5-chloro-6-[(3S)-4-[1-[(4-chloro-2-fluorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]pyridine-3-carbonitrile | 906559-53-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 5-chloro-6-[(3S)-4-[1-[(4-chloro-2-fluorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]pyridine-3-carbonitrile
• CAS: 906559-53-3
• 化学式: C₂₄H₂₈Cl₂FN₅
• 分子量: 476.424
• InChiKey: JBCZCRDJYWCRCV-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-chloro-6-[(3S)-4-[1-[(4-chloro-2-fluorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]pyridine-3-carbonitrile 在 三甲基铝 、 肼 作用下， 以 正庚烷 为溶剂， 反应 60.17h， 以56%的产率得到N'-amino-5-chloro-6-[(3S)-4-[1-[(4-chloro-2-fluorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]pyridine-3-carboximidamide
  参考文献：
  名称：

  WO2006/88840

  摘要：

  公开号：
• 作为产物：
  描述：

  1-(4-chloro-2-fluoro-benzyl)-piperidin-4-one 、 5-chloro-6-[(3S)-3-ethylpiperazin-1-yl]pyridine-3-carbonitrile 在 三乙酰氧基硼氢化钠 、 水 、 碳酸氢钠 作用下， 以 1,2-二氯乙烷 、 二氯甲烷 为溶剂， 反应 48.5h， 以62%的产率得到5-chloro-6-[(3S)-4-[1-[(4-chloro-2-fluorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]pyridine-3-carbonitrile
  参考文献：
  名称：

  WO2006/88840

  摘要：

  公开号：

文献信息

• Pyridyl and phenyl substituted piperazine-piperidines with CXCR3 antagonist activity
  申请人：McGuinness F. Brian

  公开号：US20070021611A1

  公开（公告）日：2007-01-25

  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: and the pharmaceutically acceptable salts, solvates and 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，或该化合物的药学上可接受的盐、溶剂化合物或酯，或该前药的药学上可接受的盐、溶剂化合物或酯，该化合物具有如公式1所示的一般结构，以及其药学上可接受的盐、溶剂化合物和酯。还公开了一种使用公式1的化合物治疗趋化因子介导的疾病的方法，例如，缓解治疗、治愈治疗、预防性治疗某些疾病和情况，如炎症性疾病（非限定性例子包括牛皮癣），自身免疫性疾病（非限定性例子包括类风湿性关节炎、多发性硬化症），移植排斥反应（非限定性例子包括同种异体移植排斥反应、异种移植排斥反应），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。
• NOVEL HETEROCYCLIC SUBSTITUTED PYRIDINE OR PHENYL COMPOUNDS WITH CXCR3 ANTAGONIST ACTIVITY
  申请人：Anilkumar Gopinadhan N.

  公开号：US20080292589A1

  公开（公告）日：2008-11-27

  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. 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, zenograft 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其对映体、立体异构体、转位异构体、互变异构体、外消旋体或前药，或者该化合物的药学上可接受的盐、溶剂化物或酯，或者该前药的药学上可接受的盐、溶剂化物或酯，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、溶剂化物或酯。同时，本申请还披露了一种使用公式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、预防性治疗某些疾病和情况，例如炎症性疾病（非限定性例子包括牛皮癣）、自身免疫性疾病（非限定性例子包括类风湿性关节炎、多发性硬化）、移植排斥（非限定性例子包括同种异体排斥、异种异体排斥）、传染病（例如结核性麻风）、固定药物性皮疹、皮肤迟发型超敏反应、眼科炎症、I型糖尿病、病毒性脑膜炎和肿瘤的方法。
• WO2006/88919
  申请人：——

  公开号：——

  公开（公告）日：——
• IV. Discovery of CXCR3 antagonists substituted with heterocycles as amide surrogates: Improved PK, hERG and metabolic profiles
  作者：Anilkumar G. Nair、Michael K.C. Wong、Youheng Shu、Yueheng Jiang、Chung-Her Jenh、Seong Heon Kim、De-Yi Yang、Qingbei Zeng、Yuefei Shao、Lisa Guise Zawacki、Jingqi Duo、Brian F. McGuinness、Carolyn DiIanni Carroll、Doug W. Hobbs、Neng-Yang Shih、Stuart B. Rosenblum、Joseph A. Kozlowski

  DOI：10.1016/j.bmcl.2014.01.009

  日期：2014.2

  The structure-human CXCR3 binding affinity relationship of a series of pyridyl/pyrazinyl-piperazinyl-piperidine derivatives were explored with a focus to improve PK, hERG and metabolic profiles. Several small heterocycles were identified as amide surrogates, which minimized many potential metabolite issues. During the course of SAR development, we have observed the additive effect of desirable functional groups to improve hERG and PK profiles which lead to the discovery of many clinically developable CXCR3 antagonists with excellent overall profile. (C) 2014 Elsevier Ltd. All rights reserved.
• PYRIDYL AND PHENYL SUBSTITUTED PIPERAZINE-PIPERIDINES WITH CXCR3 ANTAGONIST ACTIVITY
  申请人：Schering Corporation

  公开号：EP1856097B1

  公开（公告）日：2012-07-11