(S)-(1-(4-(苄氧基)苯基)-4-氯-3-氧代丁烷-2-基)氨基甲酸叔丁酯 | 152438-62-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (S)-(1-(4-(苄氧基)苯基)-4-氯-3-氧代丁烷-2-基)氨基甲酸叔丁酯
• 英文名称: (S)-N-[3-Chloro-2-oxo-1-[[4-(phenylmethoxy)phenyl]methyl]propyl]carbamic acid 1,1-dimethylethyl ester
• 英文别名: (S)-tert-butyl (1-(4-(benzyloxy)phenyl)-4-chloro-3-oxobutan-2-yl)carbamate；Boc-Tyr(Bzl)-CH2Cl；tert-butyl N-[(2S)-4-chloro-3-oxo-1-(4-phenylmethoxyphenyl)butan-2-yl]carbamate
• CAS: 152438-62-5
• 化学式: C₂₂H₂₆ClNO₄
• 分子量: 403.906
• InChiKey: ZQCWGEVCMARRSG-IBGZPJMESA-N

物化性质

• 沸点：
  549.1±50.0 °C(Predicted)
• 密度：
  1.175±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 储存条件：
  存储条件为2-8°C，并需保存在惰性气体中。

反应信息

• 作为反应物：
  描述：

  (S)-(1-(4-(苄氧基)苯基)-4-氯-3-氧代丁烷-2-基)氨基甲酸叔丁酯 在 palladium on activated charcoal 氢氧化钾 、 sodium tetrahydroborate 、 偶氮二甲酸二叔丁酯 、 氢气 、 N,N-二异丙基乙胺 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 异丙醇 、 乙腈 为溶剂， 生成 (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-[4-(2-aminoethoxy)benzyl]-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxypropylcarbamate
  参考文献：
  名称：

  Novel P1 chain-extended HIV protease inhibitors possessing potent anti-HIV activity and remarkable inverse antiviral resistance profiles

  摘要：

  A novel series of tyro si ne-derived HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and two protease inhibitor-resistant viruses. All of the compounds had wild-type antiviral activities that were similar to or greater than several currently marketed HIV protease inhibitors. In addition, a number of compounds in this series were more potent against the drug-resistant mutant viruses than they were against wild-type virus. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.129
• 作为产物：
  描述：

  Boc-O-苄基-L-酪氨酸 在 N-甲基吗啉 、 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 为溶剂， 生成 (S)-(1-(4-(苄氧基)苯基)-4-氯-3-氧代丁烷-2-基)氨基甲酸叔丁酯
  参考文献：
  名称：

  氨基二醇HIV蛋白酶抑制剂。P1 / P1'化合物的合成与构效关系：亲脂性和细胞毒性之间的关系。

  摘要：

  为了减少1的细胞毒性，合成了一系列基于P1'结构修饰的先导化合物1的HIV蛋白酶的新型氨基二醇抑制剂。我们已经观察到该系列抑制剂的亲脂性和细胞毒性之间存在高度相关性。 。发现在P1'苯基基团对位1处的适当取代导致鉴定出等价的（对酶和细胞培养均如此）化合物（10l，10m，10n和15c），这些化合物具有明显降低的细胞毒性。

  DOI：

  10.1021/jm950717a

文献信息

• Development of Active Center-Directed Plasmin and Plasma Kallikrein Inhibitors and Studies on the Structure-Inhibitory Activity Relationship.
  作者：Naoki TENO、Keiko WANAKA、Yoshio OKADA、Hiroaki TAGUCHI、Utako OKAMOTO、Akiko HIJIKATA-OKUNOMIYA、Shosuke OKAMOTO

  DOI：10.1248/cpb.41.1079

  日期：——

  The molecule of trans-4-aminomethylcyclohexanecarbonylphenylalanine 4-carboxymethylanilide (8), which is a potent and selective inhibitor of plasma kallikrein, can be devided into three parts (P1, P1' and P2'), each of which contains one of the rings. In order to study the role of each part in the manifestation of potent and selective inhibitory activity and the relationship between the structure and inhibitory activities toward plasmin, plasma kallikrein, urokinase and thrombin, each part was substituted with various other moieties to give many kinds of analogs and their inhibitory activities against the above enzymes were examined. Among them, trans-4-aminomethylcyclohexanecarbonyl-O-2-bromobenzyloxycarbonyltyrosine 4-acetylanilide (12) inhibited plasmin and plasma kallikrein with IC50 values of 2.3×10-7 M and 3.7×10-7 M, and Ki values of 1.2×10-7 M and 1.3×10-7 M, respectively.

  翻译结果： 分子trans-4-氨基甲基环己烷羰基苯丙氨酸4-羧甲基苯甲酰胺（8）是一种有效的选择性血浆激肽释放酶抑制剂，可以分为三个部分（P1，P1'和P2'），每个部分包含一个环。为了研究每个部分在表现强效选择性抑制活性中的作用以及结构与对纤溶酶、血浆激肽释放酶、尿激酶和凝血酶抑制活性之间的关系，每个部分被不同基团取代，生成多种类似物，并检测它们对上述酶的抑制活性。其中，trans-4-氨基甲基环己烷羰基-O-2-溴苄氧羰基酪氨酸4-乙酰苯甲酰胺（12）对纤溶酶和血浆激肽释放酶的IC50值分别为2.3×10-7 M和3.7×10-7 M，Ki值分别为1.2×10-7 M和1.3×10-7 M。
• A practical method for the preparation of α′-chloroketones of N-carbamate protected-α-aminoacids
  作者：Ping Chen、Peter T.W. Cheng、Steven H. Spergel、Robert Zahler、Xuebao Wang、John Thottathil、Joel C. Barrish、Richard P. Polniaszek

  DOI：10.1016/s0040-4039(97)00605-9

  日期：1997.5

  A practical method for the preparation of α-N-BOC-epoxides from protected amino acid esters based on the Kowalski homologation reaction is described. This procedure can be readily performed on a large scale without the use of hazardous reagents and has allowed preparation of epoxides 3 in multi-kilogram quantities.

  描述了一种基于Kowalski同源反应从受保护的氨基酸酯制备α-N-BOC-环氧化合物的实用方法。该方法可以容易地大规模进行而无需使用危险试剂，并且可以制备多千克量的环氧化物3。
• Cellular accumulation of phosphonate analogs of hiv protease inhibitor compounds
  申请人：Arimilli N. Murty

  公开号：US20070010489A1

  公开（公告）日：2007-01-11

  Phosphonate substituted compounds with HIV protease inhibitory properties having use as therapeutics and for other industrial purposes are disclosed. The compositions inhibit 5 HIV protease activity and/or are useful therapeutically for the treatment of AIDS and other antiviral infections, as well as in assays for the detection of HIV protease.

  本发明揭示了具有HIV蛋白酶抑制剂性质的膦酸酯取代化合物，其具有作为治疗剂和其他工业用途的用途。该组合物抑制5型HIV蛋白酶活性和/或在治疗艾滋病和其他抗病毒感染方面具有治疗作用，以及在检测HIV蛋白酶方面的检测中有用。
• Method and compositions for identifying anti-hiv therapeutic compounds
  申请人：Birkus Gabriel

  公开号：US20070190523A1

  公开（公告）日：2007-08-16

  The invention relates to methods and compositions for identifying compounds having therapeutic activity against human immunodeficiency virus (HIV).

  本发明涉及用于鉴定具有治疗人类免疫缺陷病毒（HIV）活性的化合物的方法和组合物。
• Synthesis and pharmacokinetic profile of highly deuterated brecanavir analogs
  作者：Emile J. Velthuisen、Todd M. Baughman、Brian A. Johns、David P. Temelkoff、Jason G. Weatherhead

  DOI：10.1016/j.ejmech.2013.02.001

  日期：2013.5

  Several highly deuterated analogs of the HIV-1 protease inhibitor brecanavir have been prepared to study the effect of deuterium upon metabolic stability. The sites for deuterium incorporation were initially chosen to maximize the potential for a kinetic isotope effect; locations where C-H bond breaking is the rate limiting step. The analogs have been profiled in both in vitro and in vivo pharmacokinetic studies and the result will be described herein. (C) 2013 Elsevier Masson SAS. All rights reserved.