4-(4-Methylnaphthalen-1-yl)-2-[[4-(3-morpholin-4-ylpropoxy)phenyl]sulfonylamino]benzoic acid | 1580484-08-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-(4-Methylnaphthalen-1-yl)-2-[[4-(3-morpholin-4-ylpropoxy)phenyl]sulfonylamino]benzoic acid
• 英文别名: 4-(4-methylnaphthalen-1-yl)-2-[[4-(3-morpholin-4-ylpropoxy)phenyl]sulfonylamino]benzoic acid
• CAS: 1580484-08-7
• 化学式: C₃₁H₃₂N₂O₆S
• 分子量: 560.671
• InChiKey: DMAMRXTYIWXNNC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 4-(4-Methylnaphthalen-1-yl)-2-[[4-(3-morpholin-4-ylpropoxy)phenyl]sulfonylamino]benzoic acid
  参考文献：
  名称：

  Fragment-based discovery of potent inhibitors of the anti-apoptotic MCL-1 protein

  摘要：

  Apoptosis is regulated by the BCL-2 family of proteins, which is comprised of both pro-death and pro-survival members. Evasion of apoptosis is a hallmark of malignant cells. One way in which cancer cells achieve this evasion is thru overexpression of the pro-survival members of the BCL-2 family. Overexpression of MCL-1, a pro-survival protein, has been shown to be a resistance factor for Navitoclax, a potent inhibitor of BCL-2 and BCL-XL. Here we describe the use of fragment screening methods and structural biology to drive the discovery of novel MCL-1 inhibitors from two distinct structural classes. Specifically, cores derived from a biphenyl sulfonamide and salicylic acid were uncovered in an NMR-based fragment screen and elaborated using high throughput analog synthesis. This culminated in the discovery of selective and potent inhibitors of MCL-1 that may serve as promising leads for medicinal chemistry optimization efforts.

  DOI：

  10.1016/j.bmcl.2014.02.010

文献信息

• Fragment-based discovery of potent inhibitors of the anti-apoptotic MCL-1 protein
  作者：Andrew M. Petros、Steven L. Swann、Danying Song、Kerren Swinger、Chang Park、Haichao Zhang、Michael D. Wendt、Aaron R. Kunzer、Andrew J. Souers、Chaohong Sun

  DOI：10.1016/j.bmcl.2014.02.010

  日期：2014.3

  Apoptosis is regulated by the BCL-2 family of proteins, which is comprised of both pro-death and pro-survival members. Evasion of apoptosis is a hallmark of malignant cells. One way in which cancer cells achieve this evasion is thru overexpression of the pro-survival members of the BCL-2 family. Overexpression of MCL-1, a pro-survival protein, has been shown to be a resistance factor for Navitoclax, a potent inhibitor of BCL-2 and BCL-XL. Here we describe the use of fragment screening methods and structural biology to drive the discovery of novel MCL-1 inhibitors from two distinct structural classes. Specifically, cores derived from a biphenyl sulfonamide and salicylic acid were uncovered in an NMR-based fragment screen and elaborated using high throughput analog synthesis. This culminated in the discovery of selective and potent inhibitors of MCL-1 that may serve as promising leads for medicinal chemistry optimization efforts.