2-(3-Chloro-benzyl)-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid | 927883-91-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(3-Chloro-benzyl)-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid
• 英文别名: 2-(3-chloro-benzyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-carboxylic acid；2-[(3-chlorophenyl)methyl]-1,3-dioxoisoindole-5-carboxylic acid
• CAS: 927883-91-8
• 化学式: C₁₆H₁₀ClNO₄
• 分子量: 315.713
• InChiKey: KNSDUDFZXGYLQA-UHFFFAOYSA-N

物化性质

• 沸点：
  543.7±40.0 °C(Predicted)
• 密度：
  1.537±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-Chloro-benzyl)-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-(3-chlorobenzyl)-N-(3-(2-methylpiperidin-1-yl)propyl)-1,3-dioxoisoindoline-5-carboxamide hydrochloride
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of 1,3-dioxoisoindoline-5-carboxamide derivatives as T-type calcium channel blockers

  摘要：

  A small molecule library of 1,3-dioxoisoindoline-5-carboxamides 4 was designed based on the pharmacophore model, synthesized and biologically evaluated as potential T-type calcium channel blockers. The most active compounds 4d and 4n show T-type calcium channel blocking activity with IC50 values of 0.93 and 0.96 mu M, respectively. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.042
• 作为产物：
  描述：

  3-氯苄胺 、 偏苯三酸酐 在 溶剂黄146 作用下， 生成 2-(3-Chloro-benzyl)-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid
  参考文献：
  名称：

  吡唑-异吲哚啉-1,3-二酮杂化物：4-羟基苯丙酮酸双加氧酶抑制剂的有前途的支架

  摘要：

  4-羟基苯基丙酮酸双加氧酶（HPPD，EC 1.13.11.27）抑制剂的发现由于其作为除草剂除草剂的巨大潜力而​​成为一个活跃的研究领域。从已知的HPPD抑制剂的结合模式出发，通过将2-苯并lethen-1-ol和isoindoline-1,3-dione片段杂交，设计并合成了一系列具有新分子支架的HPPD抑制剂。的体外试验的结果表明，新合成的化合物显示出良好的HPPD抑制活性IC 50个针对重组值拟南芥HPPD（在HPPD）范围为0.0039μM到超过1微米。最有希望的是化合物4ae，2-苄基-5-（5-羟基-1,3-二甲基-1 H吡唑-4-羰基）异二氢吲哚-1,3-二酮，显示出最高的在与HPPD抑制活性ķ我3.92纳米的值，使得它大约10倍，比磺酰草吡唑更有效（ķ我= 44 nM）的和稍微更比甲基磺草酮有效（K i = 4.56 nM）。此外，At HPPD– 4ae的共晶体结构该复合物已成功解析为1

  DOI：

  10.1021/acs.jafc.9b04917

文献信息

• Pyrazole–Isoindoline-1,3-dione Hybrid: A Promising Scaffold for 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors
  作者：Bo He、Jin Dong、Hong-Yan Lin、Meng-Yao Wang、Xian-Kai Li、Bai-Feng Zheng、Qiong Chen、Ge-Fei Hao、Wen-Chao Yang、Guang-Fu Yang

  DOI：10.1021/acs.jafc.9b04917

  日期：2019.10.2

  The discovery of 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) inhibitors has been an active area of research due to their great potential as herbicides for weed control. Starting from the binding mode of known inhibitors of HPPD, a series of HPPD inhibitors with new molecular scaffolds were designed and synthesized by hybridizing 2-benzoylethen-1-ol and isoindoline-1,3-dione fragments. The

  4-羟基苯基丙酮酸双加氧酶（HPPD，EC 1.13.11.27）抑制剂的发现由于其作为除草剂除草剂的巨大潜力而​​成为一个活跃的研究领域。从已知的HPPD抑制剂的结合模式出发，通过将2-苯并lethen-1-ol和isoindoline-1,3-dione片段杂交，设计并合成了一系列具有新分子支架的HPPD抑制剂。的体外试验的结果表明，新合成的化合物显示出良好的HPPD抑制活性IC 50个针对重组值拟南芥HPPD（在HPPD）范围为0.0039μM到超过1微米。最有希望的是化合物4ae，2-苄基-5-（5-羟基-1,3-二甲基-1 H吡唑-4-羰基）异二氢吲哚-1,3-二酮，显示出最高的在与HPPD抑制活性ķ我3.92纳米的值，使得它大约10倍，比磺酰草吡唑更有效（ķ我= 44 nM）的和稍微更比甲基磺草酮有效（K i = 4.56 nM）。此外，At HPPD– 4ae的共晶体结构该复合物已成功解析为1
• 1,3-DIOXOISOINDOLE DERIVATIVES HAVING SELECTIVE ANTAGONISM OF T-TYPE CALCIUM CHANNEL
  申请人：Cho Yong Seo

  公开号：US20070259867A1

  公开（公告）日：2007-11-08

  The present invention relates to 1,3-dioxoisoindole derivatives of Formula (1) or pharmaceutically acceptable salts thereof, a preparation method thereof and use thereof as a T-type calcium channel antagonist, based on the fact that 1,3-dioxoisoindole derivatives of Formula (1) show selective antagonistic activity against T-type calcium channel, thus being effective in treating brain diseases, cardiac diseases and neurogenic pains: wherein R 1 is a phenyl or a benzyl group, optionally substituted with a moiety selected from the group consisting of a halogen atom, a C 1 -C 6 alkoxy, a C 1 -C 6 alkyl, and a cyano group; R 2 is a heterocyclic group selected from the group consisting of piperidinyl, pyrrolidinyl, morpholinyl, and piperazinyl groups, wherein the heterocyclic group is optionally substituted with a C 1 -C 6 alkyl group; and n is 1 or 2.

  本发明涉及公式（1）的1,3-二氧杂异吲哚衍生物或其药学上可接受的盐，其制备方法和用作T型钙通道拮抗剂的用途，基于公式（1）的1,3-二氧杂异吲哚衍生物显示出选择性拮抗T型钙通道的活性，因此对治疗脑部疾病，心脏疾病和神经痛有效。其中，R1是苯基或苄基，可选地被取代为来自卤素原子，C1-C6烷氧基，C1-C6烷基和氰基的基团中选出的一个基团；R2是选自哌啶基，吡咯烷基，吗啉基和哌嗪基的杂环基团，其中该杂环基团可选地被C1-C6烷基取代；n为1或2。
• 1,3-dioxoisoindole derivatives having selective antagonism of T-type calcium channel
  申请人：Korea Institute of Science and Technology

  公开号：US07319098B2

  公开（公告）日：2008-01-15

  The present invention relates to 1,3-dioxoisoindole derivatives of Formula (1) or pharmaceutically acceptable salts thereof, a preparation method thereof and use thereof as a T-type calcium channel antagonist, based on the fact that 1,3-dioxoisoindole derivatives of Formula (1) show selective antagonistic activity against T-type calcium channel, thus being effective in treating brain diseases, cardiac diseases and neurogenic pains: wherein R1 is a phenyl or a benzyl group, optionally substituted with a moiety selected from the group consisting of a halogen atom, a C1-C6 alkoxy, a C1-C6 alkyl, and a cyano group; R2 is a heterocyclic group selected from the group consisting of piperidinyl, pyrrolidinyl, morpholinyl, and piperazinyl groups, wherein the heterocyclic group is optionally substituted with a C1-C6 alkyl group; and n is 1 or 2.

  本发明涉及公式（1）的1,3-二氧代异吲哚衍生物或其药学上可接受的盐，其制备方法和用作T型钙通道拮抗剂的用途。基于1,3-二氧代异吲哚衍生物具有对T型钙通道的选择性拮抗活性的事实，因此在治疗脑部疾病、心脏疾病和神经性疼痛方面具有有效性。其中，R1为苯基或苄基，可选地被取代为来自卤素原子、C1-C6烷氧基、C1-C6烷基和氰基的基团中的一种；R2为从哌啶基、吡咯烷基、吗啉基和哌嗪基中选择的杂环基团，其中杂环基团可选地被取代为C1-C6烷基；n为1或2。
• US7319098B2
  申请人：——

  公开号：US7319098B2

  公开（公告）日：2008-01-15
• Design, synthesis, and biological evaluation of 1,3-dioxoisoindoline-5-carboxamide derivatives as T-type calcium channel blockers
  作者：Hwa Sil Kim、Yoonjee Kim、Munikumar Reddy Doddareddy、Seon Hee Seo、Hyewhon Rhim、Jinsung Tae、Ae Nim Pae、Hyunah Choo、Yong Seo Cho

  DOI：10.1016/j.bmcl.2006.10.042

  日期：2007.1

  A small molecule library of 1,3-dioxoisoindoline-5-carboxamides 4 was designed based on the pharmacophore model, synthesized and biologically evaluated as potential T-type calcium channel blockers. The most active compounds 4d and 4n show T-type calcium channel blocking activity with IC50 values of 0.93 and 0.96 mu M, respectively. (c) 2006 Elsevier Ltd. All rights reserved.