5-氯甲基-3-甲氧基-2,4-二甲基吡啶 | 943315-20-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 5-氯甲基-3-甲氧基-2,4-二甲基吡啶
• 英文名称: 5-chloromethyl-3-methoxy-2,4-dimethylpyridine
• 英文别名: 5-(chloromethyl)-3-methoxy-2,4-dimethylpyridine
• CAS: 943315-20-6
• 化学式: C₉H₁₂ClNO
• 分子量: 185.653
• InChiKey: NADPTRXTYCEQRY-UHFFFAOYSA-N

物化性质

• 沸点：
  278.1±35.0 °C(Predicted)
• 密度：
  1.112±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  5-氯甲基-3-甲氧基-2,4-二甲基吡啶 、 2-氨基-6-氯嘌呤 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以82%的产率得到6-chloro-9-(5-methoxy-4,6-dimethyl-pyridin-3-ylmethyl)-9H-purin-2-ylamine
  参考文献：
  名称：

  Rationally Designed High-Affinity 2-Amino-6-halopurine Heat Shock Protein 90 Inhibitors That Exhibit Potent Antitumor Activity

  摘要：

  Heat shock protein 90 (Hsp90) is a molecular chaperone protein implicated in stabilizing the conformation and maintaining the function of many cell-signaling proteins. Many oncogenic proteins are more dependent on Hsp90 in maintaining their conformation, stability, and maturation than their normal counterparts. Furthermore, recent data show that Hsp90 exists in an activated form in malignant cells but in a latent inactive form in normal tissues, suggesting that inhibitors selective for the activated form could provide a high therapeutic index. Hence, Hsp90 is emerging as an exciting new target for the treatment of cancer. We now report on a novel series of 2-amino-6-halopurine Hsp90 inhibitors exemplified by 2-amino-6-chloro-9-(4-iodo-3,5-dimethylpyridin-2-ylmethyl)purine (30). These highly potent inhibitors (IC50 of 30 = 0.009 mu M in a HER-2 degradation assay) also display excellent antiproliferative activity against various tumor cell lines (IC50 of 30 = 0.03 mu M in MCF7 cells). Moreover, this class of inhibitors shows higher affinity for the activated form of Hsp90 compared to our earlier 8-sulfanylpurine Hsp90 inhibitor series. When administered orally to mice, these compounds exhibited potent tumor growth inhibition (> 80%) in an N87 xenograft model, similar to that observed with 17-allylamino-17-desmethoxygeldanamycin (17-AAG), which is a compound currently in phase I/II clinical trials.

  DOI：

  10.1021/jm050752+
• 作为产物：
  描述：

  吡哆醇盐酸盐 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 肼 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 5-氯甲基-3-甲氧基-2,4-二甲基吡啶
  参考文献：
  名称：

  Rationally Designed High-Affinity 2-Amino-6-halopurine Heat Shock Protein 90 Inhibitors That Exhibit Potent Antitumor Activity

  摘要：

  Heat shock protein 90 (Hsp90) is a molecular chaperone protein implicated in stabilizing the conformation and maintaining the function of many cell-signaling proteins. Many oncogenic proteins are more dependent on Hsp90 in maintaining their conformation, stability, and maturation than their normal counterparts. Furthermore, recent data show that Hsp90 exists in an activated form in malignant cells but in a latent inactive form in normal tissues, suggesting that inhibitors selective for the activated form could provide a high therapeutic index. Hence, Hsp90 is emerging as an exciting new target for the treatment of cancer. We now report on a novel series of 2-amino-6-halopurine Hsp90 inhibitors exemplified by 2-amino-6-chloro-9-(4-iodo-3,5-dimethylpyridin-2-ylmethyl)purine (30). These highly potent inhibitors (IC50 of 30 = 0.009 mu M in a HER-2 degradation assay) also display excellent antiproliferative activity against various tumor cell lines (IC50 of 30 = 0.03 mu M in MCF7 cells). Moreover, this class of inhibitors shows higher affinity for the activated form of Hsp90 compared to our earlier 8-sulfanylpurine Hsp90 inhibitor series. When administered orally to mice, these compounds exhibited potent tumor growth inhibition (> 80%) in an N87 xenograft model, similar to that observed with 17-allylamino-17-desmethoxygeldanamycin (17-AAG), which is a compound currently in phase I/II clinical trials.

  DOI：

  10.1021/jm050752+

文献信息

• [EN] CERTAIN SUBSTITUTED PYRIMIDINES, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS FOR THEIR USE<br/>[FR] CERTAINES PYRIMIDINES SUBSTITUÉES, LEURS COMPOSITIONS PHARMACEUTIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：BIOGEN IDEC INC

  公开号：WO2010117425A1

  公开（公告）日：2010-10-14

  Provided are certain Hsp90 inhibitors, i.e., compounds of Formula I and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods for their use and preparation.

  提供了某些Hsp90抑制剂，即Formula I的化合物及其药用盐、药物组合物以及它们的使用和制备方法。
• 7,9-Dihydro-Purin-8-One and Related Analogs as HSP90-Inhibitors
  申请人：Le Brazidec Jean-Yves

  公开号：US20070253896A1

  公开（公告）日：2007-11-01

  The invention relates in general to 7,9-dihydro-purin-8-one and related compounds that show broad utility, e.g., in inhibiting heat shock protein 90 (HSP90) to thereby treat or prevent HSP90-mediated diseases.

  本发明一般涉及7,9-二氢嘌呤-8-酮及相关化合物，这些化合物显示出广泛的用途，例如抑制热休克蛋白90（HSP90），从而治疗或预防HSP90介导的疾病。
• 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.
• 7,9-DIHYDRO-PURIN-8-ONE AND RELATED ANALOGS AS HSP90-INHIBITORS
  申请人：Conforma Therapeutics Corporation

  公开号：EP2012791A2

  公开（公告）日：2009-01-14
• [EN] 7,9-DIHYDRO-PURIN-8-ONE AND RELATED ANALOGS AS HSP90-INHIBITORS<br/>[FR] 7,9-DIHYDRO-PURIN-8-ONE ET ANALOGUES ASSOCIÉS UTILISÉS EN TANT QU'INHIBITEURS DE HSP90
  申请人：CONFORMA THERAPEUTICS CORP

  公开号：WO2007092496A2

  公开（公告）日：2007-08-16

  [EN] The invention relates in general to 7,9-dihydro-purin-8-one and related compounds that show broad utility, e.g., in inhibiting heat shock protein 90 (HSP90) to thereby treat or prevent HSP90-mediated diseases.
  [FR] L'invention concerne, de manière générale, du 7,9-dihydro-purin-8-one et des composés associés présentant une grande utilité, par exemple, dans l'inhibition de la protéine 90 de choc thermique (HSP90), en vue de traiter ou prévenir des maladies induites par HSP90.