(S)-(+)-2,3,5,10,11,11a-hexahydro-1H-pyrrolo-<2,1-c><1,4>benzodiazepine | 50424-44-7

• 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: (S)-(+)-2,3,5,10,11,11a-hexahydro-1H-pyrrolo-<2,1-c><1,4>benzodiazepine
• 英文别名: (11aS)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo-<2,1-c><1,4>benzodiazepine；(11AS)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine；(6aS)-6,6a,7,8,9,11-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine
• CAS: 50424-44-7
• 化学式: C₁₂H₁₆N₂
• 分子量: 188.272
• InChiKey: QZLFCLRNSOXWFA-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-(+)-2,3,5,10,11,11a-hexahydro-1H-pyrrolo-<2,1-c><1,4>benzodiazepine 、 4-[(2-苯基苯甲酰基)氨基]苯甲酰氯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以81%的产率得到Biphenyl-2-carboxylic acid [4-((S)-2,3,11,11a-tetrahydro-1H,5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-phenyl]-amide
  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
• 作为产物：
  描述：

  N-(2-硝基苯甲酰基)-L-脯氨酸甲酯 在 lithium aluminium tetrahydride 、 铁粉 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-(+)-2,3,5,10,11,11a-hexahydro-1H-pyrrolo-<2,1-c><1,4>benzodiazepine
  参考文献：
  名称：

  某些新的叔胺的合成及其与l-脯氨酸的助催化剂在邻硝基苯甲醛与甲基乙烯基酮的对映选择性Baylis-Hillman反应中的应用

  摘要：

  由邻硝基苯甲酰氯和1-脯氨酸甲酯盐酸盐开始合成手性苯并二氮杂1衍生物1。非对映异构体（1 R，2 R，1 'S）-（+）-2- [ N-甲基-N-（α-苯乙基）氨基]环己醇3a和（1 S，2 S，1 'S）-（+由（S）-α-苯基乙胺和环己烯氧化物经开环，非对映异构体分离和N-甲基化反应合成））- 2- [ N-甲基-N-（α-苯基乙基）氨基]环己醇3b。（S，由1-脯氨酸甲酯合成S）-八氢二吡咯并[1,2- a：1'，2'- d ]吡嗪5。手性叔胺1，图3a，图3b和5几乎不能催化之间的的Baylis-Hillman反应ö -nitrobenzaldehyde和甲基乙烯基酮（MVK）。然而，它们在1-脯氨酸存在下作为该反应的有效催化剂。以高收率获得相应的加合物，对映选择性分别为83％ee，81％ee，51％ee和66％ee。

  DOI：

  10.1016/j.tetlet.2006.06.023

文献信息

• 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。
• Chiral Tertiary Amine/L-Proline Cocatalyzed Enantioselective Morita–Baylis–Hillman (MBH) Reaction
  作者：Hongying Tang、Guofeng Zhao、Zhenghong Zhou、Peng Gao、Liangnian He、Chuchi Tang

  DOI：10.1002/ejoc.200700794

  日期：2008.1

  cocatalytic reactions with the two enantiomers of chiral amine 4 and L-proline revealed that it is the proline stereochemistry that determines the configuration of the newly formed chiral center. In addition, the existence of the free hydroxy group in amine 4a enhanced the enantioselectivity of the reaction. Based on these findings, a plausible mechanism for this cocatalytic MBH reaction has been proposed

  从容易获得的手性来源开始，已经合成了四种类型的手性胺。已发现这些手性胺与 L-脯氨酸结合是甲基乙烯基酮 (MVK) 和芳香醛之间不对称 Morita-Baylis-Hillman (MBH) 反应的有效助催化剂。相应的加合物以合理的化学产率和良好的对映选择性（高达 83% ee）形成。此外，与手性胺 4 和 L-脯氨酸的两种对映异构体的平行共催化反应表明，脯氨酸立体化学决定了新形成的手性中心的构型。此外，胺4a中游离羟基的存在提高了反应的对映选择性。基于这些发现，已经提出了这种助催化 MBH 反应的合理机制。
• 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。
• 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.
• Vedejs, Edwin; Lee, Namkyu, Journal of the American Chemical Society, 1995, vol. 117, # 3, p. 891 - 899
  作者：Vedejs, Edwin、Lee, Namkyu

  DOI：——

  日期：——