5-chloromethylpyridin-2-ylamine hydrochloride | 866561-43-5

• 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
• 英文名称: 5-chloromethylpyridin-2-ylamine hydrochloride
• 英文别名: 5-(Chloromethyl)pyridin-2-amine hydrochloride；5-(chloromethyl)pyridin-2-amine;hydrochloride
• CAS: 866561-43-5
• 化学式: C₆H₇ClN₂*ClH
• 分子量: 179.049
• InChiKey: LGUMYAZLHLBVHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.82
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  38.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-甲基-5-(beta-羟乙基)噻唑 、 5-chloromethylpyridin-2-ylamine hydrochloride 反应 0.5h， 以42%的产率得到3-(6-aminopyridin-3-ylmethyl)-5-(2-hydroxyethyl)-4-methylthiazol-3-ium chloride hydrochloride
  参考文献：
  名称：

  Synthesis, in vitro and in vivo activity of thiamine antagonist transketolase inhibitors

  摘要：

  Tumor cells extensively utilize the pentose phosphate pathway for the synthesis of ribose. Transketolase is a key enzyme in this pathway and has been suggested as a target for inhibition in the treatment of cancer. In a pharmacodynamic study, nude mice with xenografted HCT-116 tumors were dosed with 1 ('N3'-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxyethyl)-4-methyl-thiazol-3-ium chloride hydrochloride), an analog of thiamine, the co-factor of transketolase. Transketolase activity was almost completely suppressed in blood, spleen, and tumor cells, but there was little effect on the activity of the other thiamine-utilizing enzymes alpha-ketoglutarate dehydrogenase or glucose-6-phosphate dehydrogenase. Synthesis and SAR of transketolase inhibitors is described. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.101
• 作为产物：
  描述：

  6-氨基-3-吡啶基甲醇 在 氯化亚砜 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以60%的产率得到5-chloromethylpyridin-2-ylamine hydrochloride
  参考文献：
  名称：

  Synthesis, in vitro and in vivo activity of thiamine antagonist transketolase inhibitors

  摘要：

  Tumor cells extensively utilize the pentose phosphate pathway for the synthesis of ribose. Transketolase is a key enzyme in this pathway and has been suggested as a target for inhibition in the treatment of cancer. In a pharmacodynamic study, nude mice with xenografted HCT-116 tumors were dosed with 1 ('N3'-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxyethyl)-4-methyl-thiazol-3-ium chloride hydrochloride), an analog of thiamine, the co-factor of transketolase. Transketolase activity was almost completely suppressed in blood, spleen, and tumor cells, but there was little effect on the activity of the other thiamine-utilizing enzymes alpha-ketoglutarate dehydrogenase or glucose-6-phosphate dehydrogenase. Synthesis and SAR of transketolase inhibitors is described. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.101

文献信息

• [EN] THIAZOLIUMS AS TRANSKETOLASE INHIBITORS<br/>[FR] THIAZOLIUMS COMME INHIBITEURS DE LA TRANSCETOLASE
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2005095391A1

  公开（公告）日：2005-10-13

  The present invention provides N-3'-pyridylmethyl or N-2'-pyrazinylmethyl thiazolium derivatives of formula (I) which are useful as transketolase inhibitors wherein R1, R2, R3, Y, R5-R9, Ra-Rd, n and X- are as defined herein. The present invention also provides pharmaceutical compositions comprising the compounds of formula (I). The invention provides methods for inhibiting transketolase activity, reducing cellular ribose-5-phosphate levels, inhibiting nucleic acid synthesis, inhibiting cell proliferation and tumor cell growth in vitro and in vivo, stimulating apoptosis in tumor cells and treating cancer by administering a compound of formula (I) or a pharmaceutical composition thereof.

  本发明提供了公式（I）的N-3'-吡啶甲基或N-2'-吡嗪甲基噻唑衍生物，其作为转醛酮酶抑制剂是有用的，其中R1、R2、R3、Y、R5-R9、Ra-Rd、n和X-如本文所定义。本发明还提供了包括公式（I）化合物的药物组合物。该发明提供了抑制转醛酮酶活性、降低细胞核糖-5-磷酸水平、抑制核酸合成、抑制体外和体内细胞增殖和肿瘤细胞生长、刺激肿瘤细胞凋亡以及通过给予公式（I）的化合物或其药物组合物来治疗癌症的方法。
• Thiazoliums as transketolase inhibitors
  申请人：Boyd Steven A.

  公开号：US20090209554A1

  公开（公告）日：2009-08-20

  The present invention provides N-3′-pyridyl-methyl or N-2′-pyrazinylmethyl thiazolium derivatives of formula (I) which are useful as transketolase inhibitors wherein R 1 , R 2 , R 3 , Y, R 5 -R 9 , R a -R d , n and X − are as defined herein. The present invention also provides pharmaceutical compositions comprising the compounds of formula (I). The invention provides methods for inhibiting transketolase activity, reducing cellular ribose-5-phosphate levels, inhibiting nucleic acid synthesis, inhibiting cell proliferation and tumor cell growth in vitro and in vivo, stimulating apoptosis in tumor cells and treating cancer by administering a compound of formula (I) or a pharmaceutical composition thereof.

  本发明提供了式（I）的N-3'-吡啶甲基或N-2'-吡嗪甲基噻唑盐衍生物，其作为转酮糖酶抑制剂是有用的，其中R1、R2、R3、Y、R5-R9、Ra-Rd、n和X-如本文所定义。本发明还提供了包含式（I）的化合物的制药组合物。本发明提供了通过给予式（I）的化合物或其制药组合物来抑制转酮糖酶活性、降低细胞核糖-5-磷酸水平、抑制核酸合成、抑制细胞增殖和肿瘤细胞在体内和体外生长、刺激肿瘤细胞凋亡和治疗癌症的方法。
• Synthesis, in vitro and in vivo activity of thiamine antagonist transketolase inhibitors
  作者：Allen A. Thomas、Y. Le Huerou、J. De Meese、Indrani Gunawardana、Tomas Kaplan、Todd T. Romoff、Stephen S. Gonzales、Kevin Condroski、Steven A. Boyd、Josh Ballard、Bryan Bernat、Walter DeWolf、May Han、Patrice Lee、Christine Lemieux、Robin Pedersen、Jed Pheneger、Greg Poch、Darin Smith、Francis Sullivan、Solly Weiler、S. Kirk Wright、Jie Lin、Barb Brandhuber、Guy Vigers

  DOI：10.1016/j.bmcl.2007.11.101

  日期：2008.3

  Tumor cells extensively utilize the pentose phosphate pathway for the synthesis of ribose. Transketolase is a key enzyme in this pathway and has been suggested as a target for inhibition in the treatment of cancer. In a pharmacodynamic study, nude mice with xenografted HCT-116 tumors were dosed with 1 ('N3'-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxyethyl)-4-methyl-thiazol-3-ium chloride hydrochloride), an analog of thiamine, the co-factor of transketolase. Transketolase activity was almost completely suppressed in blood, spleen, and tumor cells, but there was little effect on the activity of the other thiamine-utilizing enzymes alpha-ketoglutarate dehydrogenase or glucose-6-phosphate dehydrogenase. Synthesis and SAR of transketolase inhibitors is described. (C) 2007 Elsevier Ltd. All rights reserved.