5-hydroxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetic acid hydrazide | 163687-89-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-hydroxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetic acid hydrazide
• 英文别名: 2-(1-benzyl-5-hydroxy-2-methylindol-3-yl)acetohydrazide
• CAS: 163687-89-6
• 化学式: C₁₈H₁₉N₃O₂
• 分子量: 309.368
• InChiKey: UWCQKSFRTIYNMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  80.3
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-hydroxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetic acid hydrazide 在 sodium hydride 、 二甲基亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 19.67h， 生成
  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：

  5-methoxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetic acid hydrazide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以39%的产率得到5-hydroxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetic acid hydrazide
  参考文献：
  名称：

  1H-indole-3-acetic acid hydrazide sPLA.sub.2 inhibitors

  摘要：

  一类新型的1H-吲哚-3-乙酸肼类化合物被揭示，以及利用这类吲哚化合物抑制sPLA.sub.2介导的脂肪酸（例如花生四烯酸）释放，用于治疗诸如感染性休克等疾病。

  公开号：

  US05578634A1

文献信息

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

  公开号：US05578634A1

  公开（公告）日：1996-11-26

  A class of novel 1H-indole-3-acetic acid hydrazides is disclosed together with the use of such indole compounds for inhibiting sPLA.sub.2 mediated release of fatty acids (e.g., arachidonic acid) for treatment of conditions such as septic shock.

  一类新型的1H-吲哚-3-乙酸肼类化合物被揭示，以及利用这类吲哚化合物抑制sPLA.sub.2介导的脂肪酸（例如花生四烯酸）释放，用于治疗诸如感染性休克等疾病。
• 1H-indole-3-acetic acid hydrazide sPLA2 inhibitors
  申请人：ELI LILLY AND COMPANY

  公开号：EP0620214B1

  公开（公告）日：1999-03-03
• US5578634A
  申请人：——

  公开号：US5578634A

  公开（公告）日：1996-11-26
• 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.