N-(2-chloro-3-fluorophenyl)-N'-{4-chloro-2-hydroxy-3-[(3S)-3-pyrrolidinylsulfonyl]phenyl}urea | 954127-22-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-chloro-3-fluorophenyl)-N'-{4-chloro-2-hydroxy-3-[(3S)-3-pyrrolidinylsulfonyl]phenyl}urea
• 英文别名: 1-(2-chloro-3-fluorophenyl)-3-[4-chloro-2-hydroxy-3-[(3S)-pyrrolidin-3-yl]sulfonylphenyl]urea
• CAS: 954127-22-1
• 化学式: C₁₇H₁₆Cl₂FN₃O₄S
• 分子量: 448.302
• InChiKey: CRHQLGHPEWNKIT-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2-chloro-3-fluorophenyl)-N'-{4-chloro-2-hydroxy-3-[(3S)-3-pyrrolidinylsulfonyl]phenyl}urea 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.08h， 生成 N-(2-chloro-3-fluorophenyl)-N'-(4-chloro-2-hydroxy-3-{[(3S)-1-methyl-3-pyrrolidinyl]sulfonyl}phenyl)urea trifluoroacetic acid salt
  参考文献：
  名称：

  Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders

  摘要：

  Structure-activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key compound 22 showed efficacy in a cuprizone-induced demyelination model with twice daily oral administration, thereby supporting CXCR2 to be a potential therapeutic target for the treatment of demyelinating diseases such as multiple sclerosis.

  DOI：

  10.1021/acsmedchemlett.5b00489
• 作为产物：
  描述：

  2-(tert-butyl)-6-chlorobenzo[d]oxazole-7-thiol 在 硫酸 、 caesium carbonate 、 间氯过氧苯甲酸 、 三氟乙酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 N-(2-chloro-3-fluorophenyl)-N'-{4-chloro-2-hydroxy-3-[(3S)-3-pyrrolidinylsulfonyl]phenyl}urea
  参考文献：
  名称：

  Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders

  摘要：

  Structure-activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key compound 22 showed efficacy in a cuprizone-induced demyelination model with twice daily oral administration, thereby supporting CXCR2 to be a potential therapeutic target for the treatment of demyelinating diseases such as multiple sclerosis.

  DOI：

  10.1021/acsmedchemlett.5b00489

文献信息

• IL-8 Receptor Antagonists
  申请人：BUSCH-PETERSEN Jakob

  公开号：US20070249672A1

  公开（公告）日：2007-10-25

  This invention relates to novel compounds and compositions thereof, useful in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).

  该发明涉及新颖的化合物及其组合物，可用于治疗由趋化因子白细胞介素-8（IL-8）介导的疾病状态。
• IL-8 RECEPTOR ANTAGONISTS
  申请人：Busch-Petersen Jakob

  公开号：US20110059937A1

  公开（公告）日：2011-03-10

  This invention relates to novel compounds and compositions thereof, useful in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).

  本发明涉及新型化合物及其组合物，用于治疗由趋化因子白细胞介素-8（IL-8）介导的疾病状态。
• US7893089B2
  申请人：——

  公开号：US7893089B2

  公开（公告）日：2011-02-22
• [EN] IL-8 RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RÉCEPTEUR DE L'INTERLEUKINE 8
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2007124424A2

  公开（公告）日：2007-11-01

  [EN] This invention relates to novel compounds and compositions thereof, useful in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).
  [FR] L'invention concerne de nouveaux composés et des compositions de ceux-ci, utilisés dans le traitement d'états pathologiques médiés par la chimiokine Interleukine-8 (IL-8).
• Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders
  作者：Heng Xu、Hongfu Lu、Zhongmiao Xu、Linbo Luan、Chengyong Li、Yan Xu、Kelly Dong、Jinqiang Zhang、Xiong Li、Yvonne Li、Gentao Liu、Sophie Gong、Yong-Gang Zhao、Ailian Liu、Yueting Zhang、Wei Zhang、Xin Cai、Jia-Ning Xiang、John D. Elliott、Xichen Lin

  DOI：10.1021/acsmedchemlett.5b00489

  日期：2016.4.14

  Structure-activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key compound 22 showed efficacy in a cuprizone-induced demyelination model with twice daily oral administration, thereby supporting CXCR2 to be a potential therapeutic target for the treatment of demyelinating diseases such as multiple sclerosis.