(2R,4S)-4-hydroxy-1-(2-nitrophenyl)proline | 214143-76-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,4S)-4-hydroxy-1-(2-nitrophenyl)proline
• 英文别名: (2R,4S)-4-Hydroxy-1-(2-Nitrophenyl) Proline；(2R,4S)-4-hydroxy-1-(2-nitrophenyl)pyrrolidine-2-carboxylic acid
• CAS: 214143-76-7
• 化学式: C₁₁H₁₂N₂O₅
• 分子量: 252.227
• InChiKey: ZCNVMFKSWODSRV-OIBJUYFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,4S)-4-hydroxy-1-(2-nitrophenyl)proline 在 palladium on activated charcoal sodium tetrahydroborate 、 氢气 、 三乙胺 作用下， 生成 (2S,3aR)-2-hydroxy-1,2,3,3a,4,5-hexahydro-pyrrolo<1,2-a>quinoxaline hydrochloride
  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：

  (4R)-4-羟基-D-脯氨酸甲酯盐酸盐 在 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 溶剂黄146 、 三乙胺 、 三苯基膦 作用下， 以 乙腈 为溶剂， 反应 38.0h， 生成 (2R,4S)-4-hydroxy-1-(2-nitrophenyl)proline
  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 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。
• US6225306B1
  申请人：——

  公开号：US6225306B1

  公开（公告）日：2001-05-01
• 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.