methyl 5-(2-(tert-butoxycarbonylamino)phenylcarbamoyl)thiophene-2-carboxylate | 742070-17-3

• 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 5-(2-(tert-butoxycarbonylamino)phenylcarbamoyl)thiophene-2-carboxylate
• 英文别名: 5-(2-tert-butoxycarbonylamino-phenylcarbamoyl)-thiophene-2-carboxylic acid methyl ester；methyl 5-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]carbamoyl]thiophene-2-carboxylate
• CAS: 742070-17-3
• 化学式: C₁₈H₂₀N₂O₅S
• 分子量: 376.433
• InChiKey: PORRLJWBPFQHCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  122
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 5-(2-(tert-butoxycarbonylamino)phenylcarbamoyl)thiophene-2-carboxylate 在 水 、 lithium hydroxide 作用下， 以 甲醇 为溶剂， 以77%的产率得到5-((2-((tert-butoxycarbonyl)amino)phenyl)carbamoyl)thiophene-2-carboxylic acid
  参考文献：
  名称：

  发现新型吲哚胺2,3-双加氧酶1（IDO1）和组蛋白脱乙酰基酶（HDAC）双重抑制剂。

  摘要：

  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。

  DOI：

  10.1021/acsmedchemlett.7b00487
• 作为产物：
  描述：

  N-Boc-1,2-亚苯基二胺 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 methyl 5-(2-(tert-butoxycarbonylamino)phenylcarbamoyl)thiophene-2-carboxylate
  参考文献：
  名称：

  [EN] MONO-ACYLATED O-PHENYLENDIAMINES DERIVATIVES AND THEIR USE AGAINST CANCER
  [FR] NOUVEAUX DÉRIVÉS D'O-PHÉNYLENDIAMINES MONOACYLÉES

  摘要：

  公开号：

  WO2004069803A3

文献信息

• [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。
• Mono-acylated o-phenylendiamines derivatives
  申请人：Fertig Georg

  公开号：US20060089403A1

  公开（公告）日：2006-04-27

  Mono-acylated o-phenylendiamines derivatives of formula A: which are useful for the treatment of diseases mediated by the inhibition of histone deacetylase, such as cancer.

  公式A的单酰化的邻苯二胺衍生物，可用于治疗通过抑制组蛋白去乙酰化酶介导的疾病，如癌症。
• NOVEL BIFUNCTIONAL COMPOUNDS WHICH INHIBIT PROTEIN KINASES AND HISTONE DEACETYLASES
  申请人：Bar Thomas

  公开号：US20110065734A1

  公开（公告）日：2011-03-17

  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.

  本发明涉及一种式I的双功能化合物或其药学上可接受的盐或溶剂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。根据式（I）的双功能化合物对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非常有用。
• Novel bifunctional compounds which inhibit protein kinases and histone deacetylases
  申请人：4SC AG

  公开号：EP2060565A1

  公开（公告）日：2009-05-20

  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.

  本发明涉及式 I 的双官能团化合物或其药学上可接受的盐或溶解物 A-L-B (I) 其中 A 是组蛋白去乙酰化酶（HDAC）抑制分子，L 是单键或连接基团，B 是蛋白激酶抑制分子。根据式（I）的双功能化合物可用于治疗恶性和非恶性肿瘤以及与细胞异常生长有关的疾病。
• Design of Chimeric Histone Deacetylase- and Tyrosine Kinase-Inhibitors: A Series of Imatinib Hybrides as Potent Inhibitors of Wild-Type and Mutant BCR-ABL, PDGF-Rβ, and Histone Deacetylases
  作者：Siavosh Mahboobi、Stefan Dove、Andreas Sellmer、Matthias Winkler、Emerich Eichhorn、Herwig Pongratz、Thomas Ciossek、Thomas Baer、Thomas Maier、Thomas Beckers

  DOI：10.1021/jm800988r

  日期：2009.4.23

  Inhibitors of histone deacetylases are a new class of cancer therapeutics with possibly broad applicability. Combinations of HDAC inhibitors with the kinase inhibitor 1 (Imatimb) in recent studies showed additive and synergistic effects. Here we present a new concept by combining inhibition of protein kinases and HDACs, two independent pharmacological activities, in one synthetic small molecule. In general, the HDAC inhibition profile, the potencies, and the probable binding modes to HDAC1 and HDAC6 were similar as for 6 (SAHA). Inhibition of AN kinase in biochemical assays was maintained for Most compounds, but in general the kinase selectivity profile differed from that of I with nearly equipotent inhibition of the wildtype and the Imatimb resistant Abl (TI)-I-315 mutant. A potent cellular inhibition of PDGFR and cytotoxicity toward EOL-1 cells, a model for idiopathic hypereosinophilic syndrome (HES), are restored or enhanced for selected analogues (12b, 14b, and 18b). Cytotoxicity was evaluated by using a broad panel Of tumor cell lines, with selected analogues displaying mean IC50 values between 3.6 and 7.1 mu M.