(4S,11E)-18-chloro-2-oxo-14-oxa-3,6,7,8-tetrazatricyclo[13.3.1.16,9]icosa-1(18),7,9(20),11,15(19),16-hexaene-4-carboxylic acid | 1534386-83-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (4S,11E)-18-chloro-2-oxo-14-oxa-3,6,7,8-tetrazatricyclo[13.3.1.16,9]icosa-1(18),7,9(20),11,15(19),16-hexaene-4-carboxylic acid
• CAS: 1534386-83-8
• 化学式: C₁₆H₁₅ClN₄O₄
• 分子量: 362.772
• InChiKey: PIRIIWBJGLBSQS-YUKKFKLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氯-5-羟基苯甲酸 在 Hoveyda-Grubbs catalyst second generation 、 1-羟基苯并三唑 、 四正丁基氢氧化膦 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.5h， 生成 (4S,11E)-18-chloro-2-oxo-14-oxa-3,6,7,8-tetrazatricyclo[13.3.1.16,9]icosa-1(18),7,9(20),11,15(19),16-hexaene-4-carboxylic acid 、 (14Z,3S,9Z)-66-chloro-5-oxo-11H-7-oxa-4-aza-1(1,4)-triazola-6(1,3)-benzenacycloundecaphan-9-ene-3-carboxylic acid
  参考文献：
  名称：

  Small Macrocycles As Highly Active Integrin α2β1 Antagonists

  摘要：

  Starting from clinical candidates Firategrast, Valategrast, and AJM-300, a series of novel macrocyclic platelet collagen receptor alpha 2 beta 1 antagonists were developed. The amino acid derived low molecular weight 14-18-membered macrocycles turned out to be highly active toward integrin alpha 2 beta 1 with IC(50)s in the low nanomolar range. The conformation of the macrocycles was found to be highly important for the activity, and an X-ray crystal structure was obtained to clarify this. Subsequent docking into the metal-ion-dependent adhesion site (MIDAS) of a beta 1 unit revealed a binding model indicating key binding features. Macrocycle 38 was selected for further in vitro and in vivo profiling.

  DOI：

  10.1021/ml4004556

文献信息

• Small Macrocycles As Highly Active Integrin α2β1 Antagonists
  作者：Nis Halland、Horst Blum、Christian Buning、Markus Kohlmann、Andreas Lindenschmidt

  DOI：10.1021/ml4004556

  日期：2014.2.13

  Starting from clinical candidates Firategrast, Valategrast, and AJM-300, a series of novel macrocyclic platelet collagen receptor alpha 2 beta 1 antagonists were developed. The amino acid derived low molecular weight 14-18-membered macrocycles turned out to be highly active toward integrin alpha 2 beta 1 with IC(50)s in the low nanomolar range. The conformation of the macrocycles was found to be highly important for the activity, and an X-ray crystal structure was obtained to clarify this. Subsequent docking into the metal-ion-dependent adhesion site (MIDAS) of a beta 1 unit revealed a binding model indicating key binding features. Macrocycle 38 was selected for further in vitro and in vivo profiling.