[[3-(2-amino-2-oxoethyl)-1-[(3-chlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid ethyl ester | 164083-93-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [[3-(2-amino-2-oxoethyl)-1-[(3-chlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid ethyl ester
• 英文别名: ethyl 2-[3-(2-amino-2-oxoethyl)-1-[(3-chlorophenyl)methyl]-2-methylindol-4-yl]oxyacetate
• CAS: 164083-93-6
• 化学式: C₂₂H₂₃ClN₂O₄
• 分子量: 414.889
• InChiKey: PHYHTMTXWDTOBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [[3-(2-amino-2-oxoethyl)-1-[(3-chlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以88%的产率得到[[3-(2-amino-2-oxoethyl)-1-[(3-chlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid sodium salt
  参考文献：
  名称：

  Indole Inhibitors of Human Nonpancreatic Secretory Phospholipase A₂. 2. Indole-3-acetamides with Additional Functionality

  摘要：

  As reported in our previous paper, a series of indole-3-acetamides which possessed potency and selectivity as inhibitors of human nonpancreatic secretory phospholipase A(2)(hnps-PLA(2)) was developed. The design of these compounds was based on information derived from x-ray crystal structures determined for complexes between the enzyme and its inhibitors. We describe here the further implementation of this structure-based design strategy and continued SAR development to produce indole-3-acetamides with additional functionalities which provide increased interaction with important residues within the enzyme active site. These efforts led to inhibitors with substantially enhanced potency and selectivity.

  DOI：

  10.1021/jm960486n
• 作为产物：
  描述：

  2-[1-(3-Chloro-benzyl)-4-methoxy-2-methyl-1H-indol-3-yl]-acetamide 在 三溴化硼 、 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 反应 4.25h， 生成 [[3-(2-amino-2-oxoethyl)-1-[(3-chlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid ethyl ester
  参考文献：
  名称：

  Indole Inhibitors of Human Nonpancreatic Secretory Phospholipase A₂. 2. Indole-3-acetamides with Additional Functionality

  摘要：

  As reported in our previous paper, a series of indole-3-acetamides which possessed potency and selectivity as inhibitors of human nonpancreatic secretory phospholipase A(2)(hnps-PLA(2)) was developed. The design of these compounds was based on information derived from x-ray crystal structures determined for complexes between the enzyme and its inhibitors. We describe here the further implementation of this structure-based design strategy and continued SAR development to produce indole-3-acetamides with additional functionalities which provide increased interaction with important residues within the enzyme active site. These efforts led to inhibitors with substantially enhanced potency and selectivity.

  DOI：

  10.1021/jm960486n

文献信息

• 1H-indole-3-acetamide sPLA.sub.2 inhibitors
  申请人：Eli Lilly and Company

  公开号：US05684034A1

  公开（公告）日：1997-11-04

  A class of novel 1-indole-3-acetamides represented by the formula; ##STR1## is disclosed together with the use of such indole compounds for inhibiting sPLA.sub.2 mediated release of fatty acids.

  一类由以下式表示的新型1-吲哚-3-乙酰胺类化合物被揭示，同时还公开了利用这类吲哚化合物抑制sPLA.sub.2介导的脂肪酸释放的用途。
• 1H-indole-3-acetamide derivatives as sPLA2 inhibitors
  申请人：ELI LILLY AND COMPANY

  公开号：EP0620215B1

  公开（公告）日：1999-08-18
• US5684034A
  申请人：——

  公开号：US5684034A

  公开（公告）日：1997-11-04
• US6252084B1
  申请人：——

  公开号：US6252084B1

  公开（公告）日：2001-06-26
• Indole Inhibitors of Human Nonpancreatic Secretory Phospholipase A₂. 2. Indole-3-acetamides with Additional Functionality
  作者：Robert D. Dillard、Nicholas J. Bach、Susan E. Draheim、Dennis R. Berry、Donald G. Carlson、Nickolay Y. Chirgadze、David K. Clawson、Lawrence W. Hartley、Lea M. Johnson、Noel D. Jones、Emma R. McKinney、Edward D. Mihelich、Jennifer L. Olkowski、Richard W. Schevitz、Amy C. Smith、David W. Snyder、Cynthia D. Sommers、Jean-Pierre Wery

  DOI：10.1021/jm960486n

  日期：1996.1.1

  As reported in our previous paper, a series of indole-3-acetamides which possessed potency and selectivity as inhibitors of human nonpancreatic secretory phospholipase A(2)(hnps-PLA(2)) was developed. The design of these compounds was based on information derived from x-ray crystal structures determined for complexes between the enzyme and its inhibitors. We describe here the further implementation of this structure-based design strategy and continued SAR development to produce indole-3-acetamides with additional functionalities which provide increased interaction with important residues within the enzyme active site. These efforts led to inhibitors with substantially enhanced potency and selectivity.