3-(1-Benzyl-5-methoxy-2-methyl-1H-indol-3-yl)-propionamide | 185063-67-6

• 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: 3-(1-Benzyl-5-methoxy-2-methyl-1H-indol-3-yl)-propionamide
• 英文别名: 3-(1-benzyl-5-methoxy-2-methylindol-3-yl)propanamide
• CAS: 185063-67-6
• 化学式: C₂₀H₂₂N₂O₂
• 分子量: 322.407
• InChiKey: NPTBHXHZOWLPMJ-UHFFFAOYSA-N

物化性质

• 熔点：
  151-153 °C
• 沸点：
  595.4±50.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(1-Benzyl-5-methoxy-2-methyl-1H-indol-3-yl)-propionamide 在 三溴化硼 、 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 反应 5.5h， 生成 4-[1-Benzyl-3-(2-carbamoyl-ethyl)-2-methyl-1H-indol-5-yloxy]-butyric 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
• 作为产物：
  描述：

  4-甲氧基苯肼盐酸盐 在 盐酸 、 Raney nickel (W-4) 、 potassium tert-butylate 、 肼 作用下， 以 乙醇 为溶剂， 反应 65.0h， 生成 3-(1-Benzyl-5-methoxy-2-methyl-1H-indol-3-yl)-propionamide
  参考文献：
  名称：

  人非胰腺分泌型磷脂酶A2的吲哚抑制剂。1.吲哚-3-乙酰胺。

  摘要：

  磷脂酶（PLA）在涉及炎症过程的各种类型生物活性脂质的生物合成中产生限速前体。在几种病理条件下已检测到人类非胰腺分泌型磷脂酶A2（hnps-PLA2）水平升高。该酶的抑制剂可以具有治疗用途。进行了广泛的筛选程序以鉴定可能抑制hnps-PLA2的化学结构。通过筛选程序生成的先导化合物之一是5-甲氧基-2-甲基-1-（苯甲基）-1H-吲哚-3-乙酸（13a）。我们描述了一系列吲哚-3-乙酰胺及其衍生化合物的合成，结构-活性关系以及药理活性。

  DOI：

  10.1021/jm960485v

文献信息

• 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.
• Indole Inhibitors of Human Nonpancreatic Secretory Phospholipase A₂. 1. Indole-3-acetamides
  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/jm960485v

  日期：1996.1.1

  Phospholipases (PLAs) produce rate-limiting precursors in the biosynthesis of various types of biologically active lipids involved in inflammatory processes. Increased levels of human nonpancreatic secretory phospholipase A2 (hnps-PLA2) have been detected in several pathological conditions. An inhibitor of this enzyme could have therapeutic utility. A broad screening program was carried out to identify

  磷脂酶（PLA）在涉及炎症过程的各种类型生物活性脂质的生物合成中产生限速前体。在几种病理条件下已检测到人类非胰腺分泌型磷脂酶A2（hnps-PLA2）水平升高。该酶的抑制剂可以具有治疗用途。进行了广泛的筛选程序以鉴定可能抑制hnps-PLA2的化学结构。通过筛选程序生成的先导化合物之一是5-甲氧基-2-甲基-1-（苯甲基）-1H-吲哚-3-乙酸（13a）。我们描述了一系列吲哚-3-乙酰胺及其衍生化合物的合成，结构-活性关系以及药理活性。