N'-(2-fluorobenzoyl)naphthalene-2-sulfonohydrazide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N'-(2-fluorobenzoyl)naphthalene-2-sulfonohydrazide
• 英文别名: CTx-0124143；2-fluoro-N'-naphthalen-2-ylsulfonylbenzohydrazide
• 化学式: C₁₇H₁₃FN₂O₃S
• 分子量: 344.366
• InChiKey: CMGWGSMHPCWLOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-萘磺酰氯 在 N-羟基-7-氮杂苯并三氮唑 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 20.0h， 生成 N'-(2-fluorobenzoyl)naphthalene-2-sulfonohydrazide
  参考文献：
  名称：

  Discovery of Benzoylsulfonohydrazides as Potent Inhibitors of the Histone Acetyltransferase KAT6A

  摘要：

  A high-throughput screen for inhibitors of the histone acetyltransferase, KAT6A, led to identification of an aryl sulfonohydrazide derivative (CTX-0124143) that inhibited KAT6A with an IC50 of 1.0 HM. Elaboration of the structure-activity relationship and medicinal chemistry optimization led to the discovery of WM-8014 (97), a highly potent inhibitor of KAT6A (IC50 = 0.008 /mu M). WM-8014 competes with acetyl-CoA (Ac-CoA), and X-ray crystallographic analysis demonstrated binding to the Ac-CoA binding site. Through inhibition of KAT6A activity, WM-8014 induces cellular senescence and represents a unique pharmacological tool,

  DOI：

  10.1021/acs.jmedchem.9b00665

文献信息

• [EN] COMPOUNDS CONTAINING A SULFONIC GROUP AS KAT INHIBITORS<br/>[FR] COMPOSÉS CONTENANT UN GROUPE SULFONIQUE EN TANT QU'INHIBITEURS DE KAT
  申请人：EPIZYME INC

  公开号：WO2018102419A1

  公开（公告）日：2018-06-07

  The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

  本发明提供了化合物、其药用可接受的组合物以及使用相同的方法。
• Discovery of Benzoylsulfonohydrazides as Potent Inhibitors of the Histone Acetyltransferase KAT6A
  作者：David J. Leaver、Benjamin Cleary、Nghi Nguyen、Daniel L. Priebbenow、H. Rachel Lagiakos、Julie Sanchez、Lian Xue、Fei Huang、Yuxin Sun、Prashant Mujumdar、Ramesh Mudududdla、Swapna Varghese、Silvia Teguh、Susan A. Charman、Karen L. White、Kasiram Katneni、Matthew Cuellar、Jessica M. Strasser、Jayme L. Dahlin、Michael A. Walters、Ian P. Street、Brendon J. Monahan、Kate E. Jarman、Helene Jousset Sabroux、Hendrik Falk、Matthew C. Chung、Stefan J. Hermans、Michael W. Parker、Tim Thomas、Jonathan B. Baell

  DOI：10.1021/acs.jmedchem.9b00665

  日期：2019.8.8

  A high-throughput screen for inhibitors of the histone acetyltransferase, KAT6A, led to identification of an aryl sulfonohydrazide derivative (CTX-0124143) that inhibited KAT6A with an IC50 of 1.0 HM. Elaboration of the structure-activity relationship and medicinal chemistry optimization led to the discovery of WM-8014 (97), a highly potent inhibitor of KAT6A (IC50 = 0.008 /mu M). WM-8014 competes with acetyl-CoA (Ac-CoA), and X-ray crystallographic analysis demonstrated binding to the Ac-CoA binding site. Through inhibition of KAT6A activity, WM-8014 induces cellular senescence and represents a unique pharmacological tool,