkyl, N-acyl and N-aroyl derivatives in which from one to four of the free hydroxyl groups are O-acylated with carboxylic alkanoyl radicals selected from the group consisting of .omega.,.omega.,.omega.-trifluoroalkanoyl having from three to eight carbon atoms, carboxylic cycloalkanoyl groups having from four to eight carbon atoms and carboxylic acyclic alkanoyl groups having from two to ten carbon atoms, wherein the N-aroyl groups contain from 7 to 14 carbon atoms, the N-acyl groups contain from 4 to 8 carbon atoms and the N-alkyl groups contain from 1 to 14 carbon atoms.

摘要翻译： 公开了一种抑制慢病毒的方法，其包括对所述慢病毒敏感的哺乳动物宿主，其具有病毒抑制有效量的1,5-二脱氧-1,5-亚氨基-D-葡萄糖醇的O-酰化衍生物及其N-烷基，N 酰基和N-芳酰基衍生物，其中1至4个游离羟基与选自具有3至8个碳原子的ω，ω，ω-三氟烷酰基的羧基烷酰基进行O-酰化，羧基环烷酰基 具有4至8个碳原子和具有2至10个碳原子的羧酸非环烷酰基，其中N-芳酰基含有7至14个碳原子，N-酰基含有4至8个碳原子， 烷基含有1至14个碳原子。

公开(公告)号：US5144037A

公开(公告)日：1992-09-01

申请号：US639613

申请日：1991-01-10

申请人： Richard A. Partis ,  Francis J. Koszyk ,  Richard A. Mueller

发明人： Richard A. Partis ,  Francis J. Koszyk ,  Richard A. Mueller

IPC分类号： A61K31/445 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61P31/12 ,  C07D211/46 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06 ,  C07D491/04 ,  C07D491/056

CPC分类号： C07D401/06 ,  C07D211/46 ,  C07D405/06 ,  C07D409/06 ,  C07D491/04

摘要： Antiviral O-acylated derivatives of 1,5-dideoxy-1,5-imino-D-glucitol are disclosed that contain an N-alkyl or N-aroyl radical in which from one to four of the free hydroxyl groups are O-acylated with carboxylic alkanoyl radicals selected from the group consisting of .omega.,.omega.,.omega.-trifluoro alkanoyl having from three to eight carbon atoms, carboxylic cycloalkanoyl groups having from four to eight carbon atoms and carboxylic acyclic alkanoyl groups having from two to ten carbon atoms, wherein the N-aroyl radical is selected from the group consisting of p-decylbenzoyl, 3-(p-chlorophenoxy)propanoyl, 2-(acetyloxy)benzoyl, [1,1'-biphenyl]-4-ylcarbonyl, 2-thiopheneacetyl, trans-3-furanacryloyl, 3-methoxyphenylacetyl and 3-(trifluoromethyl)benzoyl, and wherein the N-alkyl contains from one to fourteen carbon atoms, provided that when N-alkyl contains from one to five carbon atoms the O-acylated groups are .omega.,.omega.,.omega.-trifluoro alkanoyl or carboxylic cycloalkanoyl.

摘要翻译： 公开了1,5-二脱氧-1,5-亚氨基-D-葡萄糖醇的抗病毒O-酰化衍生物，其含有N-烷基或N-芳酰基，其中一至四个游离羟基与O- 选自具有3至8个碳原子的ω，ω，ω-三氟烷酰基，具有4至8个碳原子的羧基环烷酰基和2至10个碳原子的羧酸非环烷酰基的羧基烷酰基，其中 N-芳酰基选自对 - 癸基苯甲酰基，3-（对氯苯氧基）丙酰基，2-（乙酰氧基）苯甲酰基，[1,1'-联苯] -4-基羰基，2-噻吩乙酰基， 3-呋喃丙酰基，3-甲氧基苯乙酰基和3-（三氟甲基）苯甲酰基，其中N-烷基含有1至14个碳原子，条件是当N-烷基含有1至5个碳原子时，O-酰化基团为ω， ω，ω-三氟烷酰基或羧基环烷酰基。