6-chloro-3-chloromethyl-pyridin-2-ylamine hydrochloride | 908346-42-9

• 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: 6-chloro-3-chloromethyl-pyridin-2-ylamine hydrochloride
• 英文别名: 2-amino-6-chloro-3-chloromethylpyridine hydrochloride；6-Chloro-3-(chloromethyl)pyridin-2-amine;hydrochloride；6-chloro-3-(chloromethyl)pyridin-2-amine;hydrochloride
• CAS: 908346-42-9
• 化学式: C₆H₆Cl₂N₂*ClH
• 分子量: 213.494
• InChiKey: XRODTAOCSJOPEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 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 、 6-chloro-3-chloromethyl-pyridin-2-ylamine hydrochloride 反应 0.5h， 以40%的产率得到2-[3-(2-amino-6-chloro-pyridin-3-ylmethyl)-4-methyl-thiazol-5-yl]-ethanol 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：

  (2-amino-6-chloropyridin-3-yl)methanol 在 氯化亚砜 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以92.5 g的产率得到6-chloro-3-chloromethyl-pyridin-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

• Heteroaryl substituted pyrazinyl-piperazine-piperidines with CXCR3 antagonist activity
  申请人：Zeng Qingbei

  公开号：US20060276448A1

  公开（公告）日：2006-12-07

  The present application discloses a compound, or enantiomers, stereoisomers, rotamers, tautomers, racemates or prodrug of said compound, or pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound having the general structure shown in Formula 1: and the pharmaceutically acceptable salts, solvates or esters thereof. Also disclosed is a method of treating chemokine mediated diseases, such as, palliative therapy, curative therapy, prophylactic therapy of certain diseases and conditions such as inflammatory diseases (non-limiting example(s) include, psoriasis), autoimmune diseases (non-limiting example(s) include, rheumatoid arthritis, multiple sclerosis), graft rejection (non-limiting example(s) include, allograft rejection, xenograft rejection), infectious diseases (e.g, tuberculoid leprosy), fixed drug eruptions, cutaneous delayed-type hypersensitivity responses, ophthalmic inflammation, type I diabetes, viral meningitis and tumors using a compound of Formula 1.

  本申请公开了一种化合物，或该化合物的对映体、立体异构体、转动异构体、互变异构体、外消旋体或前药，或该化合物的药物可接受的盐或溶剂，或该前药的药物可接受的盐、溶剂或酯，该化合物具有如图式1所示的一般结构，以及其药物可接受的盐、溶剂或酯。本申请还公开了一种使用图式1的化合物治疗趋化因子介导的疾病的方法，例如，缓解疗法、治愈疗法、预防疗法，如炎症性疾病（非限制性示例包括牛皮癣），自身免疫性疾病（非限制性示例包括风湿性关节炎、多发性硬化症），移植排斥（非限制性示例包括同种异体移植排斥、异种移植排斥），感染性疾病（例如，结核性麻风），固定药物性皮疹，皮肤延迟型超敏反应，眼部炎症，1型糖尿病，病毒性脑膜炎和肿瘤。
• WO2006/91428
  申请人：——

  公开号：——

  公开（公告）日：——
• HETEROARYL SUBSTITUTED PYRAZINYL-PIPERAZINE-PIPERIDINES WITH CXCR3 ANTAGONIST ACTIVITY
  申请人：Schering Corporation

  公开号：EP1858888A2

  公开（公告）日：2007-11-28
• US7879838B2
  申请人：——

  公开号：US7879838B2

  公开（公告）日：2011-02-01
• [EN] HETEROARYL SUBSTITUTED PYRAZINYL-PIPERAZINE-PIPERIDINES WITH CXCR3 ANTAGONIST ACTIVITY<br/>[FR] PYRAZINYL-PIPERAZINE-PIPERIDINES SUBSTITUTEES HETEROARYLE A ACTIVITE ANTAGONISTE CXCR3
  申请人：SCHERING CORP

  公开号：WO2006091428A2

  公开（公告）日：2006-08-31

  [EN] The present application discloses a compound, or enantiomers, stereoisomers, rotamers, tautomers, racemates or prodrug of said compound, or pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound having the general structure shown in Formula 1 and the pharmaceutically acceptable salts, solvates or esters thereof. Also disclosed is a method of treating chemokine mediated diseases, such as, palliative therapy, curative therapy, prophylactic therapy of certain diseases and conditions such as inflammatory diseases (non limiting example(s) include, psoriasis), autoimmune diseases (non limiting example(s) include, rheumatoid arthritis, multiple sclerosis), graft rejection (non limiting example(s) include, allograft rejection, xenograft rejection), infectious diseases (e.g , tuberculoid leprosy), fixed drug eruptions, cutaneous delayed type hypersensitivity responses, ophthalmic inflammation, type I diabetes, viral meningitis and tumors using a compound of Formula 1.
  [FR] La présente invention concerne un composé, ou des énantiomères, des stéréoisomères, des rotamères, das tautomères, des racémates ou un promédicament dudit composé, ou des sels, des solvates ou des esters acceptables d'un poids de vue pharmaceutique dudit composé, ou dudit promédicament, ledit composé présentant la structure générale représentée par la formule 1 ou un sel, solvate, ou ester acceptable d'un point de vue pharmaceutique de celui-ci. L'invention concerne également une méthode de traitement des maladies médiées par les chimiokines, par exemple la thérapie palliative, la thérapie curative, la thérapie prophylactique de certaines maladies et états tels que les maladies inflammatoires (par exemple, entre autres, le psoriasis), les maladies autoimmunes (par exemple, entre autres, la polyarthrite rhumatoïde et la sclérose en plaques), un rejet de greffe (par exemple, entre autres, un rejet de greffe allogénique ou un rejet de xénogreffe), les maladies infectieuses (par exemple la lèpre tuberculoïde), les éruptions médicamenteuses fixes, des réponses d'hypersensibilité cutanée retardées, les inflammations ophtalmiques, le diabète de type I, la méningite virale et les tumeurs, à l'aide des composés représentés par la formule 1.