Carbonic acid (1R,2S)-2-tert-butoxycarbonylamino-1-{[isobutyl-(4-nitro-benzenesulfonyl)-amino]-methyl}-3-phenyl-propyl ester 4-nitro-phenyl ester | 229495-94-7

• 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: Carbonic acid (1R,2S)-2-tert-butoxycarbonylamino-1-{[isobutyl-(4-nitro-benzenesulfonyl)-amino]-methyl}-3-phenyl-propyl ester 4-nitro-phenyl ester
• 英文别名: [(2R,3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-1-[2-methylpropyl-(4-nitrophenyl)sulfonylamino]-4-phenylbutan-2-yl] (4-nitrophenyl) carbonate
• CAS: 229495-94-7
• 化学式: C₃₂H₃₈N₄O₁₁S
• 分子量: 686.74
• InChiKey: JTVJSHZWATZNQA-URLMMPGGSA-N

物化性质

• 密度：
  1.313±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  48
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  211
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  Carbonic acid (1R,2S)-2-tert-butoxycarbonylamino-1-{[isobutyl-(4-nitro-benzenesulfonyl)-amino]-methyl}-3-phenyl-propyl ester 4-nitro-phenyl ester 在 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 48.5h， 生成
  参考文献：
  名称：

  Novel prodrug approach to amprenavir-based HIV-1 protease inhibitors via O→N acyloxy migration of P1 moiety

  摘要：

  We have developed a new approach to prodrugs, which utilizes a pH-induced intramolecular O --> N migration of an acyloxy group in carbonate moiety to a free amino moiety at neutral pH. This method is exemplified by facile rearrangement of highly water-soluble prodrug 3 to carbarnate 4, a close analogue of HIV-1 protease inhibitor Amprenavir. The O --> N acyloxy migration is unprecedented in the context of prodrugs and it enables a high atom economy due to recycling of the 'pro' moiety. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00463-3
• 作为产物：
  描述：

  二(对硝基苯)碳酸酯 、 [(1S,2R)-1-苄基-2-羟基-3-[异丁基[(4-硝基苯基)磺酰]氨基]丙基]氨基甲酸叔丁酯 在 lithium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以80%的产率得到Carbonic acid (1R,2S)-2-tert-butoxycarbonylamino-1-{[isobutyl-(4-nitro-benzenesulfonyl)-amino]-methyl}-3-phenyl-propyl ester 4-nitro-phenyl ester
  参考文献：
  名称：

  Novel prodrug approach to amprenavir-based HIV-1 protease inhibitors via O→N acyloxy migration of P1 moiety

  摘要：

  We have developed a new approach to prodrugs, which utilizes a pH-induced intramolecular O --> N migration of an acyloxy group in carbonate moiety to a free amino moiety at neutral pH. This method is exemplified by facile rearrangement of highly water-soluble prodrug 3 to carbarnate 4, a close analogue of HIV-1 protease inhibitor Amprenavir. The O --> N acyloxy migration is unprecedented in the context of prodrugs and it enables a high atom economy due to recycling of the 'pro' moiety. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00463-3

文献信息

• SULPHONAMIDE DERIVATIVES AS PRODRUGS OF ASPARTYL PROTEASE INHIBITORS
  申请人：Tung Roger Dennis

  公开号：US20100124543A1

  公开（公告）日：2010-05-20

  The present invention relates to prodrugs of a class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of prodrugs of HIV aspartyl protease inhibitors characterized by favorable aqueous solubility, high oral bioavailability and facile in vivo generation of the active ingredient. This invention also relates to pharmaceutical compositions comprising these prodrugs. The prodrugs and pharmaceutical compositions of this invention are particularly well suited for decreasing the pill burden and increasing patient compliance. This invention also relates to methods of treating mammals with these prodrugs and pharmaceutical compositions.
• US7592368B2
  申请人：——

  公开号：US7592368B2

  公开（公告）日：2009-09-22
• Novel prodrug approach to amprenavir-based HIV-1 protease inhibitors via O→N acyloxy migration of P1 moiety
  作者：Wieslaw M Kazmierski、Patricia Bevans、Eric Furfine、Andrew Spaltenstein、Hanbiao Yang

  DOI：10.1016/s0960-894x(03)00463-3

  日期：2003.8

  We have developed a new approach to prodrugs, which utilizes a pH-induced intramolecular O --> N migration of an acyloxy group in carbonate moiety to a free amino moiety at neutral pH. This method is exemplified by facile rearrangement of highly water-soluble prodrug 3 to carbarnate 4, a close analogue of HIV-1 protease inhibitor Amprenavir. The O --> N acyloxy migration is unprecedented in the context of prodrugs and it enables a high atom economy due to recycling of the 'pro' moiety. (C) 2003 Elsevier Ltd. All rights reserved.