5-(氯甲基)-2,4-二甲基-3-羟基吡啶 | 791724-87-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 5-(氯甲基)-2,4-二甲基-3-羟基吡啶
• 英文名称: 5-chloromethyl-2,4-dimethyl-pyridin-3-ol
• 英文别名: 5-Chlormethyl-2,4-dimethyl-pyridin-3-ol；5-(Chloromethyl)-2,4-dimethylpyridin-3-ol
• CAS: 791724-87-3
• 化学式: C₈H₁₀ClNO
• 分子量: 171.626
• InChiKey: ARBQITPFCCDXTA-UHFFFAOYSA-N

物化性质

• 沸点：
  380.3±37.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 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)-2,4-二甲基-3-羟基吡啶 在 偶氮二甲酸二异丙酯 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 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 肼 、 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-(氯甲基)-2,4-二甲基-3-羟基吡啶
  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

• In-vitro antitumor activity of new quaternary phosphonium salts, derivatives of 3-hydroxypyridine
  作者：Alfiya G. Iksanova、Raylya R. Gabbasova、Tatyana V. Kupriyanova、Almaz A. Akhunzyanov、Michail V. Pugachev、Ruzalia M. Vafiva、Nikita V. Shtyrlin、Konstantin V. Balakin、Yurii G. Shtyrlin

  DOI：10.1097/cad.0000000000000642

  日期：2018.8

  ovarian adenocarcinoma cells OVCAR-4 with the tested compounds inhibited the growth and induced cell cycle arrest in the G1 phase. 3-Hydroxypyridine derivatives induced apoptosis by hyperexpression of Bax and caspase-3, whereas 4-deoxypyridoxine derivative induced cell death partly by reactive oxygen species generation and caspase-3 hyperexpression. These results indicate that the quaternary phosphonium

  这项工作提出了三种新型抗癌药，基于3-羟基吡啶骨架的phospho盐，包括一种4-脱氧吡啶酮的体外生物活性研究的结果。通过集落形成和3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物分析评估用这些化合物处理的细胞的增殖和活力。分别通过膜联蛋白V-FITC /碘化丙啶和碘化丙啶染色的流式细胞术研究了这些化合物对细胞凋亡和细胞周期的影响。使用四甲基若丹明乙基和DCFHA染色评估了化合物对线粒体膜电位和细胞内活性氧种类的影响。Western印迹分析用于研究Bcl-xL，Bax和caspase-3凋亡蛋白表达的变化。用受试化合物处理卵巢腺癌细胞OVCAR-4可以抑制生长，并诱导G1期细胞周期停滞。3-Hydroxypyridine衍生物通过Bax和caspase-3的过表达诱导细胞凋亡，而4-deoxypyridoxine衍生物部分通过活性氧的产生和caspase-3的过表达诱导细胞死亡
• Pharmaceutical composition containing, as active ingredient, 7-azaindolin-2-one derivative or pharmaceutically acceptable salt thereof
  申请人：LG CHEM, LTD.

  公开号：US10544140B2

  公开（公告）日：2020-01-28

  7-azaindolin-2-one derivatives of Formula 1 or pharmaceutically acceptable salts thereof, a pharmaceutical composition comprising them for preventing or treating a cancer, and a method for preparing them.

  式 1 的 7-氮杂吲哚啉-2-酮衍生物 或其药学上可接受的盐、包含它们的用于预防或治疗癌症的药物组合物，以及制备它们的方法。
• The Synthesis of Compounds for the Chemotherapy of Tuberculosis. I. Heterocyclic Thiosemicarbazide Derivatives
  作者：Thomas S. Gardner、F. A. Smith、E. Wenis、John Lee

  DOI：10.1021/jo50001a015

  日期：1951.7
• Nitrogen Mustards
  作者：Evelyn Wilson、Max Tishler

  DOI：10.1021/ja01152a023

  日期：1951.8
• Rationally Designed High-Affinity 2-Amino-6-halopurine Heat Shock Protein 90 Inhibitors That Exhibit Potent Antitumor Activity
  作者：Srinivas R. Kasibhatla、Kevin Hong、Marco A. Biamonte、David J. Busch、Patricia L. Karjian、John L. Sensintaffar、Adeela Kamal、Rachel E. Lough、John Brekken、Karen Lundgren、Roy Grecko、Gregg A. Timony、Yingqing Ran、Robert Mansfield、Lawrence C. Fritz、Edgar Ulm、Francis J. Burrows、Marcus F. Boehm

  DOI：10.1021/jm050752+

  日期：2007.6.1

  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.