benzyl 2-((3S,4R)-2-oxo-3-((S)-2-oxo-4-phenyloxazolidin-3-yl)-4-((E)-styryl)azetidin-1-yl)acetate | 195309-03-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: benzyl 2-((3S,4R)-2-oxo-3-((S)-2-oxo-4-phenyloxazolidin-3-yl)-4-((E)-styryl)azetidin-1-yl)acetate
• 英文别名: benzyl 2-[(3S,4R)-2-oxo-3-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]-4-[(E)-2-phenylethenyl]azetidin-1-yl]acetate
• CAS: 195309-03-6
• 化学式: C₂₉H₂₆N₂O₅
• 分子量: 482.536
• InChiKey: SARCAGJNWLKRTO-KMUTWGJZSA-N

物化性质

• 沸点：
  740.5±60.0 °C(Predicted)
• 密度：
  1.340±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 2-((3S,4R)-2-oxo-3-((S)-2-oxo-4-phenyloxazolidin-3-yl)-4-((E)-styryl)azetidin-1-yl)acetate 、 三甲基乙酰氯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 以90%的产率得到benzyl 4,4-dimethyl-3-oxo-2-((3S,4R)-2-oxo-3-((S)-2-oxo-4-phenyloxazolidin-3-yl)-4-((E)-styryl)azetidin-1-yl)pentanoate
  参考文献：
  名称：

  Azetidinones as vasopressin V1a antagonists

  摘要：

  The azetidinone LY307174 (1) was identified as a screening lead for the vasopressin V1a receptor (IC50 45 nM at the human V1a receptor) based on molecular similarity to ketoconazole (2), a known antagonist of the luteinizing hormone releasing hormone receptor. Structure-activity relationships for the series were explored to optimize receptor affinity and pharmacokinetic properties, resulting in compounds with K-i values < 1 nM and brain levels after oral dosing similar to 100-fold higher than receptor affinities.[GRAPHICS](c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.031
• 作为产物：
  描述：

  (S)-(+)-2-氧代-4-苯基-3-恶唑烷乙酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 生成 benzyl 2-((3S,4R)-2-oxo-3-((S)-2-oxo-4-phenyloxazolidin-3-yl)-4-((E)-styryl)azetidin-1-yl)acetate
  参考文献：
  名称：

  Azetidinones as vasopressin V1a antagonists

  摘要：

  The azetidinone LY307174 (1) was identified as a screening lead for the vasopressin V1a receptor (IC50 45 nM at the human V1a receptor) based on molecular similarity to ketoconazole (2), a known antagonist of the luteinizing hormone releasing hormone receptor. Structure-activity relationships for the series were explored to optimize receptor affinity and pharmacokinetic properties, resulting in compounds with K-i values < 1 nM and brain levels after oral dosing similar to 100-fold higher than receptor affinities.[GRAPHICS](c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.031

文献信息

• EP0939632A4
  申请人：——

  公开号：EP0939632A4

  公开（公告）日：2002-09-25
• NON-PEPTIDYL VASOPRESSIN V1a ANTAGONISTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP0939632A1

  公开（公告）日：1999-09-08
• [EN] NON-PEPTIDYL VASOPRESSIN V1a ANTAGONISTS<br/>[FR] ANTAGONISTES DU RECEPTEUR DE LA VASOPRESSINE V1a NON PEPTIDYLIQUES
  申请人：ELI LILLY AND COMPANY

  公开号：WO1997030707A1

  公开（公告）日：1997-08-28

  (EN) This invention provides methods and 2-(azetidin-2-on-1-yl)acetic acid derivatives for the antagonism of the vasopressin V1a receptor.(FR) L'invention concerne des procédés et des dérivés de l'acide 2-(azétidin-2-on-1-yl)acétique agissant comme antagonistes du récepteur Vla de la vasopressine.
• Azetidinones as vasopressin V1a antagonists
  作者：Christophe D. Guillon、Gary A. Koppel、Michael J. Brownstein、Michael O. Chaney、Craig F. Ferris、Shi-fang Lu、Karine M. Fabio、Marvin J. Miller、Ned D. Heindel、David C. Hunden、Robin D.G. Cooper、Stephen W. Kaldor、Jeffrey J. Skelton、Bruce A. Dressman、Michael P. Clay、Mitchell I. Steinberg、Robert F. Bruns、Neal G. Simon

  DOI：10.1016/j.bmc.2006.12.031

  日期：2007.3

  The azetidinone LY307174 (1) was identified as a screening lead for the vasopressin V1a receptor (IC50 45 nM at the human V1a receptor) based on molecular similarity to ketoconazole (2), a known antagonist of the luteinizing hormone releasing hormone receptor. Structure-activity relationships for the series were explored to optimize receptor affinity and pharmacokinetic properties, resulting in compounds with K-i values < 1 nM and brain levels after oral dosing similar to 100-fold higher than receptor affinities.[GRAPHICS](c) 2006 Elsevier Ltd. All rights reserved.