N1-(4-methyl-3-(4-(pyridin-3-yl)thiazol-2-ylamino)phenyl)-N4-(tetrahydro-2H-pyran-2-yloxy)terephthalamide | 1143460-23-4

• 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: N1-(4-methyl-3-(4-(pyridin-3-yl)thiazol-2-ylamino)phenyl)-N4-(tetrahydro-2H-pyran-2-yloxy)terephthalamide
• 英文别名: 1-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]-4-N-(oxan-2-yloxy)benzene-1,4-dicarboxamide
• CAS: 1143460-23-4
• 化学式: C₂₈H₂₇N₅O₄S
• 分子量: 529.619
• InChiKey: DVSUTHCUKILBTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  143
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N1-(4-methyl-3-(4-(pyridin-3-yl)thiazol-2-ylamino)phenyl)-N4-(tetrahydro-2H-pyran-2-yloxy)terephthalamide 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 16.0h， 以70%的产率得到N1-hydroxy-N4-(4-methyl-3-(4-(pyridin-3-yl)thiazol-2-ylamino)phenyl)terephthalamide hydrochloride
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm800988r
• 作为产物：
  描述：

  O-(四氢-2H-吡喃-2-基)羟基胺 、 4-(4-methyl-3-(4-(pyridin-3-yl)thiazol-2-ylamino)phenylcarbamoyl)benzoic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以60%的产率得到N1-(4-methyl-3-(4-(pyridin-3-yl)thiazol-2-ylamino)phenyl)-N4-(tetrahydro-2H-pyran-2-yloxy)terephthalamide
  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