1-(4-Biphenylyl)-5(S)-2,5-di[(tert-butoxycarbonyl)amino]-4(S)-hydroxy-6-phenyl-2-azahexane | 191594-83-9

• 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-(4-Biphenylyl)-5(S)-2,5-di[(tert-butoxycarbonyl)amino]-4(S)-hydroxy-6-phenyl-2-azahexane
• 英文别名: 1-[2(S)-hydroxy-3(S)-(tert-butoxycarbonylamino)-4-phenylbutyl]-1-[4-biphenylylmethyl]-2-[tert-butoxycarbonyl)hydrazine；tert-butyl N-[[(2S,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-phenylbutyl]-[(4-phenylphenyl)methyl]amino]carbamate
• CAS: 191594-83-9
• 化学式: C₃₃H₄₃N₃O₅
• 分子量: 561.722
• InChiKey: CKNJNYTVYJDCEP-VMPREFPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  41
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  100
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(4-Biphenylyl)-5(S)-2,5-di[(tert-butoxycarbonyl)amino]-4(S)-hydroxy-6-phenyl-2-azahexane 在 盐酸 、 O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.33h， 生成 CGP 75355
  参考文献：
  名称：

  New Aza-Dipeptide Analogues as Potent and Orally Absorbed HIV-1 Protease Inhibitors:  Candidates for Clinical Development

  摘要：

  On the basis of previously described X-ray studies of an enzyme/aza-dipeptide complex,(8) azadipeptide analogues carrying N-(bis-aryl-methyl) substituents on the (hydroxethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally (12) ororthogonally (13) protected dipeptide isosteres, symmetrically and asymmetrically acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxethyl)hydrazine dipeptide isostere with the L-tert-leucine derivative 29 increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives. The bis(L-tert-leucine) derivatives CGP 75355, CGP 73547, CGP 75136, and CGP 75176 combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clinical candidates.

  DOI：

  10.1021/jm970873c
• 作为产物：
  描述：

  N-Boc-L-苯丙氨醛 在 镍 Sodium tetraborate decahydrate 、 benzylcinchoninium chloride 、 氢气 、 二异丁基氢化铝 、 sodium cyanoborohydride 、 对甲苯磺酸 、 溶剂黄146 、 7-甲基-1,5,7-三氮杂二环[4.4.0]癸-5-烯 作用下， 以 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 25.0 ℃ 、100.0 kPa 条件下， 反应 2.5h， 生成 1-(4-Biphenylyl)-5(S)-2,5-di[(tert-butoxycarbonyl)amino]-4(S)-hydroxy-6-phenyl-2-azahexane
  参考文献：
  名称：

  A concise synthesis of aza-dipeptide isosteres

  摘要：

  Aza-dipeptide isosteres as potent HIV-protease inhibitors containing a (hydroxyethyl)-hydrazine moiety are synthesised in >98% diastereomeric and enantiomeric purity starting from (L)-phenylalanine aldehyde. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)00897-1

文献信息

• Intermediates for the preparation of peptide analogues
  申请人：Novartis Finance Corporation

  公开号：US05912352A1

  公开（公告）日：1999-06-15

  The invention relates to a novel process for the preparation of compounds of formula I ##STR1## wherein R.sub.1 is hydrogen or a suitable amino-protecting group, R.sub.2 is unsubstituted or substituted alkyl, R.sub.3 is hydrogen, aryl, heterocyclyl, unsubstituted or substituted alkyl or unsubstituted or substituted cycloalkyl, R.sub.4, independently of R.sub.1, is hydrogen or a suitable amino-protecting group and m is a number from 1 to 7; and wherein further suitable protecting groups for functional groups may be present; which compounds are antivirally active or can be used as starting materials for pharmaceutically active, especially antiviral compounds. The precursor is an oxo compound, which is in turn prepared by hydrogenation with a suitable complex hydride or with hydrogen in the presence of a suitable catalyst and acyl migration starting from a hydrazone, which is in turn preferably prepared from a nitrile via an imino compound by means of hydrogenation and reaction with a hydrazine derivative, which is prepared from an aldehyde by reaction with a reactive derivative of a carboxylic acid in the presence of a cyanide salt; and the novel intermediates required therefor.

  这项发明涉及一种新型制备化合物的方法，其化学式为I，其中R.sub.1是氢或适当的氨基保护基，R.sub.2是未取代或取代的烷基，R.sub.3是氢、芳基、杂环烷基、未取代或取代的烷基或未取代或取代的环烷基，R.sub.4独立于R.sub.1，是氢或适当的氨基保护基，m为1到7的数字；进一步适用于功能基的保护基可能存在；这些化合物具有抗病毒活性，或可用作制药活性的起始物，特别是抗病毒化合物。该前体是一种酮化合物，该酮化合物又通过与适当的复合氢化物或催化剂存在下的氢化以及从酰肼起始的酰迁移制备而来，而酰肼则最好是通过氰化物盐存在下的醛与羧酸的反应衍生的重活性衍生物制备而来，而羧酸则是通过从腈经由亚胺化合物的氢化和与联氨衍生物反应制备而来；以及所需的新型中间体。
• Methods of treating alzheimer's disease
  申请人：Schostarez Heinrich

  公开号：US20050130941A1

  公开（公告）日：2005-06-16

  Disclosed are methods for treating Alzheimer's disease, and other diseases, and/or inhibiting beta-secretase enzyme, and/or inhibiting deposition of A beta peptide in a mammal, by use of hydrazine compounds of formula (I) wherein the variables R 1 -R 9 are defined herein.

  本发明涉及使用式(I)中变量R1-R9所定义的肼化合物治疗阿尔茨海默病和其他疾病，抑制β-分泌酶酶活性，抑制A beta肽在哺乳动物体内的沉积。
• Antiretroviral hydrazine derivatives
  申请人：Novartis Corporation

  公开号：US05753652A1

  公开（公告）日：1998-05-19

  The invention relates to compounds of formula ##STR1## and salts, pharmaceutical compositions, intermediates and processes of preparation thereof.

  本发明涉及式子##STR1##的化合物及其盐、药物组合物、中间体和制备方法。
• METHODS OF TREATING ALZHEIMER'S DISEASE
  申请人：Elan Pharmaceuticals, Inc.

  公开号：EP1392315A1

  公开（公告）日：2004-03-03
• [EN] METHODS OF TREATING ALZHEIMER'S DISEASE<br/>[FR] PROCEDES DE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：ELAN PHARM INC

  公开号：WO2002100410A1

  公开（公告）日：2002-12-19

  Disclosed are methods for treating Alzheimer's disease, and other diseases, and/or inhibiting beta-secretase enzyme, and/or inhibiting deposition of A beta peptide in a mammal, by use of hydrazine compounds of formula (I) wherein the variables R1-R9 are defined herein.