4-chloro-2-[(1,3-dioxo-1,3-dihydroisobenzofuran-5-carbonyl)amino]benzoic acid | 1235866-67-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-chloro-2-[(1,3-dioxo-1,3-dihydroisobenzofuran-5-carbonyl)amino]benzoic acid
• 英文别名: 4-Chloro-2-[(1,3-dioxo-2-benzofuran-5-carbonyl)amino]benzoic acid
• CAS: 1235866-67-7
• 化学式: C₁₆H₈ClNO₆
• 分子量: 345.696
• InChiKey: HRPDRMJTJHDJHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-chloro-2-[(1,3-dioxo-1,3-dihydroisobenzofuran-5-carbonyl)amino]benzoic acid 、 3-氨基苯酚 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 18.0h， 以84%的产率得到4-chloro-2-([2-(3-hydroxyphenyl)-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carbonyl]amino)benzoic acid
  参考文献：
  名称：

  The Pthaladyns: GTP Competitive Inhibitors of Dynamin I and II GTPase Derived from Virtual Screening

  摘要：

  We report the development of a homology model for the GTP binding domain of human dynamin I based on the corresponding crystal structure of Dictyostelium discoidum dynamin A. Virtual screening identified 2-[(2-biphenyl-2-yl-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carbonyl)amino]-4-chlorobenzoic acid (1) as a similar to 170 mu M potent inhibitor. Homology modeling- and focused library-led synthesis resulted in development of a series of active compounds (the "pthaladyns") with 4-chloro-2-(2-(4-(hydroxymethyl)phenyl)-1,3-dioxoisoindoline-5-carboxamido)benzoic acid (29), a 4.58 +/- 0.06 mu M dynamin I GTPase inhibitor. Pthaladyn-29 displays borderline selectivity for dynamin I relative to dynamin IT (similar to 5-10 fold). Only pthaladyn-23 (dynamin I IC50 17.4 +/- 5.8 mu M)was an effective inhibitor of dynamin I mediated synaptic vesicle endocytosis in brain synaptosomes with an IC50 of 12.9 +/- 5.9 mu M. This compound was also competitive with respect to Mg2+. GTP. Thus the pthaladyns are the first GTP competitive inhibitors of dynamin I and II GTPase and may be effective new tools for the study of neuronal endocytosis.

  DOI：

  10.1021/jm100442u
• 作为产物：
  描述：

  氯化偏苯三酸酐 、 2-氨基-4-氯苯甲酸 以 四氢呋喃 为溶剂， 以76%的产率得到4-chloro-2-[(1,3-dioxo-1,3-dihydroisobenzofuran-5-carbonyl)amino]benzoic acid
  参考文献：
  名称：

  The Pthaladyns: GTP Competitive Inhibitors of Dynamin I and II GTPase Derived from Virtual Screening

  摘要：

  We report the development of a homology model for the GTP binding domain of human dynamin I based on the corresponding crystal structure of Dictyostelium discoidum dynamin A. Virtual screening identified 2-[(2-biphenyl-2-yl-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carbonyl)amino]-4-chlorobenzoic acid (1) as a similar to 170 mu M potent inhibitor. Homology modeling- and focused library-led synthesis resulted in development of a series of active compounds (the "pthaladyns") with 4-chloro-2-(2-(4-(hydroxymethyl)phenyl)-1,3-dioxoisoindoline-5-carboxamido)benzoic acid (29), a 4.58 +/- 0.06 mu M dynamin I GTPase inhibitor. Pthaladyn-29 displays borderline selectivity for dynamin I relative to dynamin IT (similar to 5-10 fold). Only pthaladyn-23 (dynamin I IC50 17.4 +/- 5.8 mu M)was an effective inhibitor of dynamin I mediated synaptic vesicle endocytosis in brain synaptosomes with an IC50 of 12.9 +/- 5.9 mu M. This compound was also competitive with respect to Mg2+. GTP. Thus the pthaladyns are the first GTP competitive inhibitors of dynamin I and II GTPase and may be effective new tools for the study of neuronal endocytosis.

  DOI：

  10.1021/jm100442u

文献信息

• The <i>Pthaladyns</i>: GTP Competitive Inhibitors of Dynamin I and II GTPase Derived from Virtual Screening
  作者：Luke R. Odell、Dian Howan、Christopher P. Gordon、Mark J. Robertson、Ngoc Chau、Anna Mariana、Ainslie E. Whiting、Ruben Abagyan、James A. Daniel、Nick N. Gorgani、Phillip J. Robinson、Adam McCluskey

  DOI：10.1021/jm100442u

  日期：2010.7.22

  We report the development of a homology model for the GTP binding domain of human dynamin I based on the corresponding crystal structure of Dictyostelium discoidum dynamin A. Virtual screening identified 2-[(2-biphenyl-2-yl-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carbonyl)amino]-4-chlorobenzoic acid (1) as a similar to 170 mu M potent inhibitor. Homology modeling- and focused library-led synthesis resulted in development of a series of active compounds (the "pthaladyns") with 4-chloro-2-(2-(4-(hydroxymethyl)phenyl)-1,3-dioxoisoindoline-5-carboxamido)benzoic acid (29), a 4.58 +/- 0.06 mu M dynamin I GTPase inhibitor. Pthaladyn-29 displays borderline selectivity for dynamin I relative to dynamin IT (similar to 5-10 fold). Only pthaladyn-23 (dynamin I IC50 17.4 +/- 5.8 mu M)was an effective inhibitor of dynamin I mediated synaptic vesicle endocytosis in brain synaptosomes with an IC50 of 12.9 +/- 5.9 mu M. This compound was also competitive with respect to Mg2+. GTP. Thus the pthaladyns are the first GTP competitive inhibitors of dynamin I and II GTPase and may be effective new tools for the study of neuronal endocytosis.