methyl 4-{4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenylaminomethyl}benzoate | 1026788-31-7

• 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: methyl 4-{4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenylaminomethyl}benzoate
• 英文别名: methyl 4-[({4-methyl-3-[(4-pyridine-3-ylpyrimidine-2-yl)amino]phenyl}amino)methyl]benzoate；4-{[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenylamino]-methyl}-benzoic acid methyl ester；Methyl 4-[({4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenyl}amino)methyl]benzoate；methyl 4-[[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]anilino]methyl]benzoate
• CAS: 1026788-31-7
• 化学式: C₂₅H₂₃N₅O₂
• 分子量: 425.49
• InChiKey: KGVCNWNMZFPZRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  89
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 4-{4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenylaminomethyl}benzoate 在 盐酸羟胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以86%的产率得到N-hydroxy-4-({4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenylamino}methyl)benzamide
  参考文献：
  名称：

  2-（芳基氨基）嘧啶系列官能化酰胺的合成

  摘要：

  合成了2-（芳基氨基）嘧啶系列的新酰胺，其中酪氨酸激酶的药效学片段和组蛋白脱乙酰基酶抑制剂和官能团可提供化合物在纳米载体上的化学吸附。

  DOI：

  10.1134/s1070428017020191
• 作为产物：
  描述：

  methyl 4-{4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenyliminomethyl}benzoate 在 sodium tetrahydroborate 、 溶剂黄146 、 吡啶 、 sodium hydroxide 作用下， 以 氯仿 、 水 为溶剂， 反应 6.0h， 以95%的产率得到methyl 4-{4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenylaminomethyl}benzoate
  参考文献：
  名称：

  Preparative synthesis of heterocyclic and aromatic N-benzyl amines

  摘要：

  A simple and highly efficient procedure has been proposed for the synthesis of heterocyclic and aromatic N-benzyl amines via reductive amination of substituted aromatic aldehydes in the presence of sodium tetrahydridoborate-acetic acid system generating reactive sodium triacetoxyhydridoborate.

  DOI：

  10.1134/s107042801304012x

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。
• 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.
• Synthesis of N-[2(3,4)-aminophenyl]-4-({4-methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenyl}aminomethyl)benzamides
  作者：Zh. V. Ignatovich、Yu. V. Sinyutich、K. N. Gusak、E. V. Koroleva

  DOI：10.1134/s1070428015100164

  日期：2015.10

  New N-[2(3,4)-aminophenyl]benzamides containing a pharmacophoric 2-(arylamino)pyrimidine fragment have been synthesized from the corresponding substituted benzoic acid.