4-Chloro-7-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-5-phenylpyrrolo[2,3-d]pyrimidin-2-amine | 848698-31-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-Chloro-7-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-5-phenylpyrrolo[2,3-d]pyrimidin-2-amine
• CAS: 848698-31-7
• 化学式: C₂₁H₂₀ClN₅O
• 分子量: 393.876
• InChiKey: AMAPWHCRXIPWMV-UHFFFAOYSA-N

物化性质

• 沸点：
  663.4±65.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  78.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-(4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)pivalamide 在 N-碘代丁二酰亚胺 、 四(三苯基膦)钯 、 苄基三乙基氯化铵 、 水 、 potassium carbonate 、 N,N-二甲基苯胺 、 zinc(II) chloride 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.67h， 生成 4-Chloro-7-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-5-phenylpyrrolo[2,3-d]pyrimidin-2-amine
  参考文献：
  名称：

  EC144 Is a Potent Inhibitor of the Heat Shock Protein 90

  摘要：

  Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that completed phase II clinical trials. Alkyne 40 is more potent than 14 in an Hsp90 alpha binding assay (IC50 = 1.1 vs 5.1 nM) as well as in its ability to degrade Her-2 in MCF-7 cells (EC50 = 14 vs 38 nM). In a mouse model of gastric tumors (N87), 40 stops tumor growth at 5 mg/kg and causes partial tumor regressions at 10 mg/kg (po, qdx5). Under the same conditions, 14 stops tumor growth only at 120 mg/kg, and does not induce partial regressions. Thus, alkyne 40 is approximately 20-fold more efficacious than 14 in mice.

  DOI：

  10.1021/jm300810x

文献信息

• Deazapurine derivatives as HSP90-Inhibitors
  申请人：Conforma Therapeutics Corporation

  公开号：EP2145888A1

  公开（公告）日：2010-01-20

  Heterobicyclic compounds of formula I are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agent. Method of synthesis and use of such compounds are also described.

  描述并证明了式 I 的杂双环化合物作为热休克蛋白 90（HSP90）抑制剂的实用性。还描述了合成和使用此类化合物的方法。
• [EN] ANTI-TUMOR METHODS USING MULTI DRUG RESISTANCE INDEPENDENT SYNTHETIC HSP90 INHIBITORS<br/>[FR] METHODES ANTITUMORALES DANS LESQUELLES SONT UTILISES DES INHIBITEURS DE HSP90 DE SYNTHESE INDEPENDANTS DE LA MULTIRESISTANCE AUX MEDICAMENTS
  申请人：CONFORMA THERAPEUTICS CORP

  公开号：WO2007035963A2

  公开（公告）日：2007-03-29

  [EN] The present invention provides a method of treating an individual having an HSP90 mediated disorder comprising administering to said individual a pharmaceutical composition comprising a pharmaceutically effective amount of a synthetic heterocyclic HSP90 inhibitor, wherein the activity of the HSP90 inhibitor is substantially independent of multi drug resistance. In one embodiment, the activity of the HSP90 inhibitor is substantially independent of P-gp and MRP expression.
  [FR] La présente invention concerne une méthode destinée au traitement d'un individu atteint d'un trouble induit par HSP90, consistant à administrer audit individu une composition pharmaceutique comprenant une dose thérapeutique d'un inhibiteur de HSP90 hétérocyclique de synthèse, l'activité de l'inhibiteur de HSP90 étant sensiblement indépendante de la multirésistance aux médicaments. Dans un mode de réalisation, l'activité de l'inhibiteur de HSP90 est sensiblement indépendante de l'expression de P-gp et MRP.
• EC144 Is a Potent Inhibitor of the Heat Shock Protein 90
  作者：Jiandong Shi、Ryan Van de Water、Kevin Hong、Ryan B. Lamer、Kenneth W. Weichert、Cristina M. Sandoval、Srinivas R. Kasibhatla、Marcus F. Boehm、Jianhua Chao、Karen Lundgren、Noelito Timple、Rachel Lough、Gerardo Ibanez、Christina Boykin、Francis J. Burrows、Marilyn R. Kehry、Theodore J. Yun、Erin K. Harning、Christine Ambrose、Jeffrey Thompson、Sarah A. Bixler、Anthone Dunah、Pamela Snodgrass-Belt、Joseph Arndt、Istvan J. Enyedy、Ping Li、Victor S. Hong、Andres McKenzie、Marco A. Biamonte

  DOI：10.1021/jm300810x

  日期：2012.9.13

  Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that completed phase II clinical trials. Alkyne 40 is more potent than 14 in an Hsp90 alpha binding assay (IC50 = 1.1 vs 5.1 nM) as well as in its ability to degrade Her-2 in MCF-7 cells (EC50 = 14 vs 38 nM). In a mouse model of gastric tumors (N87), 40 stops tumor growth at 5 mg/kg and causes partial tumor regressions at 10 mg/kg (po, qdx5). Under the same conditions, 14 stops tumor growth only at 120 mg/kg, and does not induce partial regressions. Thus, alkyne 40 is approximately 20-fold more efficacious than 14 in mice.