公开(公告)号：US4362732A

公开(公告)日：1982-12-07

申请号：US349749

申请日：1982-02-18

申请人： Walter Hunkeler ,  Emilio Kyburz

发明人： Walter Hunkeler ,  Emilio Kyburz

IPC分类号： A61K31/55 ,  A61P33/10 ,  A61P39/02 ,  A61P43/00 ,  C07D471/04 ,  C07D471/14 ,  C07D487/04 ,  C07D495/04 ,  C07D495/14

CPC分类号： C07D471/04 ,  A61K31/55 ,  C07D471/14 ,  C07D487/04 ,  C07D495/04 ,  C07D495/14

摘要： There is presented imidazodiazepines of the formula ##STR1## wherein A together with the two carbon atoms denoted as .alpha. and .beta. is a pyridine ring, X is an oxygen or sulphur atom, R.sup.1 is hydrogen, halogen, lower alkyl, lower alkoxymethyl or the group--COOR.sup.3 and R.sup.2 and R.sup.3 each are lower alkyl, and their pharmaceutically acceptable acid addition salts. The compounds are useful in the antagonization of the central-depressant, muscle relaxant, ataxic, blood pressure-lowering and respiratory-depressant properties of 1,4-benzodiazepines which have tranquillizing activity, for example as antidotes in the case of intoxications with 1,4-benzodiazepines which have tranquillizing activity.Also presented are methods to produce such imidazodiazepines.

摘要翻译： 提出了下式的咪唑并二氮杂其中A与表示为α和β的两个碳原子一起为吡啶环，X为氧或硫原子，R 1为氢，卤素，低级烷基，低级烷氧基甲基或 基团-COOR 3和R 2和R 3各自为低级烷基，及其药学上可接受的酸加成盐。 该化合物可用于拮抗具有镇静作用的1,4-苯二氮卓类的中枢抑制剂，肌肉松弛剂，共济失调，降血压和呼吸抑制剂性质，例如作为解毒剂，在1例中毒的情况下， 具有镇静作用的4-苯并二氮杂。 还提出了产生这种咪唑并氮卓类的方法。

公开(公告)号：US4346035A

公开(公告)日：1982-08-24

申请号：US322031

申请日：1981-11-16

申请人： Max Gerecke ,  Willy Haefely ,  Walter Hunkeler ,  Emilio Kyburz ,  Hanns Mohler ,  Lorenzo Pieri ,  Petar Polc

发明人： Max Gerecke ,  Willy Haefely ,  Walter Hunkeler ,  Emilio Kyburz ,  Hanns Mohler ,  Lorenzo Pieri ,  Petar Polc

IPC分类号： A61K31/55 ,  A61K31/551 ,  A61P33/10 ,  A61P39/02 ,  C07D243/14 ,  C07D243/16 ,  C07D243/18 ,  C07D243/24 ,  C07D265/26 ,  C07D333/42 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  C07D495/22 ,  C07D498/04 ,  C07D513/14

CPC分类号： C07D265/26 ,  C07D243/14 ,  C07D333/42 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  Y10S514/823 ,  Y10S514/906 ,  Y10S514/929 ,  Y10S514/96 ,  Y10S514/962 ,  Y10S514/966

摘要： Imidazodiazepine derivatives of the formula ##STR1## wherein A together with the two carbon atoms denoted as .alpha. and .beta. is selected from the group consisting of ##STR2## the dotted line represents the double bond present in groups (a) and (b), D is >C.dbd.O or >C.dbd.S, R.sup.1 is selected from the group consisting of cyano, lower alkanoyl and a group of the formula --COOR.sup.4, R.sup.4 is selected from the group consisting of methyl, ethyl, isopropyl and 2-hydroxyethyl, R.sup.5 is selected from the group consisting of hydrogen, trifluoromethyl and halogen and R.sup.6 is selected from the group consisting of hydrogen, trifluoromethyl, halogen and lower alkyl and either R.sup.2 is hydrogen and R.sup.3 is hydrogen or lower alkyl or R.sup.2 and R.sup.3 together are trimethylene or propenylene and the carbon atom denoted as .gamma. has the S- or R,S-configuration,and pharmaceutically acceptable salts thereof are presented and have utility for antagonizing the central-depressant, muscle relaxant, ataxic, blood pressure-lowering and respiratory-depressant properties of 1,4-benzodiazepines which have tranquilizing activity. They can be used, for example, as antidotes in the case of intoxications in which excessive intake of 1,4-benzodiazepines which have tranquilizing participates, or for shortening an anaesthesia induced by such 1,4-benzodiazepines. They can also be used for suppressing the activities on the central nervous system of 1,4-benzodiazepines used in other fields of indication, for example of schistosomicidally-active 1,4-benzodiazepines such as (+)-5-(o-chlorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazepin-2-one.Also presented are processes to produce the imidazodiazepine derivatives and intermediates therefor.

摘要翻译： 其中A与表示为α和β的两个碳原子一起选自由下列组成的组的虚线表示式（a）和（b）中存在的双键： D是> C = O或> C = S，R 1选自氰基，低级烷酰基和式-COOR 4基团，R 4选自甲基，乙基，异丙基和2-羟基乙基 R5选自氢，三氟甲基和卤素，R6选自氢，三氟甲基，卤素和低级烷基，R2是氢，R3是氢或低级烷基或R2和R3一起是三亚甲基 或丙烯并且表示为γ的碳原子具有S-或R，S-构型及其药学上可接受的盐，并且具有拮抗中枢抑制剂，肌肉松弛剂，共济失调，降血压和呼吸的效用 具有镇静活性的1,4-苯并二氮杂的抑制剂性质。 例如，可以使用它们作为解毒剂，在中毒的情况下，过量摄入具有镇静作用的1,4-苯二氮卓类药物，或用于缩短由该1,4-苯并二氮杂卓引起的麻醉。 它们还可用于抑制其他适应症领域中使用的1,4-苯并二氮杂类的中枢神经系统的活性，例如血吸虫半衰期活性1,4-苯并二氮杂如（+） - 5-（邻 - 氯苯基） ）-1,3-二氢-3-甲基-7-硝基-2H-1,4-苯并二氮杂-2-酮。 还提出了产生咪唑并氮杂衍生物的方法及其中间体。

公开(公告)号：US4316839A

公开(公告)日：1982-02-23

申请号：US193775

申请日：1980-10-03

申请人： Max Gerecke ,  Willy Haefely ,  Walter Hunkeler ,  Emilio Kyburz ,  Hanns Mohler ,  Lorenzo Pieri ,  Petar Polc

发明人： Max Gerecke ,  Willy Haefely ,  Walter Hunkeler ,  Emilio Kyburz ,  Hanns Mohler ,  Lorenzo Pieri ,  Petar Polc

IPC分类号： A61K31/55 ,  A61K31/551 ,  A61P33/10 ,  A61P39/02 ,  C07D243/14 ,  C07D243/16 ,  C07D243/18 ,  C07D243/24 ,  C07D265/26 ,  C07D333/42 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  C07D495/22 ,  C07D498/04 ,  C07D513/14

CPC分类号： C07D265/26 ,  C07D243/14 ,  C07D333/42 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  Y10S514/823 ,  Y10S514/906 ,  Y10S514/929 ,  Y10S514/96 ,  Y10S514/962 ,  Y10S514/966

摘要： Imidazodiazepine derivatives of the formula ##STR1## wherein A together with the two carbon atoms denoted as .alpha. and .beta. is selected from the group consisting of ##STR2## the dotted line represents the double bond present in groups (a) and (b), D is >C.dbd.O or >C.dbd.S, R.sup.1 is selected from the group consisting of cyano, lower alkanoyl and a group of the formula --COOR.sup.4, R.sup.4 is selected from the group consisting of methyl, ethyl, isopropyl and 2-hydroxyethyl, R.sup.5 is selected from the group consisting of hydrogen, trifluoromethyl and halogen and R.sup.6 is selected from the group consisting of hydrogen, trifluoromethyl, halogen and lower alkyl and either R.sup.2 is hydrogen and R.sup.3 is hydrogen or lower alkyl or R.sup.2 and R.sup.3 together are trimethylene or propenylene and the carbon atom denoted as .gamma. has the S- or R,S-configuration, and pharmaceutically acceptable salts thereof are presented and have utility for antagonizing the central-depressant, muscle relaxant, ataxic, blood pressure-lowering and respiratory-depressant properties of 1,4-benzodiazepines which have tranquillizing activity. They can be used, for example, as antidotes in the case of intoxications in which excessive intake of 1,4-benzodiazepines which have tranquillizing participates, or for shortening an anaesthesia induced by such 1,4-benzodiazepines. They can also be used for suppressing the activities on the central nervous system of 1,4-benzodiazepines used in other fields of indication, for example of schistosomicidally-active 1,4-benzodiazepines such as (+)-5-(o-chlorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazepin-2-one.Also presented are processes to produce the imidazodiazepine derivatives and intermediates therefor.

摘要翻译： 其中A与表示为α和β的两个碳原子一起选自由下列组成的组的虚线表示式（a）和（b）中存在的双键： D是> C = O或> C = S，R 1选自氰基，低级烷酰基和式-COOR 4基团，R 4选自甲基，乙基，异丙基和2-羟基乙基 R5选自氢，三氟甲基和卤素，R6选自氢，三氟甲基，卤素和低级烷基，R2是氢，R3是氢或低级烷基或R2和R3一起是三亚甲基 或丙烯并且表示为γ的碳原子具有S-或R，S-构型及其药学上可接受的盐，并且具有拮抗中枢抑制剂，肌肉松弛剂，共济失调，降血压和呼吸的效用 具有镇静作用的1,4-苯并二氮杂类的抑制剂性质。 例如，可以使用它们作为解毒剂，在中毒的情况下，过量摄入具有镇静作用的1,4-苯二氮卓类药物参与，或用于缩短由1,4-苯并二氮杂卓诱导的麻醉。 它们还可用于抑制其他适应症领域中使用的1,4-苯并二氮杂类的中枢神经系统的活性，例如血吸虫半衰期活性1,4-苯并二氮杂如（+） - 5-（邻 - 氯苯基） ）-1,3-二氢-3-甲基-7-硝基-2H-1,4-苯并二氮杂-2-酮。 还提出了产生咪唑并氮杂衍生物的方法及其中间体。

公开(公告)号：US4239770A

公开(公告)日：1980-12-16

申请号：US8674

申请日：1979-02-02

申请人： Emilio Kyburz ,  Werner Aschwanden

发明人： Emilio Kyburz ,  Werner Aschwanden

IPC分类号： C07D207/267 ,  A61K31/40 ,  A61K31/4015 ,  A61K38/35 ,  A61P25/28 ,  C07D207/26 ,  C07D207/263 ,  C07D207/27

CPC分类号： C07D207/27 ,  Y10S514/811 ,  Y10S514/879

摘要： 1-Substituted 2-pyrrolidinones and pharmaceutical compositions containing same are described. The pharmaceutical compositions are useful in counteracting cerebral insufficiency or improving intellectual capacity.

摘要翻译： 描述1-取代的2-吡咯烷酮和含有它们的药物组合物。 药物组合物可用于抵抗脑功能不全或提高智力能力。

公开(公告)号：US4003915A

公开(公告)日：1977-01-18

申请号：US588268

申请日：1975-06-19

申请人： Philippe Dostert ,  Emilio Kyburz

发明人： Philippe Dostert ,  Emilio Kyburz

IPC分类号： C07C65/36 ,  C07D337/12

CPC分类号： C07C65/36

摘要： Tricyclic imines of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, m and n are as hereinafter described, prepared from the corresponding ketones of the formula ##STR2## wherein R.sup.1, X and m are as hereinafter described, are disclosed. The compounds of formula I are useful as antidepressants, as well as anticonvulsants and agents for the treatment of Parkinsonism.

摘要翻译： 其中R 1，R 2，R 3，R 4，X，m和n如下文所述，由下式其中R 1，X和m如下文所述的相应的酮制备的式（I）所示的三环亚胺 ，被披露。 式I的化合物可用作抗抑郁药，以及抗惊厥药和用于治疗帕金森综合征的药剂。

公开(公告)号：US3952017A

公开(公告)日：1976-04-20

申请号：US501931

申请日：1974-08-30

申请人： Emilio Kyburz ,  Hans Spiegelberg

发明人： Emilio Kyburz ,  Hans Spiegelberg

IPC分类号： C07C13/547 ,  C07C63/331 ,  C07C65/38 ,  C07C93/00 ,  C07D317/28

CPC分类号： C07C63/331 ,  C07C13/547 ,  C07C65/38 ,  C07C2103/32 ,  Y10S514/96

摘要： 1-Methyl(or acetyl)-5H-dibenzo[a,d]cycloheptenes and 1-methyl(or acetyl)-10,11-dihydro-5H-dibenzo[a,d]cycloheptenes bearing a basic side chain at the 5-position, such as a 3-mono- or dimethylaminopropylidene, a 3-mono- or dimethylaminopropyl or a 3-dimethylaminopropylidene(or propyl)-N-oxide, intermediates and processes for their preparation, are described. The end products are useful antidepressants.

摘要翻译： 1-甲基（或乙酰基）-5H-二苯并[a，d]环庚烯和1-甲基（或乙酰基）-10,11-二氢-5H-二苯并[a，d]环庚烯， 描述了3-单或二甲基亚氨基，3-单或二甲基氨基丙基或3-二甲基氨基亚丙基（或丙基）-N-氧化物的中间体及其制备方法。 最终产品是有用的抗抑郁药。

公开(公告)号：US4957911A

公开(公告)日：1990-09-18

申请号：US395380

申请日：1989-08-17

申请人： Werner Aschwanden ,  Rene Imhof ,  Roland Jakob ,  Emilio Kyburz

发明人： Werner Aschwanden ,  Rene Imhof ,  Roland Jakob ,  Emilio Kyburz

IPC分类号： A61K31/395 ,  A61P25/28 ,  C07D221/10 ,  C07D225/06

CPC分类号： C07D221/10 ,  C07D225/06

摘要： Benzazecinediones of the formula ##STR1## wherein R.sup.1 and R.sup.2 are independently hydrogen or chlorine, R.sup.3 is hydrogen, fluorine, chlorine, bromine or methoxy, R.sup.4 is hydrogen, chlorine or methoxy and R.sup.5 is hydrogen, acetyl, propionyl, benzoyl, chlorobenzoyl, methoxybenzoyl or phenylacetyl, with the proviso that 2 or 3 of the groups R.sup.1 to R.sup.4 are hydrogen, as well as many of the corresponding benzo[f]quinolines from which these benzazecinediones can be prepared by oxidation are suitable for the control or prevention of cerebral insufficiency or for the improvement of cognitive functions in mammals. They can be produced according to various processes and can be prepared into pharmaceutical compositions.

公开(公告)号：US4883815A

公开(公告)日：1989-11-28

申请号：US215003

申请日：1988-07-05

申请人： Werner Aschwenden ,  Rene Imhof ,  Roland Jakob-Roetne ,  Emilio Kyburz

发明人： Werner Aschwenden ,  Rene Imhof ,  Roland Jakob-Roetne ,  Emilio Kyburz

IPC分类号： C07D221/10 ,  A61K31/165 ,  A61K31/325 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/445 ,  A61K31/47 ,  A61K31/473 ,  A61P25/28 ,  C07C67/00 ,  C07C231/00 ,  C07C231/02 ,  C07C231/12 ,  C07C233/47 ,  C07C235/52 ,  C07C237/12 ,  C07C237/20 ,  C07C237/22 ,  C07C237/36 ,  C07C239/00 ,  C07C275/24 ,  C07D213/30 ,  C07D213/75 ,  C07D213/81 ,  C07D225/06 ,  C07D295/13 ,  C07D295/185

CPC分类号： C07D213/75 ,  C07D213/81 ,  C07D295/13 ,  C07D295/185

摘要： Hydrocinnamic acid derivatives of the formula ##STR1## wherein one or two of the symbols R.sup.1 to R.sup.4 are halogen or methoxy and the others are hydrogen;R.sup.5 is hydrogen or phenyl;R.sup.6 is a residue of the formula ##STR2## R.sup.7 is (C.sub.1 -C.sub.4)-alkyl, (C.sub.2 -C.sub.5)-alkanoylamino-(C.sub.2 -C.sub.5)-alkyl, amino or (C.sub.1 -C.sub.4)-alkoxyphenyl;R.sup.8 and R.sup.9 each, independently, are hydrogen or (C.sub.1 -C.sub.4)-alkyl;R.sup.10 is hydrogen and R.sup.11 is hydroxy or R.sup.10 and R.sup.11 taken together are oxo;R.sup.12 is hydrogen, (C.sub.1 -C.sub.10)-alkyl, pyridylmethyl or carbamoylmethyl;R.sup.13 is hydrogen, (C.sub.1 -C.sub.4)-alkyl and R.sup.14 is hydrogen, (C.sub.1 -C.sub.4)-alkyl, pyridyl, phenyl-(C.sub.1 -C.sub.4)-alkyl, carboxy-(C.sub.1 -C.sub.4)-alkyl, carbamoyl-(C.sub.1 -C.sub.4)-alkyl, (C.sub.1 -C.sub.4)-alkoxy carbonyl-(C.sub.1 -C.sub.4)-alkyl, di-(C.sub.1 -C.sub.4)-alkoxy carbonyl-C.sub.2 -C.sub.5)-alky, piperidino-C.sub.2 -C.sub.4)-alkyl or halopyridinecarboxamido-(C.sub.2 -C.sub.4)-alkyl or R.sup.13 and R.sup.14 taken together with the nitrogen atom are 4-(C.sub.1 -C.sub.4)-alkyl-piperazin-1-yl,as well as pharmaceutically acceptable salts of basic compounds of formula I with acids or of acidic compounds of formula I with bases are described. The compounds of formula I and their pharmaceutically acceptable salts are suitable for the control or prevention of cerebral insufficiency or for the improvement of cognitive functions.

摘要翻译： 其中一个或两个符号R 1至R 4为卤素或甲氧基，而其余为氢的式I的氢化肉桂酸衍生物; R5是氢或苯基; R 6是下式的残基：R 7是（C 1 -C 4） - 烷基，（C 2 -C 5） - 烷酰基氨基 - （C 2 -C 5） - 烷基，氨基或（C 1 -C 4） - 烷氧基苯基; R 8和R 9各自独立地为氢或（C 1 -C 4） - 烷基; R 10是氢，R 11是羟基或R 10和R 11一起是氧代; R 12是氢，（C 1 -C 10） - 烷基，吡啶基甲基或氨基甲酰基甲基; R 1是氢，（C 1 -C 4） - 烷基，R 14是氢，（C 1 -C 4） - 烷基，吡啶基，苯基 - （C 1 -C 4） - 烷基，羧基 - （C 1 -C 4） - 烷基，氨基甲酰基 - -C 1-4） - 烷基，（C 1 -C 4） - 烷氧基羰基 - （C 1 -C 4） - 烷基，二 - （C 1 -C 4） - 烷氧基羰基-C 2 -C 5） - 烷基，哌啶子基-C 2 -C 4） - 烷基或 卤代吡啶甲酰氨基 - （C 2 -C 4） - 烷基或R 13和R 14与氮原子一起是4-（C 1 -C 4） - 烷基 - 哌嗪-1-基，以及式I的碱性化合物与酸的药学上可接受的盐 或具有碱的酸式酸式化合物。 式I化合物及其药学上可接受的盐适用于控制或预防脑功能不全或改善认知功能。

公开(公告)号：US4775671A

公开(公告)日：1988-10-04

申请号：US122106

申请日：1987-11-18

申请人： Walter Hunkeler ,  Emilio Kyburz

发明人： Walter Hunkeler ,  Emilio Kyburz

IPC分类号： A61K31/55 ,  A61P21/02 ,  A61P25/08 ,  A61P25/20 ,  C07D243/00 ,  C07D243/14 ,  C07D333/00 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  C07D495/22

CPC分类号： C07D487/04 ,  C07D243/14 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14

摘要： There is presented compounds of the formula ##STR1## wherein A together with the two carbon atoms denoted by .alpha. and .beta. signifies one of the groups ##STR2## and the dotted line signifies the double bond present in cases (1), (2) and (4) and wherein R.sup.1 signifies a 5- or 6-membered aromatic heterocyclic group or the group --C(R.sup.6).dbd.NOR.sup.7 (B), R.sup.2 signifies hydrogen and R.sup.3 signifies hydrogen or lower alkyl or R.sup.2 and R.sup.3 together signify dimethylene, trimethylene or propenylene, R.sup.4 and R.sup.5 each signify hydrogen, halogen, trifluoromethyl, cyano, nitro, amino or lower alkyl, R.sup.6 signifies hydrogen or lower alkyl and R.sup.7 signifies lower alkyl, the compound of formula I having the (S) or (R,S) configuration with reference to the carbon atom denoted by .gamma. when R.sup.2 and R.sup.3 together signify dimethylene, trimethylene or propenylene, and pharmaceutically acceptable acid addition salts thereof have a pronounced affinity to the central benzodiazepine receptors and have anxiolytic, anticonvulsant, muscle relaxant and sedative-hypnotic properties.

摘要翻译： 呈现下式的化合物，其中A与由α和β表示的两个碳原子一起表示组之一，其中一个组（1）（2）（3）和

公开(公告)号：US4764522A

公开(公告)日：1988-08-16

申请号：US766364

申请日：1985-08-16

申请人： Rene Imhof ,  Emilio Kyburz

发明人： Rene Imhof ,  Emilio Kyburz

IPC分类号： C07D263/18 ,  A61K9/20 ,  A61K9/48 ,  A61K31/34 ,  A61K31/341 ,  A61K31/345 ,  A61K31/38 ,  A61K31/381 ,  A61K31/425 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4412 ,  A61K31/4418 ,  A61K31/455 ,  A61K31/495 ,  A61K31/496 ,  A61P25/00 ,  A61P25/24 ,  A61P25/26 ,  A61P43/00 ,  C07D213/79 ,  C07D213/80 ,  C07D213/81 ,  C07D213/84 ,  C07D241/06 ,  C07D241/24 ,  C07D261/18 ,  C07D263/34 ,  C07D277/20 ,  C07D277/46 ,  C07D277/56 ,  C07D307/68 ,  C07D333/38

CPC分类号： C07D213/81 ,  A61K9/2018 ,  A61K9/4858 ,  C07D213/84 ,  C07D241/06 ,  C07D261/18 ,  C07D263/34 ,  C07D277/56 ,  C07D307/68 ,  C07D333/38

摘要： Compounds of the formula ##STR1## wherein R is an aromatic, 5- or 6-membered heterocyclic residue, as described herein, and their pharmaceutically usable acid addition salts are described. These compounds have interesting monoamine oxidase inhibiting properties with low toxicity and can accordingly be used for the treatment of depressive states and parkinsonism.

摘要翻译： 描述了其中R是如本文所述的芳族，5或6元杂环残基及其药学上可用的酸加成盐的式（I）的化合物。 这些化合物具有低毒性的有意义的单胺氧化酶抑制性质，因此可用于治疗抑郁状态和帕金森综合征。