methyl 3-amino-6-chloro-5-[(3S)-3-ethyl-4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]piperazin-1-yl]pyrazine-2-carboxylate | 907181-40-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: methyl 3-amino-6-chloro-5-[(3S)-3-ethyl-4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]piperazin-1-yl]pyrazine-2-carboxylate
• CAS: 907181-40-2
• 化学式: C₂₂H₃₅ClN₆O₄
• 分子量: 483.011
• InChiKey: BWYIYCBBIKJZNQ-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 3-amino-6-chloro-5-[(3S)-3-ethyl-4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]piperazin-1-yl]pyrazine-2-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 3-amino-6-chloro-5-[(3S)-3-ethyl-4-piperidin-4-ylpiperazin-1-yl]pyrazine-2-carboxylate
  参考文献：
  名称：

  III. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl–piperazinyl–piperidine scaffold

  摘要：

  The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. Compound 16e with single-digit CXCR3 affinity, good rat PK and hERG profiles has been identified as a lead for further study. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.120
• 作为产物：
  描述：

  3-氨基-5,6-二氯-2-吡嗪羧酸甲脂 在 titanium(IV) isopropylate 、 palladium diacetate 、 sodium cyanoborohydride 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 为溶剂， 生成 methyl 3-amino-6-chloro-5-[(3S)-3-ethyl-4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]piperazin-1-yl]pyrazine-2-carboxylate
  参考文献：
  名称：

  III. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl–piperazinyl–piperidine scaffold

  摘要：

  The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. Compound 16e with single-digit CXCR3 affinity, good rat PK and hERG profiles has been identified as a lead for further study. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.120

文献信息

• HETEROCYCLIC SUBSTITUTED PIPERAZINES WITH CXCR3 ANTAGONIST ACTIVITY
  申请人：Kim Seong Heon

  公开号：US20110065651A1

  公开（公告）日：2011-03-17

  The present application discloses a compound, or enantiomers, stereoisomers, rotamers, tautomers, racemates or prodrug of said compound, or pharmaceutically acceptable salts, solvates or esters of said compound, or of said prodrug, said compound having the general structure shown in Formula 1: or a pharmaceutically acceptable salt, solvate or ester thereof, wherein the various moieties are defined herein. 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.

  本申请披露了一种化合物，或该化合物的对映体、立体异构体、转轮异构体、互变异构体、外消旋体或前药，或该化合物或该前药的药学上可接受的盐、溶剂合物或酯，该化合物具有如公式1所示的一般结构，或其药学上可接受的盐、溶剂合物或酯，其中各种基团在此处定义。还披露了一种治疗趋化因子介导疾病的方法，例如，某些疾病和病症的姑息疗法、治愈疗法、预防性疗法，如炎症性疾病（非限制性例子包括银屑病），自身免疫性疾病（非限制性例子包括类风湿性关节炎、多发性硬化症），移植排斥（非限制性例子包括同种异体排斥、异种排斥），传染病（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，I型糖尿病，病毒性脑膜炎和肿瘤，使用公式1的化合物。
• WO2006/88836
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2006/91428
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2006/88837
  申请人：——

  公开号：——

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

  公开号：EP1858895B1

  公开（公告）日：2012-06-20