公开(公告)号：US4959361A

公开(公告)日：1990-09-25

申请号：US252964

申请日：1988-10-03

申请人： Armin Walser

发明人： Armin Walser

IPC分类号： C07D487/04 ,  C07D495/14 ,  C07D519/00 ,  C07F7/08

CPC分类号： C07D487/04 ,  C07D495/14 ,  C07F7/0812

摘要： The invention relates to compounds of the formula ##STR1## wherein X is --CH.dbd.CH-- or S; R.sub.1 is lower alkyl, lower alkoxy or trifluoromethyl;R.sub.2 is hydrogen, lower alkyl, lower alkoxy, hydroxy or alkanoyloxy;R.sub.3 and R.sub.4, independently, are hydrogen, chlorine, fluorine, lower alkyl or lower alkoxy;s is an integer from 0 to 1, provided that when s is 1,R.sub.2 cannot be hydroxy, lower alkoxy or alkanoyloxy;R.sub.5 is a radical of the formula R.sub.6 --(CH.sub.2).sub.n -- or R.sub.7 --O--(CH.sub.2).sub.m --wherein R.sub.6 and R.sub.7 are aryl or a heterocyclic radical, n is an integer of from 0 to 2 and m is an integer of from 1 to 2, provided that, when n is 0, R.sub.6 must be attached through a carbon to carbon bond, and provided that R.sub.7 is always attached through a carbon to oxygen bond,and, when at least one asymmetric carbon is present, its enantiomers and racemates, and pharmaceutically acceptable acid addition salts thereof.The compounds of formula I exhibit activity as platelet activating factor (PAF) antagonists and are, therefore, useful in disease states characterized by excess platelet activating factor or for the prevention and treatment of cardiovascular diseases, pulmonary diseases, immunological disorders, inflammatory diseases, dermatological disorders, shock or transplant rejection.

摘要翻译： 本发明涉及下式化合物其中X为-CH = CH-或S; R1是低级烷基，低级烷氧基或三氟甲基; R2是氢，低级烷基，低级烷氧基，羟基或烷酰氧基; R 3和R 4独立地是氢，氯，氟，低级烷基或低级烷氧基; s为0〜1的整数，条件是当s为1时，R2不能为羟基，低级烷氧基或烷酰氧基; R5是式R6-（CH2）n-或R7-O-（CH2）m-的基团，其中R6和R7是芳基或杂环基，n是0-2的整数，m是 1至2，条件是当n为0时，R 6必须通过碳 - 碳键连接，并且条件是R7总是通过碳与氧键连接，并且当存在至少一个不对称碳时，其 对映异构体和外消旋物，及其药学上可接受的酸加成盐。 式I化合物表现出作为血小板活化因子（PAF）拮抗剂的活性，因此可用于以过量血小板活化因子为特征的疾病状态或用于预防和治疗心血管疾病，肺部疾病，免疫学疾病，炎性疾病，皮肤病学 疾病，休克或移植排斥。

公开(公告)号：US4481142A

公开(公告)日：1984-11-06

申请号：US437047

申请日：1982-10-27

申请人： Rodney I. Fryer ,  Norman W. Gilman ,  Eugene J. Trybulski ,  Armin Walser

发明人： Rodney I. Fryer ,  Norman W. Gilman ,  Eugene J. Trybulski ,  Armin Walser

IPC分类号： C07C45/63 ,  C07C45/68 ,  C07C45/71 ,  C07C65/34 ,  C07C291/04 ,  C07C309/66 ,  C07D209/48 ,  C07D223/16 ,  C07D239/42 ,  C07D317/16 ,  C07D317/30 ,  C07D487/04

CPC分类号： C07D209/48 ,  C07C291/04 ,  C07C309/66 ,  C07C45/63 ,  C07C45/68 ,  C07C45/71 ,  C07C65/34 ,  C07D223/16 ,  C07D239/42 ,  C07D317/16 ,  C07D317/30 ,  C07D487/04

摘要： There is presented compounds of the formula ##STR1## wherein A is selected from the group consisting of ##STR2## R.sub.1 is selected from the group consisting of hydrogen, chlorine, bromine, lower alkyl, the group NR.sub.4 R.sub.5, the group --CH.sub.2 --CO--R.sub.7, the group--NH(CH.sub.2).sub.m NR.sub.8 R.sub.9, hydroxy, lower alkoxy, mercapto and lower alkyl mercapto; R.sub.2 is selected from the group consisting of hydrogen, amino and dilower alkyl amino; R.sub.3 is selected from the group consisting of hydrogen, lower acyloxy and hydroxy; X is selected from the group consisting of hydrogen, halogen, trifluoromethyl, ethyl, .alpha.-hydroxy ethyl and acetyl; Y is hydrogen or halogen; R.sub.4 and R.sub.5 are hydrogen or lower alkyl or together with their co-bonded nitrogen atom form a five to seven membered heterocyclic group; R.sub.7 is selected from the group consisting of hydroxy lower alkoxy and NR.sub.8 R.sub.9 ; R.sub.8 and R.sub.9 are hydrogen or lower alkyl; n is 0 or 1 and m is 1 to 7 with the limitations that (1) at least one of R.sub.1 and R.sub.2 are hydrogen, (2) when R.sub.3 is lower acyloxy or hydroxy, A is the group (a), X is hydrogen, halogen, trifluoromethyl, ethyl or acetyl and R.sub.1 is the group --NH(CH.sub.2).sub.m NR.sub.8 R.sub.9, then R.sub.8 and R.sub.9 are lower alkyl, (3) when A is group (d) and R.sub.1 is the group --NH(CH.sub.2).sub.m NR.sub.8 R.sub.9 then R.sub.8 and R.sub.9 are lower alkyl and (4) when n is 1, R.sub.1 is hydrogen, lower alkyl, lower alkoxy, chlorine, bromine or the group --CH.sub.2 --CO-- R.sub.7 with R.sub.7 as above then A is the group (a) or (b) and the pharmaceutically acceptable salts thereof.The compounds exhibit pharmacological activity as anxiolytics and sedatives.Also presented Are various novel intermediates and processes to produce the above end products.

摘要翻译： 提供式IMA的化合物，其中A选自由下列组成的组：R 1选自氢，氯，溴，低级烷基，NR 4 R 5基团，基团 -CH 2 -CO-R 7，基团-NH（CH 2）m NR 8 R 9，羟基，低级烷氧基，巯基和低级烷基巯基; R2选自氢，氨基和二元烷基氨基; R3选自氢，低级酰氧基和羟基; X选自氢，卤素，三氟甲基，乙基，α-羟基乙基和乙酰基; Y是氢或卤素; R4和R5是氢或低级烷基，或与它们的共键键合的氮原子一起形成5至7元杂环基; R7选自羟基低级烷氧基和NR8R9; R8和R9是氢或低级烷基; n为0或1，m为1至7，限制为（1）R 1和R 2中的至少一个为氢，（2）当R3为酰氧基或羟基时，A为（a），X为氢 ，卤素，三氟甲基，乙基或乙酰基，R 1为基团-NH（CH 2）m NR 8 R 9，则R 8和R 9为低级烷基，（3）当A为基团（d）且R 1为基团-NH（CH 2）m NR 8 R 9时 R8和R9为低级烷基，（4）当n为1时，R1为氢，低级烷基，低级烷氧基，氯，溴或基团-CH2-CO- R7，R7为上述，则A为（a）或 （b）及其药学上可接受的盐。 该化合物显示出作为抗焦虑药和镇静剂的药理活性。 还提出了各种新型中间体和方法来生产上述最终产品。

公开(公告)号：US4436662A

公开(公告)日：1984-03-13

申请号：US481021

申请日：1983-03-31

申请人： Rodney I. Fryer ,  Eugene J. Trybulski ,  Armin Walser

发明人： Rodney I. Fryer ,  Eugene J. Trybulski ,  Armin Walser

IPC分类号： C07C29/147 ,  C07C45/30 ,  C07C51/347 ,  C07D207/34 ,  C07D209/94 ,  C07D487/04 ,  C07D487/02

CPC分类号： C07D487/04 ,  C07C255/00 ,  C07C29/147 ,  C07C45/305 ,  C07C51/347 ,  C07D207/34 ,  C07D209/94

摘要： The present invention relates to compounds of the formula ##STR1## wherein R.sub.1 and R.sub.3 are selected from the group consisting of hydrogen, lower alkyl, hydroxy, lower alkoxy or acyloxy and R.sub.2 and R.sub.4 are hydrogen or R.sub.1 and R.sub.2 and/or R.sub.3 and R.sub.4 taken together are oxo groups with the proviso that at least one oxo group is present; R is selected from the group consisting of hydrogen, lower alkyl, C.sub.2 to C.sub.7 carboxylic acids and the esters and amides thereof, hydroxy C.sub.2 to C.sub.7 alkyl and amino C.sub.2 to C.sub.7 alkyl or mono- or di-lower alkyl amino C.sub.2 to C.sub.7 alkyl; R.sub.5 is halogen or hydrogen; and R.sub.6 is halogen with the proviso that when R.sub.1 or R.sub.3 is hydroxy, lower alkoxy or acyloxy, then R is lower alkyl or hydrogen and the N-oxides and the pharmaceutically acceptable salts thereof.

摘要翻译： 本发明涉及下式化合物：其中R1和R3选自氢，低级烷基，羟基，低级烷氧基或酰氧基，R2和R4是氢或R1，R2和/或R3和R4 一起是氧基，条件是存在至少一个氧代基团; R选自氢，低级烷基，C 2至C 7羧酸及其酯和酰胺，羟基C 2至C 7烷基和氨基C 2至C 7烷基或单 - 或二 - 低级烷基氨基C 2至C 7烷基; R5是卤素或氢; 并且R 6为卤素，条件是当R 1或R 3为羟基，低级烷氧基或酰氧基时，则R为低级烷基或氢，以及其N-氧化物及其药学上可接受的盐。

公开(公告)号：US4371468A

公开(公告)日：1983-02-01

申请号：US244511

申请日：1981-03-16

申请人： Armin Walser ,  Rodney I. Fryer

发明人： Armin Walser ,  Rodney I. Fryer

IPC分类号： C07D243/16 ,  C07D243/20 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  C07F9/6561 ,  C07D401/04

CPC分类号： C07D487/04 ,  C07D243/16 ,  C07D243/20 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  C07F9/6561

摘要： Novel imidazobenzodiazepines and their analogs are useful as anticonvulsants, muscle relaxant, anxiolytic and sedative agents. Preferred compounds of this class belong to the imidazo[1,5-a][1,4]diazepine series which may have a very wide variety of organic substituents. As especially preferred genus included within the purview of the invention encompasses a compound of the formula ##STR1## wherein R.sub.1 is hydrogen and lower alkyl, preferably methyl; R.sub.3 and R.sub.5 are hydrogen; R.sub.4 is hydrogen, nitro and halogen, most preferably chlorine, and in a most preferred embodiment when positioned on the fused benzo portion of the imidazobenzodiazepine is in the 8-position thereof. R.sub.6 is phenyl or halo, nitro, or lower alkyl-substituted phenyl, preferably halo, with fluorine being the preferred halogen, the substituted fluoro being positioned in the 2-position of the phenyl moiety and R.sub.2 is hydrogen and lower alkyl.

公开(公告)号：US4280957A

公开(公告)日：1981-07-28

申请号：US905820

申请日：1978-05-15

申请人： Armin Walser ,  Rodney I. Fryer

发明人： Armin Walser ,  Rodney I. Fryer

IPC分类号： C07D243/16 ,  C07D243/20 ,  C07D285/10 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  C07F9/6561

CPC分类号： C07D285/10 ,  C07D243/16 ,  C07D243/20 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D495/14 ,  C07F9/6561 ,  Y10S514/906 ,  Y10S514/96

摘要： Novel Imidazobenzodiazepines and their analogs are useful as anticonvulsants, muscle relaxant, anxiolytic and sedative agents. Preferred compounds of this class belong to the imidazo[1,5-a][1,4]diazepine series which may have a very wide variety of organic substituents. An especially preferred genus included within the purview of the invention encompasses a compound of the formula ##STR1## wherein R.sub.1 is hydrogen and lower alkyl preferably methyl; R.sub.3 and R.sub.5 are hydrogen; R.sub.4 is hydrogen, nitro and halogen, most preferably, chlorine, and in a most preferred embodiment when positioned on the fused benzo portion of the imidazobenzodiazepine is in the 8-position thereof, R.sub.6 is phenyl or halo, nitro, or lower alkyl-substituted phenyl, preferably, halo, with fluorine being the preferred halogen, the substituted fluoro being positioned in the 2-position of the phenyl moiety and R.sub.2 is hydrogen and lower alkyl.

摘要翻译： 新型咪唑并二氮杂类及其类似物可用作抗惊厥药，肌肉松弛剂，抗焦虑药和镇静剂。 该类的优选化合物属于可能具有非常多种有机取代基的咪唑并[1,5-a] [1,4]二氮杂类。 包括在本发明的范围内的特别优选的类包括式IMA的化合物，其中R 1是氢，低级烷基优选是甲基; R3和R5是氢; R4是氢，硝基和卤素，最优选氯，最优选的实施方案中，当位于咪唑并二氮杂的稠合苯并部分位于其8-位时，R 6是苯基或卤素，硝基或低级烷基取代的 苯基，优选卤素，氟是优选的卤素，取代的氟位于苯基部分的2-位，并且R 2是氢和低级烷基。

公开(公告)号：US4125726A

公开(公告)日：1978-11-14

申请号：US776820

申请日：1977-03-11

申请人： Armin Walser ,  Rodney I. Fryer ,  Louis Benjamin

发明人： Armin Walser ,  Rodney I. Fryer ,  Louis Benjamin

IPC分类号： A61K31/55 ,  A61P21/02 ,  A61P25/20 ,  A61P25/26 ,  C07D243/16 ,  C07D487/04

CPC分类号： C07D487/04 ,  C07D243/16

摘要： Compounds are disclosed of the formula ##STR1## wherein R.sub.1 is hydrogen, halogen or trifluoromethyl; R.sub.2 is selected from the group consisting of lower alkylthio together with the sulfoxide and sulfone thereof, halo, lower alkylamino or lower alkoxy; Y is oxo or thio; R.sub.3 is selected from the group consisting of hydrogen, --COOR.sub.4 wherein R.sub.4 is hydrogen or lower alkyl, --CONR.sub.6 R.sub.5 wherein R.sub.5 and R.sub.6 are hydrogen or lower alkyl; X is hydrogen or halogen; and R.sub.7 is lower alkyl or hydrogen and the pharmaceutically acceptable salts and N-oxides thereof.Also presented are processes to produce the above compounds and intermediates therefor and derivatives thereof.

摘要翻译： 公开了化学式为“IMAGE”和“IMAGE”，其中R 1是氢，卤素或三氟甲基; R2选自低级烷硫基及其亚砜和砜，卤素，低级烷基氨基或低级烷氧基; Y是氧代或硫代; R 3选自氢，-COOR 4，其中R 4是氢或低级烷基，-CONR 6 R 5，其中R 5和R 6是氢或低级烷基; X是氢或卤素; 并且R 7为低级烷基或氢及其药学上可接受的盐和N-氧化物。

公开(公告)号：US4111931A

公开(公告)日：1978-09-05

申请号：US874074

申请日：1978-02-01

申请人： Armin Walser ,  Rodney Ian Fryer

发明人： Armin Walser ,  Rodney Ian Fryer

IPC分类号： A61K31/55 ,  A61P21/02 ,  A61P25/20 ,  C07D243/12 ,  C07D487/04

CPC分类号： C07D487/04 ,  C07D243/12 ,  Y10S514/906

摘要： The present invention concerns compounds of the formula ##STR1## wherein X is hydrogen or halogen; R.sub.1 is hydrogen, halogen or trifluoromethyl; R.sub.2 is hydrogen or lower alkyl; and R.sub.3 is hydrogen, --COO lower alkyl or CON(R.sub.4).sub.2 wherein R.sub.2 is lower alkyl or hydrogen and may be differentand the pharmaceutically acceptable salts thereof.Also provided are methods for the preparation of these compounds as well as pharmaceutical formulations which contain the active compounds of this invention. The compounds of the formula illustrated above are useful as anxiolytics, anticonvulsants, muscle relaxants and sedative agents.

公开(公告)号：US3970664A

公开(公告)日：1976-07-20

申请号：US540626

申请日：1975-01-13

申请人： Leo Henryk Sternbach ,  Armin Walser

发明人： Leo Henryk Sternbach ,  Armin Walser

IPC分类号： C07D243/20 ,  C07D401/04 ,  C07D487/04

CPC分类号： C07D243/20 ,  C07D401/04 ,  C07D487/04

摘要： Novel preparations of triazolobenzodiazepines are disclosed. Novel 6-pyridyl-4H-triazolo[4,3-a]-1,4-benzodiazepines and novel intermediates are also disclosed which are useful as anticonvulsants, muscle relaxants and sedative agents.

摘要翻译： 公开了三唑并苯并二氮杂类的新型制剂。 还公开了新颖的6-吡啶基-4H-三唑并[4,3-a] -1,4-苯并二氮杂和新的中间体，其可用作抗惊厥药，肌肉松弛剂和镇静剂。

公开(公告)号：US3954838A

公开(公告)日：1976-05-04

申请号：US501585

申请日：1974-08-29

申请人： Joseph Hellerbach ,  Armin Walser ,  Hermann Bretschneider ,  Werner Rudolph

发明人： Joseph Hellerbach ,  Armin Walser ,  Hermann Bretschneider ,  Werner Rudolph

IPC分类号： C07C271/06 ,  C07D243/24 ,  C07C125/06

CPC分类号： C07D243/24 ,  C07C271/06 ,  Y10S514/906

摘要： 1,4-Benzodiazepin-2-ones bearing an acylamidoalkyl-substituent in the 1-position and methods for the preparation thereof are disclosed. These 1,4-benzodiazepin-2-ones exhibit sedative, anti-convulsant and muscle relaxant activity.

摘要翻译： 公开了1位含有酰氨基烷基取代基的1,4-苯并二氮杂-2-酮及其制备方法。 这些1,4-苯并二氮杂-2-酮显示镇静，抗惊厥和肌肉松弛剂活性。

公开(公告)号：US3954753A

公开(公告)日：1976-05-04

申请号：US549566

申请日：1975-02-13

申请人： George Francis Field ,  Leo Henryk Sternbach ,  Armin Walser

发明人： George Francis Field ,  Leo Henryk Sternbach ,  Armin Walser

IPC分类号： C07D241/20 ,  C07D401/06 ,  C07D403/06 ,  C07D487/04 ,  C07D241/14

CPC分类号： C07D401/06 ,  C07D241/20 ,  C07D403/06 ,  C07D487/04

摘要： Novel pyrazino-1,4-diazepines are disclosed together with processes for their preparation and novel intermediates used in these processes. These novel diazepines are useful as sedatives, muscle-relaxants and anti-convulsants.

摘要翻译： 公开了新的吡嗪-1,4-二氮杂及其制备方法和用于这些方法的新型中间体。 这些新的二氮杂类药物可用作镇静剂，肌肉松弛剂和抗惊厥药。