tert-butyl N-[4-(1,3-dioxoisoindol-2-yl)oxybutyl]carbamate | 1596368-96-5

• 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: tert-butyl N-[4-(1,3-dioxoisoindol-2-yl)oxybutyl]carbamate
• CAS: 1596368-96-5
• 化学式: C₁₇H₂₂N₂O₅
• 分子量: 334.372
• InChiKey: GDZLZKNZWAEXGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[4-(1,3-dioxoisoindol-2-yl)oxybutyl]carbamate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 肼 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 tert-butyl (4-((3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamido)oxy)butyl)carbamate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of RGD-Conjugated MEK1/2 Kinase Inhibitors for Integrin-Targeted Cancer Therapy

  摘要：

  两种源于MEK1/2激酶抑制剂PD0325901的新型RGD-MEKI偶联物系列已被开发用于整合素受体介导的癌症治疗。第一系列，烷氧基胺类似物RGD-MEKI偶联物9a-g通过与PD0325901相同的机制在黑色素瘤A375细胞中显示出抗增殖活性。PEGylation使9f在A375测定中的IC50值增加了三倍，而多cRGD肽负载则显著提高了9g在整合素高表达的U87细胞中的受体特异性抗增殖活性。在第二系列中，RGD-PD0325901 13相比烷氧基胺类似物，通过抑制ERK通路活性和癌细胞的DNA复制，显示出显著增强的抗肿瘤特性。此外，13在U87测定中比PD0325901显示出更强的抗增殖活性，且呈剂量依赖性。所有这些数据表明，带有酯键连接的RGD-MEKI偶联物提高了对整合素高表达肿瘤细胞的靶向能力，从而增强了抗癌疗效。

  DOI：

  10.3390/molecules181113957
• 作为产物：
  描述：

  4-(N-叔丁氧羰基氨基)-1-丁醇 在 咪唑 、 碘 、 sodium hydride 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 13.25h， 生成 tert-butyl N-[4-(1,3-dioxoisoindol-2-yl)oxybutyl]carbamate
  参考文献：
  名称：

  Synthesis of fluorescent molecular probes based on cis-cinnamic acid and molecular imaging of lettuce roots

  摘要：

  We synthesized azo dye- and fluorescence-labeled cis-cinnamic acid analogues possessing inhibitory activity agaihst lettuce root growth and a trans-isomer without bioactivity as a control probe. The radicles incubated with the azo dye-labeled analogue were stained red, with their tips especially deeply dyed. The fluorescent images of the radicles incubated with each of these molecular probes depicted that the root cap was fluorescence-stained. However, images of the control radicles prepared by staining with the trans-isomer fluorescent probe did not show emission at the root cap. These contrasts suggest specific localization of the cis-cinnamate analogue at the columella cells. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2016.08.060

文献信息

• ORNITHINE DECARBOXYLASE INHIBITING BRANCHED AMINOOXY AMINO ALKANE DERIVATIVES
  申请人：CIBA-GEIGY AG

  公开号：EP0644873B1

  公开（公告）日：1997-03-12
• US5610195A
  申请人：——

  公开号：US5610195A

  公开（公告）日：1997-03-11
• [EN] ORNITHINE DECARBOXYLASE INHIBITING BRANCHED AMINOOXY AMINO ALKANE DERIVATIVES<br/>[FR] DERIVES D'ALCANE AMINO AMINOOXY A CHAINE RAMIFIEE INHIBITEURS DE LA DECARBOXYLASE D'ORNITHINE
  申请人：CIBA-GEIGY AG

  公开号：WO1994024094A1

  公开（公告）日：1994-10-27

  (EN) Compounds of formula (I) in which (a) four of the radicals R1, R2, R3, R4, R5 and R6 are hydrogen and the others independently of one another are in each case C1-C2alkyl, these groups being bonded to the same carbon atom or to two different carbon atoms, or (b) five of the radicals R1, R2, R3, R4, R5 and R6 are hydrogen and the other radical is C1-C2alkyl or hydroxymethyl, or salts thereof, are described. The compounds of formula (I) and their salts are ornithine decarboxylase inhibitors.(FR) L'invention concerne des composés selon la formule (I) dans laquelle (a) quatre des radicaux suivants, R1, R2, R3, R4, R5 et R6, représentent l'hydrogène et les autres, indépendamment l'un de l'autre représentent dans chaque cas un alkyle C1-C2, ces groupes étant reliés au même atome de carbone ou à deux atomes de carbone différents, ou (b) cinq des radicaux suivants: R1, R2, R3, R4, R5 et R6 représentent l'hydrogène et le radical restant représente un alkyle C1-C2 ou un hydroxyméthyle, ainsi que leurs sels. Les composés selon la formule (I) et leurs sels sont des inhibiteurs de la décarboxylase d'ornithine.
• Synthesis and Biological Evaluation of RGD-Conjugated MEK1/2 Kinase Inhibitors for Integrin-Targeted Cancer Therapy
  作者：Xiaoxiao Li、Jianjun Hou、Chao Wang、Xinjie Liu、Hongyan He、Ping Xu、Zhenjun Yang、Zili Chen、Yun Wu、Lihe Zhang

  DOI：10.3390/molecules181113957

  日期：——

  Two novel series of RGD-MEKI conjugates derived from a MEK1/2 kinase inhibitor—PD0325901—have been developed for integrin receptor mediated anticancer therapy. The first series, alkoxylamine analog RGD-MEKI conjugates 9a–g showed anti-proliferation activity in melanoma A375 cells by the same mechanism as that of PD0325901. PEGylation increased the IC50 value of 9f three-fold in the A375 assay, and the multi-cRGD peptide cargo significantly improved the receptor specific anti-proliferation activity of 9g in integrin-overexpressing U87 cells. In the second series, RGD-PD0325901 13 exhibited significantly increased antitumor properties compared to the alkoxylamine analogs by both inhibition of the ERK pathway activity and DNA replication of the cancer cells. Furthermore, 13 displayed more potent anti-proliferation activity in the U87 assay than PD0325901 in a dose-dependent manner. All these data demonstrate that RGD-MEKI conjugates with an ester bond linkage enhanced anticancer efficacy with improved targeting capability toward integrin-overexpressing tumor cells.

  两种源于MEK1/2激酶抑制剂PD0325901的新型RGD-MEKI偶联物系列已被开发用于整合素受体介导的癌症治疗。第一系列，烷氧基胺类似物RGD-MEKI偶联物9a-g通过与PD0325901相同的机制在黑色素瘤A375细胞中显示出抗增殖活性。PEGylation使9f在A375测定中的IC50值增加了三倍，而多cRGD肽负载则显著提高了9g在整合素高表达的U87细胞中的受体特异性抗增殖活性。在第二系列中，RGD-PD0325901 13相比烷氧基胺类似物，通过抑制ERK通路活性和癌细胞的DNA复制，显示出显著增强的抗肿瘤特性。此外，13在U87测定中比PD0325901显示出更强的抗增殖活性，且呈剂量依赖性。所有这些数据表明，带有酯键连接的RGD-MEKI偶联物提高了对整合素高表达肿瘤细胞的靶向能力，从而增强了抗癌疗效。
• Synthesis of fluorescent molecular probes based on cis-cinnamic acid and molecular imaging of lettuce roots
  作者：Hiroshi Fukuda、Keisuke Nishikawa、Yukihiro Fukunaga、Katsuhiro Okuda、Kozue Kodama、Kenji Matsumoto、Arihiro Kano、Mitsuru Shindo

  DOI：10.1016/j.tet.2016.08.060

  日期：2016.10

  We synthesized azo dye- and fluorescence-labeled cis-cinnamic acid analogues possessing inhibitory activity agaihst lettuce root growth and a trans-isomer without bioactivity as a control probe. The radicles incubated with the azo dye-labeled analogue were stained red, with their tips especially deeply dyed. The fluorescent images of the radicles incubated with each of these molecular probes depicted that the root cap was fluorescence-stained. However, images of the control radicles prepared by staining with the trans-isomer fluorescent probe did not show emission at the root cap. These contrasts suggest specific localization of the cis-cinnamate analogue at the columella cells. (C) 2016 Elsevier Ltd. All rights reserved.