Tert-butyl (1R,3R,4S)-4-((S)-2-benzyloxycarbonylamino-4-(methylthio)butanamido)-3-(tert-butylsulfonylmethyl)cyclohexylcarbamate | 848002-01-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Tert-butyl (1R,3R,4S)-4-((S)-2-benzyloxycarbonylamino-4-(methylthio)butanamido)-3-(tert-butylsulfonylmethyl)cyclohexylcarbamate
• 英文别名: benzyl N-[(2S)-1-[[(1S,2R,4R)-2-(tert-butylsulfonylmethyl)-4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexyl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]carbamate
• CAS: 848002-01-7
• 化学式: C₂₉H₄₇N₃O₇S₂
• 分子量: 613.84
• InChiKey: WBKPYSQNWFRTRS-KIHHCIJBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  41
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  174
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Tert-butyl (1R,3R,4S)-4-((S)-2-benzyloxycarbonylamino-4-(methylthio)butanamido)-3-(tert-butylsulfonylmethyl)cyclohexylcarbamate 在 N-甲基吗啉 、 palladium on activated charcoal 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 caesium carbonate 、 三氟乙酸 、 碘甲烷 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-((S)-1-((1S,2R,4R)-4-amino-2-((tert-butylsulfonyl)methyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Alkylsulfone-containing trisubstituted cyclohexanes as potent and bioavailable chemokine receptor 2 (CCR2) antagonists

  摘要：

  We describe novel alkylsulfones as potent CCR2 antagonists with reduced hERG channel activity and improved pharmacokinetics over our previously described antagonists. Several of these new alkylsulfones have a profile that includes functional antagonism of CCR2, in vitro microsomal stability, and oral bioavailability. With this improved profile, we demonstrate that two of these antagonists, 2 and 12, are orally efficacious in an animal model of inflammatory recruitment. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.013
• 作为产物：
  描述：

  benzyl (1S,2R,4R)-4-(tert-butoxycarbonylamino)-2-(hydroxymethyl)cyclohexylcarbamate 在 N-甲基吗啉 、 palladium on activated charcoal 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 臭氧 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 生成 Tert-butyl (1R,3R,4S)-4-((S)-2-benzyloxycarbonylamino-4-(methylthio)butanamido)-3-(tert-butylsulfonylmethyl)cyclohexylcarbamate
  参考文献：
  名称：

  Alkylsulfone-containing trisubstituted cyclohexanes as potent and bioavailable chemokine receptor 2 (CCR2) antagonists

  摘要：

  We describe novel alkylsulfones as potent CCR2 antagonists with reduced hERG channel activity and improved pharmacokinetics over our previously described antagonists. Several of these new alkylsulfones have a profile that includes functional antagonism of CCR2, in vitro microsomal stability, and oral bioavailability. With this improved profile, we demonstrate that two of these antagonists, 2 and 12, are orally efficacious in an animal model of inflammatory recruitment. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.013

文献信息

• Cyclic derivatives as modulators of chemokine receptor activity
  申请人：Carter H. Percy

  公开号：US20050054627A1

  公开（公告）日：2005-03-10

  The present application describes modulators of MCP-1 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the treatment of rheumatoid arthritis, multiple sclerosis, atherosclerosis and asthma.

  本申请描述了MCP-1的调节剂，其化学式为(I)或其药学上可接受的盐形式，适用于类风湿性关节炎、多发性硬化症、动脉粥样硬化和哮喘的治疗。
• CYCLIC DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：Carter Percy H.

  公开号：US20090124668A1

  公开（公告）日：2009-05-14

  The present application describes modulators of MCP-1 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the treatment of rheumatoid arthritis, multiple sclerosis, atherosclerosis and asthma.

  本申请描述了 MCP-1 的调节剂，其化学式为 (I) 或其药学上可接受的盐形式，适用于治疗类风湿性关节炎、多发性硬化症、动脉粥样硬化和哮喘。
• Alkylsulfone-containing trisubstituted cyclohexanes as potent and bioavailable chemokine receptor 2 (CCR2) antagonists
  作者：Robert J. Cherney、Ruowei Mo、Michael G. Yang、Zili Xiao、Qihong Zhao、Sandhya Mandlekar、Mary Ellen Cvijic、Israel F. Charo、Joel C. Barrish、Carl P. Decicco、Percy H. Carter

  DOI：10.1016/j.bmcl.2014.02.013

  日期：2014.4

  We describe novel alkylsulfones as potent CCR2 antagonists with reduced hERG channel activity and improved pharmacokinetics over our previously described antagonists. Several of these new alkylsulfones have a profile that includes functional antagonism of CCR2, in vitro microsomal stability, and oral bioavailability. With this improved profile, we demonstrate that two of these antagonists, 2 and 12, are orally efficacious in an animal model of inflammatory recruitment. (C) 2014 Elsevier Ltd. All rights reserved.