N1-methyl-N3-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine | 1143459-76-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N1-methyl-N3-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine
• 英文别名: N-methyl-N'-(4-(pyridin-3-yl)pyrimidin-2-yl)-benzene-1,3-diamine；1-N-methyl-3-N-(4-pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine
• CAS: 1143459-76-0
• 化学式: C₁₆H₁₅N₅
• 分子量: 277.329
• InChiKey: XYPIKSHJRTYMQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  62.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N1-methyl-N3-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine 、 4-((2-((tert-butoxycarbonyl)amino)phenyl)carbamoyl)benzoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 以27%的产率得到tert-butyl 2-(4-(methyl(3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)carbamoyl)benzamido)phenylcarbamate
  参考文献：
  名称：

  [EN] NOVEL BIFUNCTIONAL COMPOUNDS WHICH INHIBIT PROTEIN KINASES AND HISTONE DEACETYLASES
  [FR] NOUVEAUX COMPOSÉS BIFONCTIONNELS QUI INHIBENT LES PROTÉINES KINASES ET LES HISTONES DÉSACÉTYLASES

  摘要：

  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。

  公开号：

  WO2009063054A1
• 作为产物：
  描述：

  聚合甲醛 、 1,3-苯二胺,N-[4-(3-吡啶基)-2-嘧啶基]- 在 sodium methylate 、 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以93%的产率得到N1-methyl-N3-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine
  参考文献：
  名称：

  [EN] NOVEL BIFUNCTIONAL COMPOUNDS WHICH INHIBIT PROTEIN KINASES AND HISTONE DEACETYLASES
  [FR] NOUVEAUX COMPOSÉS BIFONCTIONNELS QUI INHIBENT LES PROTÉINES KINASES ET LES HISTONES DÉSACÉTYLASES

  摘要：

  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。

  公开号：

  WO2009063054A1

文献信息

• 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.
• [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。