ethyl (S)-(+)-7-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: ethyl (S)-(+)-7-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate
• 英文别名: Ro 14-5975；Ethyl (S)-(+)-7-chlor-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate；ethyl (S)-7-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate；(S)-(+)-ethyl-7-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate；ethyl (7S)-15-chloro-12-oxo-2,4,11-triazatetracyclo[11.4.0.02,6.07,11]heptadeca-1(17),3,5,13,15-pentaene-5-carboxylate
• 化学式: C₁₇H₁₆ClN₃O₃
• 分子量: 345.785
• InChiKey: GXXNSEYTZVNYNW-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (S)-(+)-7-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate 、 羟甲基环丙烷 在 Tetraethyl orthotitanate 盐酸 、 氯仿 、 碳酸氢钠 、 magnesium sulfate 、 乙酸乙酯 作用下， 反应 16.33h， 以there is obtained cyclopropylmethyl (S)-7-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate of melting point 146°-148°的产率得到cyclopropylmethyl (S)-7-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate
  参考文献：
  名称：

  Imidazobenzodiazepines

  摘要：

  本文描述了一种新型药物活性物质，其对中枢苯二氮平受体具有显著的亲和力，且毒性较低。这些活性物质是公式I中的咪唑苯二氮平，其中A为较低的烷基，n为零或1，R1为较低的炔基、较低的烯基、芳基、(C3-8)-环烷基（可选地被较低的烷基取代）或(C5-8)-环烯基（可选地被较低的烷基取代）、或含有氧或硫原子作为环成员的5-或6-成员饱和或不饱和杂环，且可选地被较低的烷基取代，R4和R5分别为氢、卤素、三氟甲基、氰基、硝基、氨基或较低的烷基，而R2为氢且R3为较低的烷基或R2和R3一起为二甲亚烷、三甲亚烷或丙烯亚烷，公式I中R2和R3一起为二甲亚烷、三甲亚烷或丙烯亚烷的化合物相对于被标记为γ的碳原子具有(S)或(R,S)构型，它们的药学上可接受的酸盐加合物可以作为药物制剂使用，特别是在控制惊厥和焦虑状态和/或部分或完全拮抗一些或所有1,4-苯二氮平具有镇静作用或其他物质通过中枢苯二氮平受体显示的活性方面。

  公开号：

  US04489003A1
• 作为产物：
  描述：

  异氰基乙酸乙酯 、 potassium tert-butylate 、 氯磷酸二乙酯 、 (S)-7-chloro-2,3-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)-dione 在 溶剂黄146 作用下， 以 N-甲基乙酰胺 、 水 、 乙酸乙酯 为溶剂， 生成 ethyl (S)-(+)-7-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate
  参考文献：
  名称：

  Imidazodiazepine derivatives

  摘要：

  咪唑二氮杂环己烯衍生物的公式为##STR1##其中A与两个碳原子α和β一起从##STR2##中选择，虚线代表(a)和(b)中存在的双键，D为>C.dbd.O或>C.dbd.S，R.sup.1从氰基，较低的烷酰基和公式--COOR.sup.4的基团中选择，R.sup.4从甲基，乙基，异丙基和2-羟乙基中选择，R.sup.5从氢，三氟甲基和卤素中选择，R.sup.6从氢，三氟甲基，卤素和较低烷基中选择，R.sup.2为氢，R.sup.3为氢或较低烷基，或者R.sup.2和R.sup.3一起为三甲亚基或丙烯亚基，所述的碳原子γ具有S-或R,S-构型，及其药学上可接受的盐，用于对抗具有镇静活性的1,4-苯二氮杂环己烷的中枢抑制、肌肉松弛、共济失调、降低血压和呼吸抑制特性。它们可以用作例如，在过量摄入具有镇静活性的1,4-苯二氮杂环己烷的中毒情况下的解毒剂，或者缩短由这些1,4-苯二氮杂环己烷引起的麻醉。它们还可用于抑制其他适应领域中使用的1,4-苯二氮杂环己烷对中枢神经系统的活性，例如对于片尾蚴活性的1,4-苯二氮杂环己烷，如(+)-5-(邻氯苯基)-1,3-二氢-3-甲基-7-硝基-2H-1,4-苯二氮杂环己烷-2-酮。还提供了生产咪唑二氮杂环己烯衍生物及其中间体的方法。

  公开号：

  US04316839A1

文献信息

• Diazepine derivatives and their use
  申请人：Hoffmann-La Roche Inc.

  公开号：US04352818A1

  公开（公告）日：1982-10-05

  There is presented imidazodiazepines of the formula ##STR1## wherein A together with the two carbon atoms denoted as .alpha. and .beta. is the group ##STR2## R.sup.1 is hydrogen, lower alkyl, lower alkoxymethyl, halogen or nitro, R.sup.4 is hydrogen, trifluoromethyl or halogen, R.sup.5 is hydrogen, fluoromethyl, halogen or lower alkyl and X is an oxygen or sulphur atom, and either R.sup.2 is hydrogen and R.sup.3 is 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 their pharmaceutically acceptable acid addition salts. The compounds antagonize the central-depressant, muscle relaxant, ataxic, blood pressure-lowering and respiratory-depressant properties of 1,4-benzodiazepines which have tranquillizing activity. Thus they can be used, for example, as antidotes in the case of intoxications with 1,4-benzodiazepines which have tranquillizing activity. Also presented are various methods to produce the imidazodiazepine derivatives.

  提供了公式为##STR1##的咪唑二氮平类化合物，其中A与标记为α和β的两个碳原子一起是##STR2##，R.sup.1是氢、低烷基、低烷氧甲基、卤素或硝基，R.sup.4是氢、三氟甲基或卤素，R.sup.5是氢、氟甲基、卤素或低烷基，X是氧或硫原子，R.sup.2要么是氢，R.sup.3是低烷基，要么R.sup.2和R.sup.3一起是三亚甲基或丙烯亚甲基，标记为γ的碳原子具有(S)-或(R,S)-构型，并且它们的药学上可接受的酸盐也被提供。这些化合物对具有镇静活性的1,4-苯二氮平的中枢抑制、肌肉松弛、共济失调、降压和呼吸抑制特性具有拮抗作用。因此，它们可以用作例如在1,4-苯二氮平有镇静作用的中毒情况下的解毒剂。还提供了各种制备咪唑二氮平衍生物的方法。
• US4352818A
  申请人：——

  公开号：US4352818A

  公开（公告）日：1982-10-05
• Imidazobenzodiazepines
  申请人：Hoffmann-La Roche Inc.

  公开号：US04489003A1

  公开（公告）日：1984-12-18

  There are described novel pharmaceutically active substances which have a pronounced affinity to the central benzodiazepine receptors and which have only a low toxicity. These active substances, namely imidazobenzodiazepines of the formula ##STR1## wherein A is lower alkylene, n is zero or 1, R.sup.1 is lower alkynyl, lower alkenyl, aryl, (C.sub.3-8)-cycloalkyl optionally substituted by lower alkyl or (C.sub.5-8)-cycloalkenyl optionally substituted by lower alkyl, or a 5- or 6-membered saturated or unsaturated heterocycle which contains an oxygen or sulphur atom as a ring member and which is optionally substituted by lower alkyl, R.sup.4 and R.sup.5 each are hydrogen, halogen, trifluoromethyl, cyano, nitro, amino or lower alkyl and either R.sup.2 is hydrogen and R.sup.3 is lower alkyl or R.sup.2 and R.sup.3 together are dimethylene, trimethylene or propenylene, the compounds of formula I in which R.sup.2 and R.sup.3 together are dimethylene, trimethylene or propenylene having the (S) or (R,S) configuration with reference to the carbon atom denoted by .gamma., and their pharmaceutically acceptable acid addition salts, can be used as medicaments in the form of pharmaceutical preparations, especially in the control of convulsions and anxiety states and/or in the partial or complete antagonization of some or all activities which 1,4-benzodiazepines having tranquillizing activity or other substances display via the central benzodiazepine receptors.

  描述了一种新型具有显著亲和力的药用活性物质，它们对中枢苯二氮卓类受体具有高亲和力，且毒性低。这些活性物质，即具有以下结构的咪唑苯二氮卓类化合物：其中A为较低的烷基，n为零或1，R1为较低的炔基、较低的烯基、芳基、(C3-8)-环烷基（可选择地被较低的烷基取代）或(C5-8)-环烯烷基（可选择地被较低的烷基取代），或者是含有氧或硫原子作为环成员的5-或6-成员饱和或不饱和杂环，且可选择地被较低的烷基取代，R4和R5各自为氢、卤素、三氟甲基、氰基、硝基、氨基或较低的烷基，而R2为氢且R3为较低的烷基，或者R2和R3一起为二甲亚乙烷、三甲亚乙烷或丙烯亚乙烷，其中R2和R3一起为二甲亚乙烷、三甲亚乙烷或丙烯亚乙烷的具有对应于由γ表示的碳原子的(S)或(R,S)构型的I式化合物，以及它们的药学上可接受的酸盐加合物，可作为药物用于制备药物制剂，特别用于控制癫痫和焦虑状态，或者部分或完全拮抗一些或全部1,4-苯二氮卓类具有镇静作用或其他物质通过中枢苯二氮卓类受体表现出的活性。
• Imidazodiazepine derivatives
  申请人：Hoffman-La Roche Inc.

  公开号：US04316839A1

  公开（公告）日：1982-02-23

  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.

  咪唑二氮杂环己烯衍生物的公式为##STR1##其中A与两个碳原子α和β一起从##STR2##中选择，虚线代表(a)和(b)中存在的双键，D为>C.dbd.O或>C.dbd.S，R.sup.1从氰基，较低的烷酰基和公式--COOR.sup.4的基团中选择，R.sup.4从甲基，乙基，异丙基和2-羟乙基中选择，R.sup.5从氢，三氟甲基和卤素中选择，R.sup.6从氢，三氟甲基，卤素和较低烷基中选择，R.sup.2为氢，R.sup.3为氢或较低烷基，或者R.sup.2和R.sup.3一起为三甲亚基或丙烯亚基，所述的碳原子γ具有S-或R,S-构型，及其药学上可接受的盐，用于对抗具有镇静活性的1,4-苯二氮杂环己烷的中枢抑制、肌肉松弛、共济失调、降低血压和呼吸抑制特性。它们可以用作例如，在过量摄入具有镇静活性的1,4-苯二氮杂环己烷的中毒情况下的解毒剂，或者缩短由这些1,4-苯二氮杂环己烷引起的麻醉。它们还可用于抑制其他适应领域中使用的1,4-苯二氮杂环己烷对中枢神经系统的活性，例如对于片尾蚴活性的1,4-苯二氮杂环己烷，如(+)-5-(邻氯苯基)-1,3-二氢-3-甲基-7-硝基-2H-1,4-苯二氮杂环己烷-2-酮。还提供了生产咪唑二氮杂环己烯衍生物及其中间体的方法。