公开(公告)号：US4546183A

公开(公告)日：1985-10-08

申请号：US643509

申请日：1984-08-23

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 ,  C07C45/71 ,  C07C65/34 ,  C07D209/48 ,  C07D223/16 ,  C07D239/42 ,  C07D317/16 ,  C07D317/30 ,  C07D487/04 ,  C07D211/70

CPC分类号： C07D209/48 ,  C07C45/63 ,  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 di-lower 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，基团NR 4 R 5，基团-CH 2 -CO-R7，基团-NH（CH2）mNR8R9，羟基，低级烷氧基，巯基和低级烷基巯基; R2选自氢，氨基和二低级烷基氨基; 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，或基团为-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。 还提出了生产上述最终产品的各种新型中间体和方法。

公开(公告)号：US4973599A

公开(公告)日：1990-11-27

申请号：US323583

申请日：1989-03-14

申请人： Norman W. Gilman ,  Wen Y. Chen

发明人： Norman W. Gilman ,  Wen Y. Chen

IPC分类号： C07D233/84 ,  C07D239/38 ,  C07D277/36

CPC分类号： C07D239/38 ,  C07D233/84 ,  C07D277/36

摘要： Compounds of the formula ##STR1## wherein n is a integer of 0 to 2; R.sub.1 ' and R.sub.2 ' are, independently, hydrogen, halogen, trifluoromethyl, lower alkoxy or lower alkyl; and X is pyrimidinyl, thiazolyl or ##STR2## wherein R is hydrogen, lower alkyl, aryl or ar-lower alkyl; provided that at least one or R.sub.1 ' and R.sub.2 ' is other than hydrogen,and their pharmaceutically acceptable acid addition salts, and an anti-inflammatory method utilizing a compound of the formula ##STR3## wherein n is an integer of 0 to 2; R.sub.1 and R.sub.2 are, independently, hydrogen, halogen, trifluoromethyl, nitro, amino, lower alkylamino, di-lower-alkylamino, lower alkoxy or lower alkyl; and X is pyrimidinyl, thiazolyl or ##STR4## wherein R is hydrogen, lower alkyl, aryl or ar-lower alkyl; and their pharmaceutically acceptable acid addition salts, are described.

摘要翻译： 式（Ⅰ）化合物其中n为0〜2的整数; R1'和R2'独立地为氢，卤素，三氟甲基，低级烷氧基或低级烷基; 并且X是嘧啶基，噻唑基或者其中R是氢，低级烷基，芳基或芳 - 低级烷基; 条件是至少一个或R 1'和R 2'不是氢，以及它们的药学上可接受的酸加成盐，以及利用式II的化合物的抗炎方法，其中n是0-2的整数; R 1和R 2独立地是氢，卤素，三氟甲基，硝基，氨基，低级烷基氨基，二低级烷基氨基，低级烷氧基或低级烷基; 并且X是嘧啶基，噻唑基或者其中R是氢，低级烷基，芳基或芳 - 低级烷基; 及其药学上可接受的酸加成盐。

公开(公告)号：US4269774A

公开(公告)日：1981-05-26

申请号：US161713

申请日：1980-06-23

申请人： Rodney I. Fryer ,  Norman W. Gilman

发明人： Rodney I. Fryer ,  Norman W. Gilman

IPC分类号： C07D209/50 ,  C07D513/04 ,  A61K31/55

CPC分类号： C07D513/04 ,  C07D209/50

摘要： There is presented compounds of formula ##STR1## wherein X and Y are hydrogen or halogen and R.sub.1 is lower alkyl or NR.sub.2 R.sub.3wherein R.sub.2 and R.sub.3 are hydrogen or lower alkyland the pharmaceutically acceptable salts thereof.Also presented are novel intermediates and a process to produce the novel end products.The compounds of formula I are useful as anxiolytic and sedative agents.

摘要翻译： 提供式Ⅰ的化合物，其中X和Y是氢或卤素，R 1是低级烷基或NR 2 R 3，其中R 2和R 3是氢或低级烷基及其可药用的盐。 还提出了新型中间体和生产新型终产物的方法。 式I的化合物可用作抗焦虑剂和镇静剂。

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：US4321199A

公开(公告)日：1982-03-23

申请号：US216059

申请日：1980-12-15

申请人： Rodney I. Fryer ,  Norman W. Gilman

发明人： Rodney I. Fryer ,  Norman W. Gilman

IPC分类号： C07D209/50 ,  C07D513/04 ,  C07D209/48 ,  A61K31/425 ,  C07D417/06

CPC分类号： C07D513/04 ,  C07D209/50

摘要： There is presented compounds of formula ##STR1## wherein X and Y are hydrogen or halogen and R.sub.1 is lower alkyl or NR.sub.2 R.sub.3wherein R.sub.2 and R.sub.3 are hydrogen or lower alkyland the pharmaceutically acceptable salts thereof.Also presented are novel intermediates and a process to produce the novel end products.The compounds of formula I are useful as anxiolytic and sedative agents.

摘要翻译： 提供式Ⅰ的化合物，其中X和Y是氢或卤素，R 1是低级烷基或NR 2 R 3，其中R 2和R 3是氢或低级烷基及其可药用的盐。 还提出了新型中间体和生产新型终产物的方法。 式I的化合物可用作抗焦虑剂和镇静剂。

公开(公告)号：US5428004A

公开(公告)日：1995-06-27

申请号：US164084

申请日：1993-12-08

申请人： James V. Earley ,  Norman W. Gilman ,  Perry Rosen

发明人： James V. Earley ,  Norman W. Gilman ,  Perry Rosen

IPC分类号： A61K31/55 ,  A61P7/02 ,  A61P11/00 ,  A61P37/00 ,  A61P37/08 ,  C07D495/14

CPC分类号： C07D495/14

摘要： The invention relates to compounds of the formula ##STR1## wherein R.sub.1 is OR.sub.6 or NHR.sub.7, R.sub.6 and R.sub.7, which may be, the same or different, are hydrogen, lower alkyl, lower alkenyl, cycloalkyl having between 3 to 6 carbon atoms or phenyl, R.sub.2 is lower alkyl, lower alkoxy or trifluoromethyl, R.sub.3 and R.sub.4 independently, are hydrogen, chlorine, fluorine, lower alkyl or lower alkoxy, and R.sub.5 is lower alkyl or cycloalkyl having between 3 to 6 carbon atoms, and when at least one asymetric carbon is present, enantiomers, and racemates thereof, and pharmaceutically acceptable salts thereof.The compounds of formula I and pharmaceutically acceptable salts thereof are useful as bronchopulmonary agents for example in the relief of asthma and allergic reactions.In another aspect, the invention relates to pharmaceutical compositions, methods of using the compound of formula I and intermediates.

摘要翻译： 本发明涉及下式化合物其中R 1为OR 6或NHR 7，R 6和R 7可以相同或不同，为氢，低级烷基，低级链烯基，具有3-6个碳原子的环烷基或 苯基，R2是低级烷基，低级烷氧基或三氟甲基，R3和R4 + L独立地是氢，氯，氟，低级烷基或低级烷氧基，R5是具有3-6个碳原子的低级烷基或环烷基，而当 存在至少一种不对称碳，其对映异构体和外消旋体及其药学上可接受的盐。 式I化合物及其药学上可接受的盐可用作例如缓解哮喘和过敏反应的支气管肺动力剂。 另一方面，本发明涉及药物组合物，使用式I化合物和中间体的方法。

公开(公告)号：US4777169A

公开(公告)日：1988-10-11

申请号：US117599

申请日：1987-11-06

申请人： James V. Earley ,  Norman W. Gilman

发明人： James V. Earley ,  Norman W. Gilman

IPC分类号： A61K51/00 ,  C07D243/16 ,  C07D243/18 ,  C07D243/24 ,  C07D243/26 ,  A61K31/55

CPC分类号： C07D243/24

摘要： Benzodiazepine derivatives useful in immunoassays for benzodiazepines.

摘要翻译： 苯并二氮杂衍生物可用于苯并二氮杂卓的免疫测定。

公开(公告)号：US4547581A

公开(公告)日：1985-10-15

申请号：US643563

申请日：1984-08-23

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 ,  C07C291/04 ,  C07C309/66 ,  C07D209/48 ,  C07D223/16 ,  C07D317/00

CPC分类号： C07D209/48 ,  C07C291/04 ,  C07C309/66 ,  C07C45/63 ,  C07C45/68 ,  C07D223/16

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 di-lower 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（a）（b）（c）和（d）R1选自组 由氢，氯，溴，低级烷基，基团NR4R5，基团-CH2-CO-R7，基团-NH（CH2）mNR8R9，羟基，低级烷氧基，巯基和低级烷基巯基组成; R2选自氢，氨基和二低级烷基氨基; 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，或基团为-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。 还提出了生产上述最终产品的各种新型中间体和方法。

公开(公告)号：US5302590A

公开(公告)日：1994-04-12

申请号：US993227

申请日：1992-12-18

申请人： James V. Earley ,  Norman W. Gilman ,  Perry Rosen

发明人： James V. Earley ,  Norman W. Gilman ,  Perry Rosen

IPC分类号： A61K31/55 ,  A61P7/02 ,  A61P11/00 ,  A61P37/00 ,  A61P37/08 ,  C07D495/14

CPC分类号： C07D495/14

摘要： The invention relates to compounds of the formula ##STR1## wherein R.sub.1 is OR.sub.6 or NHR.sub.7, R.sub.6 and R.sub.7, which may be, the same or different, are hydrogen, lower alkyl, lower alkenyl, cycloalkyl having between 3 to 6 carbon atoms or phenyl, R.sub.2 is lower alkyl, lower alkoxy or trifluoromethyl, R.sub.3 and R.sub.4, independently, are hydrogen, chlorine, fluorine, lower alkyl or lower alkoxy, and R.sub.5 is lower alkyl or cycloalkyl having between 3 to 6 carbon atoms, and when at least one asymetric carbon is present, enantiomers, and racemates thereof, and pharmaceutically acceptable salts thereof.The compounds of formula I and pharmaceutically acceptable salts thereof are useful as bronchopulmonary agents for example in the relief of asthma and allergic reactions.In another aspect, the invention relates to pharmaceutical compositions, methods of using the compound of formula I and intermediates.

摘要翻译： 本发明涉及下式化合物其中R 1为OR 6或NHR 7，R 6和R 7可以相同或不同，为氢，低级烷基，低级链烯基，具有3-6个碳原子的环烷基或 苯基，R2是低级烷基，低级烷氧基或三氟甲基，R3和R4独立地是氢，氯，氟，低级烷基或低级烷氧基，R5是具有3-6个碳原子的低级烷基或环烷基，当至少 存在一种不对称碳，其对映异构体和外消旋体及其药学上可接受的盐。 式I化合物及其药学上可接受的盐可用作例如缓解哮喘和过敏反应的支气管肺动力剂。 另一方面，本发明涉及药物组合物，使用式I化合物和中间体的方法。

公开(公告)号：US4336388A

公开(公告)日：1982-06-22

申请号：US216097

申请日：1980-12-15

申请人： Rodney I. Fryer ,  Norman W. Gilman

发明人： Rodney I. Fryer ,  Norman W. Gilman

IPC分类号： C07D209/50 ,  C07D277/42 ,  C07D513/04 ,  C07D417/06

CPC分类号： C07D513/04 ,  C07D209/50

摘要： There is presented compounds of formula ##STR1## wherein X and Y are hydrogen or halogen and R.sub.1 is lower alkyl or NR.sub.2 R.sub.3wherein R.sub.2 and R.sub.3 are hydrogen or lower alkyland the pharmaceutically acceptable salts thereof.Also presented are novel intermediates and a process to produce the novel end products.The compounds of formula I are useful as anxiolytic and sedative agents.

摘要翻译： 提供式Ⅰ的化合物，其中X和Y是氢或卤素，R 1是低级烷基或NR 2 R 3，其中R 2和R 3是氢或低级烷基及其可药用的盐。 还提出了新型中间体和生产新型终产物的方法。 式I的化合物可用作抗焦虑剂和镇静剂。