1,3-thiazol-5-ylmethyl N-[(2R,5R)-5-amino-1,6-diphenylhexan-2-yl]-N-methylcarbamate | 1551455-22-1

• 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: 1,3-thiazol-5-ylmethyl N-[(2R,5R)-5-amino-1,6-diphenylhexan-2-yl]-N-methylcarbamate
• CAS: 1551455-22-1
• 化学式: C₂₄H₂₉N₃O₂S
• 分子量: 423.579
• InChiKey: JAVZMVJFQHZCFO-FGZHOGPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  96.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,3-thiazol-5-ylmethyl N-[(2R,5R)-5-amino-1,6-diphenylhexan-2-yl]-N-methylcarbamate 、 N-[2-异丙基噻唑-4-甲基氨基甲酰]-L-缬氨酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 生成 thiazol-5-ylmethyl N-[(1R,4R)-1-benzyl-4-[[(2S)-2-[[(2-isopropylthiazol-4-yl)methyl-methyl-carbamoyl]amino]-3-methyl-butanoyl]amino]-5-phenyl-pentyl]-N-methyl-carbamate
  参考文献：
  名称：

  Structure–activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers, part I: Core region

  摘要：

  Ritonavir (RTV), an HIV-1 protease inhibitor (PI), is also a potent mechanism-based inhibitor of human cytochrome P450 3A (CYP3A) and has been widely prescribed as a pharmacoenhancer. As a boosting agent for marketed PIs, it reduces pill burden, and improves compliance. Removal of the hydroxyl group from RTV reduces, but does not eliminate HIV PI activity and does not affect CYP3A inhibition. Herein we report the discovery of a novel series of CYP3A inhibitors that are devoid of antiviral activity. The synthesis and evaluation of analogs with extensive modifications of the 1,4-diamine core along with the structure activity relationships with respect to anti-HIV activity, CYP3A inhibitory activity, selectivity against other CYP enzymes and the human pregnane X receptor (PXR) will be discussed. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.058
• 作为产物：
  描述：

  (2R,5R)-5-N-methyl-1,6-diphenylhexane-2,5-diamine 、 ((5-噻唑基)甲基)-(4-硝基苯基)碳酸酯 在 N,N-二异丙基乙胺 作用下， 生成 1,3-thiazol-5-ylmethyl N-[(2R,5R)-5-amino-1,6-diphenylhexan-2-yl]-N-methylcarbamate
  参考文献：
  名称：

  Structure–activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers, part I: Core region

  摘要：

  Ritonavir (RTV), an HIV-1 protease inhibitor (PI), is also a potent mechanism-based inhibitor of human cytochrome P450 3A (CYP3A) and has been widely prescribed as a pharmacoenhancer. As a boosting agent for marketed PIs, it reduces pill burden, and improves compliance. Removal of the hydroxyl group from RTV reduces, but does not eliminate HIV PI activity and does not affect CYP3A inhibition. Herein we report the discovery of a novel series of CYP3A inhibitors that are devoid of antiviral activity. The synthesis and evaluation of analogs with extensive modifications of the 1,4-diamine core along with the structure activity relationships with respect to anti-HIV activity, CYP3A inhibitory activity, selectivity against other CYP enzymes and the human pregnane X receptor (PXR) will be discussed. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.058

文献信息

• MODULATORS OF PHARMACOKINETIC PROPERTIES OF THERAPEUTICS
  申请人：Gilead Sciences, Inc.

  公开号：US20140017199A1

  公开（公告）日：2014-01-16

  The present application provides for a compound of Formula IV, or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.
• Structure–activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers, part I: Core region
  作者：Hongtao Liu、Lianhong Xu、Hon Hui、Randy Vivian、Christian Callebaut、Bernard P. Murray、Allen Hong、Melody S. Lee、Luong K. Tsai、Jennifer K. Chau、Kirsten M. Stray、Carina Cannizzaro、You-Chul Choi、Gerry R. Rhodes、Manoj C. Desai

  DOI：10.1016/j.bmcl.2013.12.058

  日期：2014.2

  Ritonavir (RTV), an HIV-1 protease inhibitor (PI), is also a potent mechanism-based inhibitor of human cytochrome P450 3A (CYP3A) and has been widely prescribed as a pharmacoenhancer. As a boosting agent for marketed PIs, it reduces pill burden, and improves compliance. Removal of the hydroxyl group from RTV reduces, but does not eliminate HIV PI activity and does not affect CYP3A inhibition. Herein we report the discovery of a novel series of CYP3A inhibitors that are devoid of antiviral activity. The synthesis and evaluation of analogs with extensive modifications of the 1,4-diamine core along with the structure activity relationships with respect to anti-HIV activity, CYP3A inhibitory activity, selectivity against other CYP enzymes and the human pregnane X receptor (PXR) will be discussed. (C) 2013 Elsevier Ltd. All rights reserved.