(11aR)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo-<2,1-c><1,4>benzodiazepin-5-one | 214143-90-5

• 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: (11aR)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo-<2,1-c><1,4>benzodiazepin-5-one
• 英文别名: (11AR)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one；(6aR)-5,6,6a,7,8,9-hexahydropyrrolo[2,1-c][1,4]benzodiazepin-11-one
• CAS: 214143-90-5
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: HYPFMFLAOOULNZ-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (11aR)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo-<2,1-c><1,4>benzodiazepin-5-one 以89.5%的产率得到(11aR)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo-<2,1-c><1,4>benzodiazepine
  参考文献：
  名称：

  Biphenyl derivatives and drug composition

  摘要：

  由以下一般式（1）表示的联苯衍生物和其药学上可接受的盐：[在式（1）中，A代表单键，—CH2—，—CO—，—CS—或—SO2—；B代表单键或—CH2—；R1代表氢原子，—OH，—NR11R12（其中R11和R12各自独立地代表一个氢原子或具有1至4个碳原子的烷基基团），—OCOCH3或卤素原子；R2代表氢原子或R1和R2共同形成一个羟基；R3代表氢原子或具有1至4个碳原子的烷基基团；在该式中，位置a的绝对构型可以是R或S]。本发明的化合物具有相当高的安全性和有效性，并且特别适用作为抗利尿激素受体拮抗剂。

  公开号：

  US06225306B1
• 作为产物：
  描述：

  (11aS)-2,3,5,10,11,11a-hexahydro-1H-pyrrolo<2,1-c><1,4>benzodiazepin-5,11-dione 在 sodium tetrahydroborate 、 三氟乙酸 作用下， 以 乙二醇二甲醚 为溶剂， 反应 4.0h， 以95%的产率得到(11aR)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo-<2,1-c><1,4>benzodiazepin-5-one
  参考文献：
  名称：

  Novel vasopressin V2 receptor-selective antagonists, pyrrolo[2,1-a]quinoxaline and pyrrolo[2,1-c][1,4]benzodiazepine derivatives

  摘要：

  The intent of the work was to study the structure-activity relationships of AVP receptor antagonists bearing a chiral ring as a partial structure since such studies had been reported for only achiral compounds. In the present paper, we deal with compounds consisting of the chiral tricyclic hetero ring (1,2,3,3a,4,5-hexahydropyrrolo[1,2-a]quinoxaline and 1,2,3,10,11,11a-hexahydro- 1H-pyrrolo[2,1-c][1,4]benzodiazepine) and 2-phenylbenzanilide analogues. These compounds exhibited a highly selective affinity for V2 receptor, and their stereochemical configuration had a great influence on V2 receptor binding. VP-343 (N-[4[(2S,3aR)-2-hydroxy-2,3,3a,4-tetrahydropyrrolo[1,2-a]quinoxalin-5 VP-365 (N-[4-[(11aS)-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]phenyl][1,1'-biphenyl]-2-carboxamide)) and VP-339 (N-[4-[(11aS)-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]phenyl]-[1,1'-biphenyl]-2-carboxamide) were the most potent compounds in vitro and in vivo. The IC50 values of VP-343, VP-365 and VP-339 against V2 receptor were 0.772, 1.18 and 0.216 nM, respectively. The ED300 values (dose required to increase three times the urine volume of the control rats; oral administration) of VP-343, VP-365 and VP-339 were 0.22, 0.31 and 0.78 mg/kg, respectively. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00049-8

文献信息

• BIPHENYL DERIVATIVES AND MEDICINAL COMPOSITIONS
  申请人：Wakamoto Pharmaceutical Co., Ltd.

  公开号：EP0987266A1

  公开（公告）日：2000-03-22

  A biphenyl derivative represented by the following general formula (1) and a pharmaceutically acceptable salt thereof: [In the formula (1), A represents a single bond, -CH2-, -CO-, -CS- or -SO2-; B represents a single bond or -CH2-; R1 represents a hydrogen atom, -OH, -NR11R12 (wherein R11 and R12 each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms), -OCOCH3, or a halogen atom; R2 represents a hydrogen atom or R1 and R2 form a group =O together; R3 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; provided that in the formula, the absolute configuration of the position a may be either R or S]. The compound of the present invention has considerably high safety and efficacy and is useful as, in particular, a vasopressin receptor antagonist.

  由以下通式(1)代表的联苯衍生物及其药学上可接受的盐： [在式(1)中，A代表单键、-CH2-、-CO-、-CS-或-SO2-；B代表单键或-CH2-；R1代表氢原子、-OH、-NR11R12（其中R11和R12各自独立地代表氢原子或具有1至4个碳原子的烷基）、-OCOCH3或卤素原子；R2 代表氢原子或 R1 和 R2 共同形成一个基团 =O；R3 代表氢原子或具有 1 至 4 个碳原子的烷基；但在式中，a 位的绝对构型可以是 R 或 S]。本发明的化合物具有相当高的安全性和有效性，尤其可用作血管加压素受体拮抗剂。
• Novel vasopressin V2 receptor-selective antagonists, pyrrolo[2,1-a]quinoxaline and pyrrolo[2,1-c][1,4]benzodiazepine derivatives
  作者：Yasuhiro Ohtake、Akira Naito、Hisashi Hasegawa、Katsuhiro Kawano、Daisuke Morizono、Makoto Taniguchi、Yoko Tanaka、Hidehiko Matsukawa、Kenji Naito、Touru Oguma、Yohji Ezure、Yoshihiro Tsuriya

  DOI：10.1016/s0968-0896(99)00049-8

  日期：1999.6

  The intent of the work was to study the structure-activity relationships of AVP receptor antagonists bearing a chiral ring as a partial structure since such studies had been reported for only achiral compounds. In the present paper, we deal with compounds consisting of the chiral tricyclic hetero ring (1,2,3,3a,4,5-hexahydropyrrolo[1,2-a]quinoxaline and 1,2,3,10,11,11a-hexahydro- 1H-pyrrolo[2,1-c][1,4]benzodiazepine) and 2-phenylbenzanilide analogues. These compounds exhibited a highly selective affinity for V2 receptor, and their stereochemical configuration had a great influence on V2 receptor binding. VP-343 (N-[4[(2S,3aR)-2-hydroxy-2,3,3a,4-tetrahydropyrrolo[1,2-a]quinoxalin-5 VP-365 (N-[4-[(11aS)-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]phenyl][1,1'-biphenyl]-2-carboxamide)) and VP-339 (N-[4-[(11aS)-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]phenyl]-[1,1'-biphenyl]-2-carboxamide) were the most potent compounds in vitro and in vivo. The IC50 values of VP-343, VP-365 and VP-339 against V2 receptor were 0.772, 1.18 and 0.216 nM, respectively. The ED300 values (dose required to increase three times the urine volume of the control rats; oral administration) of VP-343, VP-365 and VP-339 were 0.22, 0.31 and 0.78 mg/kg, respectively. (C) 1999 Elsevier Science Ltd. All rights reserved.
• US6225306B1
  申请人：——

  公开号：US6225306B1

  公开（公告）日：2001-05-01
• Identification of the benzodiazepines as a new class of antileishmanial agent
  作者：Rachel L. Clark、Katharine C. Carter、Alexander B. Mullen、Geoffrey D. Coxon、George Owusu-Dapaah、Emma McFarlane、M. Dao Duong Thi、M. Helen Grant、Justice N.A. Tettey、Simon P. Mackay

  DOI：10.1016/j.bmcl.2006.11.004

  日期：2007.2

  The continual increase in drug resistance; the lack of new chemotherapeutic agents; the toxicity of existing agents and the increasing morbidity with HIV co-infection mean the search for new antileishmanial agents has never been more urgent. We have identified the benzodiazepines as a structural class for antileishmanial hit optimisation, and demonstrated that their in vitro activity is comparable with the clinically used drug, sodium stibogluconate, and that the compounds are not toxic to macrophages. (c) 2006 Elsevier Ltd. All rights reserved.
• Biphenyl derivatives and drug composition
  申请人：Wakamoto Pharmaceutical Co., Ltd.

  公开号：US06225306B1

  公开（公告）日：2001-05-01

  A biphenyl derivative represented by the following general formula (1) and a pharmaceutically acceptable salt thereof: [In the formula (1), A represents a single bond, —CH2—, —CO—, —CS— or —SO2—; B represents a single bond or —CH2—; R1 represents a hydrogen atom, —OH, —NR11R12 (wherein R11 and R12 each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms), —OCOCH3, or a halogen atom; R2 represents a hydrogen atom or R1 and R2 form a group ═O together; R3 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; provided that in the formula, the absolute configuration of the position a may be either R or S]. The compound of the present invention has considerably high safety and efficacy and is useful as, in particular, a vasopressin receptor antagonist.

  由以下一般式（1）表示的联苯衍生物和其药学上可接受的盐：[在式（1）中，A代表单键，—CH2—，—CO—，—CS—或—SO2—；B代表单键或—CH2—；R1代表氢原子，—OH，—NR11R12（其中R11和R12各自独立地代表一个氢原子或具有1至4个碳原子的烷基基团），—OCOCH3或卤素原子；R2代表氢原子或R1和R2共同形成一个羟基；R3代表氢原子或具有1至4个碳原子的烷基基团；在该式中，位置a的绝对构型可以是R或S]。本发明的化合物具有相当高的安全性和有效性，并且特别适用作为抗利尿激素受体拮抗剂。