(11aS)-6-methyl-1,2,3,10,11,11a-hexahydro-5H-pyrrolo<2.1-c><1,4>benzodiazepine-5,11-dione | 78756-21-5

• 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: (11aS)-6-methyl-1,2,3,10,11,11a-hexahydro-5H-pyrrolo<2.1-c><1,4>benzodiazepine-5,11-dione
• 英文别名: 6-methylpyrrolobenzodiazepine-5,11-dione；(S)-1,2,3,11a-tetrahydro-6-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-(10H)-dione；(S)-1,2,3,11a-tetrahydro-6-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H)-dione；(6aS)-1-methyl-6a,7,8,9-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-6,11-dione
• CAS: 78756-21-5
• 化学式: C₁₃H₁₄N₂O₂
• 分子量: 230.266
• InChiKey: DKTYBWNZGMFDNC-JTQLQIEISA-N

物化性质

• 熔点：
  207-208 °C
• 沸点：
  488.9±45.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (11aS)-6-methyl-1,2,3,10,11,11a-hexahydro-5H-pyrrolo<2.1-c><1,4>benzodiazepine-5,11-dione 在 正丁基锂 、 硫酸 、 三乙胺 、 叔丁醇 作用下， 以 甲醇 为溶剂， 反应 40.17h， 生成 methyl (1S,2S,6S)-2-[(4-methylphenyl)sulfonylamino]-6-propylcyclohexane-1-carboxylate
  参考文献：
  名称：

  Enantioselective total synthesis of (+)-perhydro-219A from an anthranilic acid derivative

  摘要：

  DOI：

  10.1021/jo00242a007
• 作为产物：
  描述：

  5-甲基-2H-3,1-苯并恶嗪-2,4(1H)-二酮 、 DL-脯氨酸 以73%的产率得到
  参考文献：
  名称：

  SCHULTZ, ARTHUR G.;MCCLOSKEY, PATRICK J.;COURT, JOHN J., J. AMER. CHEM. SOC., 109,(1987) N 21, 6493-6502

  摘要：

  DOI：

文献信息

• A Concise Building Block Approachto a Diverse Multi-Arrayed Library of the Circumdatin Family ofNatural Products
  作者：Andrew Thomas、Alfred Grieder

  DOI：10.1055/s-2003-40870

  日期：2003.8

  Using a polymer-supported phosphine-mediated intramolecular aza-Wittig reaction in a key step of a reaction sequence a diverse library of benzodiazepine-quinazolinone alkaloids (Circumdatins) has been prepared using a novel modified Eguchi protocol. The multi-arrayed library generation strategy commenced from readily accessible benzodiazepinedione derivatives (and anthranilic acids) and all library members were purified by reverse phase preparative HPLC.

  使用聚合物支持的膦介导的分子内氮杂维蒂希反应，在反应序列的关键步骤中，采用一种新型改良的Eguchi协议制备了一系列多样化的苯二氮杂氮烷-喹唑啉酮生物碱（Circumdatins）。多元化库的生成策略从易于获取的苯二氮杂双酮衍生物（和氨基苯甲酸）开始，所有库成员均通过反相制备HPLC进行纯化。
• Oxadiazolyl imidazobenzodiazepine derivatives pharmaceutical
  申请人：A/S Ferrosan

  公开号：US04670433A1

  公开（公告）日：1987-06-02

  New oxadiazolyl imidazobenzodiazepine derivatives having the formula ##STR1## wherein R.sup.3 has the formula ##STR2## wherein R" is hydrogen, C.sub.1-6 alkyl C.sub.1-6 alkoxymethyl or C.sub.3-6 - cycloalkyl; R.sup.4 is hydrogen; R.sup.5 is C.sub.1-6 alkyl or R.sup.4 and R.sup.5 together form a 2-4 membered alkylene bridge; and R.sup.A is C.sub.1-6 alkyl, C.sub.1-6 alkoxy, or C.sub.1-3 trifluoroalkyl, pharmaceutical compositions thereof, and method of treating therewith, are disclosed. The compounds and pharmaceutical compositions are useful in the amelioration, mitigation, or elimination of central nervous system disorders related to benzodiazepine receptors and especially as anticonvulsants, anxiolytics, hypnotics, and nootropics.

  本发明涉及新的噁唑啉基咪唑苯二氮平衍生物，其具有以下式子：##STR1## 其中R.sup.3的式子为：##STR2## 其中R"为氢、C.sub.1-6烷基、C.sub.1-6烷氧甲基或C.sub.3-6环烷基；R.sup.4为氢；R.sup.5为C.sub.1-6烷基或R.sup.4和R.sup.5一起形成2-4元环烷基；R.sup.A为C.sub.1-6烷基、C.sub.1-6烷氧基或C.sub.1-3三氟烷基。本发明还公开了这些化合物和药物组合物，以及使用它们治疗中枢神经系统疾病的方法，特别是作为抗惊厥、抗焦虑、催眠和脑力兴奋剂。
• Oxadiazolyl intermediates
  申请人：A/S Ferrosan

  公开号：US04727153A1

  公开（公告）日：1988-02-23

  New oxadiazolyl imidazobenzodiazepine derivatives having the formula ##STR1## wherein R.sup.3 has the formula ##STR2## wherein R" is hydrogen, C.sub.1-6 alkyl C.sub.1-6 alkoxymethyl or C.sub.3-6 -cycloalkyl; R.sup.4 is hydrogen; R.sup.5 is C.sub.1-6 alkyl or R.sup.4 and R.sup.5 together form a 2-4 membered alkylene bridge; and R.sup.A is C.sub.1-6 alkyl, C.sub.1-6 alkoxy, or C.sub.1-3 trifluoroalkyl, pharmaceutical compositions thereof, and method of treating therewith, are disclosed. The compounds and pharmaceutical compositions are useful in the amelioration, mitigation, or elimination of central nervous system disorders related to benzodiazepine receptors and especially as anticonvulsants, anxiolytics, hypnotics, and nootropics.

  公开了具有以下式子的新的氧代二唑咪唑苯二氮平衍生物：##STR1## 其中R.sup.3具有以下式子：##STR2## 其中R"是氢，C.sub.1-6烷基，C.sub.1-6烷氧甲基或C.sub.3-6环烷基；R.sup.4是氢；R.sup.5是C.sub.1-6烷基或R.sup.4和R.sup.5共同形成2-4成员的烷基桥；以及R.sup.A是C.sub.1-6烷基，C.sub.1-6烷氧基或C.sub.1-3三氟烷基，其制药组合物和治疗方法。这些化合物和制药组合物在改善、缓解或消除与苯二氮平受体相关的中枢神经系统疾病方面有用，特别是作为抗癫痫药、抗焦虑药、催眠药和脑力药。
• Oxadiazolyl imidazobenzodiazepine process
  申请人：A/S Ferrosan

  公开号：US04772696A1

  公开（公告）日：1988-09-20

  New oxadiazolyl imidazobenzodiazepine derivatives having the formula ##STR1## wherein R.sup.3 has the formula ##STR2## wherein R" is hydrogen, C.sub.1-6 alkyl C.sub.1-6 alkoxymethyl or C.sub.3-6 -cycloalkyl; R.sup.4 is hydrogen; R.sup.5 is C.sub.1-6 alkyl or R.sup.4 and R.sup.5 together form a 2-4 membered alkylene bridge; and R.sup.A is C.sub.1-6 alkyl, C.sub.1-6 alkoxy, or C.sub.1-3 trifluoroalkyl, pharmaceutical compositions thereof, and method of treating therewith, are disclosed. The compounds and pharmaceutical compositions are useful in the amelioration, mitigation, or elimination of central nervous system disorders related to benzodiazepine receptors and especially as anticonvulsants, anxiolytics, hypnotics, and nootropics.

  公开了具有以下式子的新的氧代二唑咪唑苯二氮平衍生物：##STR1##其中R.sup.3具有以下式子：##STR2##其中R"是氢，C.sub.1-6烷基，C.sub.1-6烷氧甲基或C.sub.3-6环烷基；R.sup.4是氢；R.sup.5是C.sub.1-6烷基或R.sup.4和R.sup.5一起形成2-4个成员的烷基桥；R.sup.A是C.sub.1-6烷基，C.sub.1-6烷氧基或C.sub.1-3三氟甲基，以及它们的药物组成物和治疗方法。这些化合物和药物组成物在改善、缓解或消除与苯二氮平受体相关的中枢神经系统疾病，特别是作为抗惊厥、抗焦虑、催眠和脑力兴奋剂方面是有用的。
• Imidazodiazepine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US04346030A1

  公开（公告）日：1982-08-24

  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.

  公式为##STR1##的咪唑二氮杂苯并二氮杂环衍生物，其中A与表示为α和β的两个碳原子一起从以下组中选择：##STR2##虚线表示(a)和(b)中存在的双键，D是>C.dbd.O或>C.dbd.S，R.sup.1从以下组中选择：氰基，低烷酰基和公式--COOR.sup.4的基团，R.sup.4从甲基，乙基，异丙基和2-羟乙基的组中选择，R.sup.5从氢，三氟甲基和卤素的组中选择，R.sup.6从氢，三氟甲基，卤素和低烷基的组中选择，R.sup.2要么是氢，R.sup.3是氢或低烷基，要么R.sup.2和R.sup.3一起是三亚甲基或丙烯亚甲基，表示为γ的碳原子具有S-或R，S-构型，以及其药学上可接受的盐。它们有用于拮抗具有镇静作用的1,4-苯二氮䓬类药物的中枢抑制，肌肉松弛，共济失调，降压和呼吸抑制特性。例如，它们可以用作中毒的解毒剂，在这种情况下，过量摄入具有镇静作用的1,4-苯二氮䓬类药物，或用于缩短由这些1,4-苯二氮䓬类药物引起的麻醉。它们还可以用于抑制在其他适应症领域使用的1,4-苯二氮䓬类药物对中枢神经系统的活性，例如对血吸虫活性的1,4-苯二氮䓬类药物，例如(+)-5-(o-氯苯基)-1,3-二氢-3-甲基-7-硝基-2H-1,4-苯二氮䓬啶-2-酮。还提供了生产咪唑二氮杂苯并二氮杂环衍生物及其中间体的过程。