(2R,3S)-3-Cbz-amino-2-hydroxy-4-phenyl-1-benzylaminobutane | 143224-83-3

• 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: (2R,3S)-3-Cbz-amino-2-hydroxy-4-phenyl-1-benzylaminobutane
• 英文别名: benzyl N-[(2S,3R)-4-(benzylamino)-3-hydroxy-1-phenylbutan-2-yl]carbamate
• CAS: 143224-83-3
• 化学式: C₂₅H₂₈N₂O₃
• 分子量: 404.509
• InChiKey: XTHSULXWZOZNLU-BJKOFHAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R,3S)-3-Cbz-amino-2-hydroxy-4-phenyl-1-benzylaminobutane 在 N-甲基吗啉 、 10% palladium on activated charcoal 、 甲酸铵 、 碳酸氢钠 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 甲醇 、 水 、 1,2-二氯乙烷 、 乙腈 为溶剂， 生成 N-[(2S,3R)-4-[(4-acetamidophenyl)sulfonyl-benzylamino]-3-hydroxy-1-phenylbutan-2-yl]-3-(1H-indol-3-yl)propanamide
  参考文献：
  名称：

  掺入苯并杂环作为HIV-1蛋白酶抑制剂的新型伪肽的设计，生物学评估和SAR。

  摘要：

  合成了一系列基于（羟乙基氨基）-磺酰胺类异构体的新型HIV-1蛋白酶抑制剂，该抑制剂结合了取代的苯基和带有丰富氢键受体作为P 2配体的苯并杂环衍生物。延长将苄环与羰基连接的链导致部分结合亲和力损失。在P 1- P 2键的-CH 2-侧链中引入适当大小的小烷基取代基可提高抑菌效力，在本研究中，异丙基是最佳的侧链。用苯基取代基取代P 1 '基上的异丁基取代基降低了抑制能力。最有效的抑制剂之一，化合物23示出了具有集成电路的高亲和性HIV-1蛋白酶50的5的n值米，也显示出良好的抗SIV活性（EC 50  = 0.8μ米具有低毒性（TC）50  > 100μ米）。抑制剂23与HIV-1蛋白酶活性位点的灵活对接使与蛋白酶的相互作用合理化。

  DOI：

  10.1111/j.1747-0285.2010.00995.x
• 作为产物：
  描述：

  Z-Phe-O-COO-isoBu 在 盐酸 、 氢氧化钾 、 sodium tetrahydroborate 、 lithium perchlorate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 乙醇 、 水 、 乙腈 为溶剂， 反应 27.25h， 生成 (2R,3S)-3-Cbz-amino-2-hydroxy-4-phenyl-1-benzylaminobutane
  参考文献：
  名称：

  Amino Diol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR

  摘要：

  A series of HIV protease inhibitors containing a novel C-2 symmetrical ''aminodiol'' core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (K-i = 100 nM; ED(50) (HIV-1) = 80 nM) containing P-1/P-1', benzyl and P-2/P-2' Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).

  DOI：

  10.1021/jm00038a005

文献信息

• Succinoylamino hydroxyethylamino sulfonyl urea derivatives useful as retroviral protease inhibitors
  申请人：G.D. Searle & Co.

  公开号：US06337398B1

  公开（公告）日：2002-01-08

  Succinoylamino hydroxyethylamino sulfonyl urea derivatives of the formula: wherein the substituents are as defined in the specification, are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.

  丁酰氨基羟基乙氨基磺酰脲衍生物的公式如下： 其中，取代基的定义如说明书所述，这些衍生物作为逆转录病毒蛋白酶抑制剂是有效的，尤其是作为HIV蛋白酶的抑制剂。
• [EN] COMPOUNDS FOR LYSOSOMAL MODULATION AND METHODS OF USE<br/>[FR] COMPOSÉS POUR MODULATION LYSOSOMALE ET PROCÉDÉS D'UTILISATION
  申请人：UNIV CONNECTICUT

  公开号：WO2009129532A1

  公开（公告）日：2009-10-22

  Compounds useful for promoting lysosomal processes and thereby ameliorating the disruption of cellular and functional integrity induced by Aβ and other protein and glycoconjugate species are provided. Methods for the treatment of neurodegenerative diseases that involve protein accumulation and aggregation in the brain, such as Alzheimer's, Parkinson's and Huntington's Disease, are also provided.

  提供了用于促进溶酶体过程并从而改善由Aβ和其他蛋白质和糖蛋白物种引起的细胞和功能完整性破坏的化合物。还提供了用于治疗涉及蛋白质在大脑中积累和聚集的神经退行性疾病的方法，如阿尔茨海默病、帕金森病和亨廷顿病。
• Nonpeptidic Lysosomal Modulators Derived from Z-Phe-Ala-Diazomethylketone for Treating Protein Accumulation Diseases
  作者：Kishore Viswanathan、Dennis J. Hoover、Jeannie Hwang、Meagan L. Wisniewski、Uzoma S. Ikonne、Ben A. Bahr、Dennis L. Wright

  DOI：10.1021/ml300197h

  日期：2012.11.8

  Lysosomes are involved in protein turnover and removing misfolded species, and their enzymes have the potential to offset the defect in proteolytic clearance that contributes to the age-related dementia Alzheimer's disease (AD). The weak cathepsin B and L inhibitor Z-Phe-Ala-diazomethylketone (PADK) enhances lysosomal cathepsin levels at low concentrations, thereby eliciting protective clearance of PHF-tau and A beta 42 in the hippocampus and other brain regions. Here, a class of positive modulators is established with compounds decoupled from the cathepsin inhibitory properties. We utilized PADK as a departure point to develop nonpeptidic structures with the hydroxyethyl isostere. The first-in-class modulators SD1002 and SD1003 exhibit: : improved levels of cathepsin up-regulation but almost complete removal of cathepsin inhibitory properties as compared to PADK. Isomers of the lead compound SD1002 were synthesized, and the modulatory activity was determined to be stereoselective. In addition, the lead compound was tested in transgenic mice with results indicating protection against AD-type protein accumulation pathology.
• Discovery of a novel class of potent HIV-1 protease inhibitors containing the (R)-(hydroxyethyl)urea isostere
  作者：Daniel P. Getman、Gary A. DeCrescenzo、Robert M. Heintz、Kathryn L. Reed、John J. Talley、Martin L. Bryant、Michael Clare、Kathryn A. Houseman、J. Joseph Marr

  DOI：10.1021/jm00054a014

  日期：1993.1
• Inhibitors of HIV-1 Protease Containing the Novel and Potent (R)-(Hydroxyethyl)sulfonamide Isostere
  作者：Michael L. Vazquez、Martin L. Bryant、Michael Clare、Gary A. DeCrescenzo、Elizabeth M. Doherty、John N. Freskos、Daniel P. Getman、Kathryn A. Houseman、Janet A. Julien、Geralyn P. Kocan、Richard A. Mueller、Huey-Sheng Shieh、William C. Stallings、Roderick A. Stegeman、John J. Tilley

  DOI：10.1021/jm00004a001

  日期：1995.2