methyl 4-((2-((tert-butoxycarbonyl)amino)phenyl)carbamoyl)benzoate | 209785-16-0

• 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: methyl 4-((2-((tert-butoxycarbonyl)amino)phenyl)carbamoyl)benzoate
• 英文别名: N-(2-t-Butoxycarbonylaminophenyl)-4-methoxycarbonylbenzamide；methyl 4-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]carbamoyl]benzoate
• CAS: 209785-16-0
• 化学式: C₂₀H₂₂N₂O₅
• 分子量: 370.405
• InChiKey: JPMPMOVZBIBRMQ-UHFFFAOYSA-N

物化性质

• 熔点：
  145.5-146.5 °C
• 沸点：
  421.8±30.0 °C(Predicted)
• 密度：
  1.254±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-((2-((tert-butoxycarbonyl)amino)phenyl)carbamoyl)benzoate 在 二异丁基氢化铝 作用下， 以 四氢呋喃 为溶剂， 生成 tert-butyl (2-(4-(hydroxymethyl)benzamido)phenyl)carbamate
  参考文献：
  名称：

  4-(Heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs as a novel class of histone deacetylase inhibitors

  摘要：

  The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs is described. Some of these compounds were shown to inhibit HDAC1 with IC50 values below the micromolar range, induce hyperacetylation of histones, upregulate expression of the tumor suppressor p21(WAF1/Cip1), and inhibit proliferation of human cancer cells. In addition, certain compounds of this class were active in several human tumor xenograft models in vivo. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.12.057
• 作为产物：
  描述：

  对苯二甲酸单甲酯 在 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 methyl 4-((2-((tert-butoxycarbonyl)amino)phenyl)carbamoyl)benzoate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of colchicine derivatives as novel tubulin and histone deacetylase dual inhibitors

  摘要：

  A new class of colchicine derivatives were designed and synthesized as tubulin-HDAC dual inhibitors. Biological evaluations of these hybrids included the inhibitory activity of HDAC, tubulin polymerization analysis, in vitro cell cycle analysis in HCT-116 cells and cytotoxicity against different cancer cell lines. Hybrid 6d behaved as potent HDAC-tubulin dual inhibitor and showed comparable cytotoxicity with colchicine. Compound ha exhibited powerful tubulin inhibitory activity, moderate anti-HDAC activity and the most potent cytotoxicity (IC50 = 2-105 nM). (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.035

文献信息

• Discovery of Novel Indoleamine 2,3-Dioxygenase 1 (IDO1) and Histone Deacetylase (HDAC) Dual Inhibitors
  作者：Kun Fang、Guoqiang Dong、Yu Li、Shipeng He、Ying Wu、Shanchao Wu、Wei Wang、Chunquan Sheng

  DOI：10.1021/acsmedchemlett.7b00487

  日期：2018.4.12

  order to take advantage of both immunotherapeutic and epigenetic antitumor agents, the first generation of dual indoleamine 2,3-dioxygenase 1 (IDO1) and histone deacetylase (HDAC) inhibitors were designed. The highly active dual inhibitor 10 showed excellent and balanced activity against both IDO1 (IC50 = 69.0 nM) and HDAC1 (IC50 = 66.5 nM), whose dual targeting mechanisms were validated in cancer cells

  为了同时利用免疫治疗和表观遗传抗肿瘤药，设计了第一代双吲哚胺2,3-二加氧酶1（IDO1）和组蛋白脱乙酰基酶（HDAC）抑制剂。高活性双重抑制剂10对IDO1（IC50 = 69.0 nM）和HDAC1（IC50 = 66.5 nM）均显示出优异且平衡的活性，其双重靶向机制已在癌细胞中得到验证。化合物10作为口服活性抗肿瘤药具有良好的药代动力学特征，并显着降低了血浆中的鸟尿素水平。特别地，它在鼠LLC肿瘤模型中显示出优异的体内抗肿瘤功效，且毒性低。这项概念验证研究为癌症治疗提供了一种新颖的策略。
• [EN] NOVEL BIFUNCTIONAL COMPOUNDS WHICH INHIBIT PROTEIN KINASES AND HISTONE DEACETYLASES<br/>[FR] NOUVEAUX COMPOSÉS BIFONCTIONNELS QUI INHIBENT LES PROTÉINES KINASES ET LES HISTONES DÉSACÉTYLASES
  申请人：4SC AG

  公开号：WO2009063054A1

  公开（公告）日：2009-05-22

  The present invention relates to a bifunctional compound of formula I or its pharmaceutically acceptable salts or solvates A-L-B (I) wherein A is a histone deacetylase (HDAC) inhibitory moiety, L is a single bond or a linker group and B is a protein kinase inhibitory moiety. The bifunctional compound according to formula (I) is useful for the treatment of malignant and non-malignant neoplasia and diseases related to abnormal cell growth.

  本发明涉及公式I的双功能化合物或其药用可接受的盐或溶剂A-L-B（I），其中A是组蛋白去乙酰化酶（HDAC）抑制基团，L是单键或连接基团，B是蛋白激酶抑制基团。根据公式（I）的双功能化合物可用于治疗恶性和非恶性肿瘤以及与异常细胞生长相关的疾病。
• [EN] INHIBITORS OF HISTONE DEACETYLASE<br/>[FR] INHIBITEURS DE L'HISTONE DEACETYLASE
  申请人：METHYLGENE INC

  公开号：WO2004069823A1

  公开（公告）日：2004-08-19

  The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

  该发明涉及抑制组蛋白去乙酰化酶的技术。该发明提供了抑制组蛋白去乙酰化酶酶活性的化合物和方法。该发明还提供了治疗细胞增殖性疾病和病症的组合物和方法。
• Cell differentiation inducer
  申请人：Schering Aktiengesellschaft

  公开号：US20040147569A1

  公开（公告）日：2004-07-29

  The novel benzamide derivative represented by formula (1) and the novel anilide derivative represented by formula (13) of this invention has differentiation-inducing effect, and are, therefore, useful a therapeutic or improving agent for malignant tumors, autoimmune diseases, dermatologic diseases and parasitism. In particular, they are highly effective as an anticancer drug, specifically to a hematologic malignancy and a solid carcinoma. 1

  本发明中由公式（1）表示的新型苯甲酰胺衍生物和由公式（13）表示的新型苯胺酰衍生物具有诱导分化的效果，因此可用作恶性肿瘤、自身免疫性疾病、皮肤病和寄生虫治疗或改善剂。特别是，它们对于血液恶性肿瘤和实体癌具有高度的抗癌药物效果。
• Inhibitors of Histone Deacetylase
  申请人：Delorme Daniel

  公开号：US20070213330A1

  公开（公告）日：2007-09-13

  The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

  本发明涉及抑制组蛋白去乙酰化酶的技术。本发明提供了抑制组蛋白去乙酰化酶酶活性的化合物和方法。本发明还提供了治疗细胞增殖性疾病和病况的组合物和方法。