(S)-2-<(tert-butoxycarbonyl)amino>-3-(1-naphthylthio)propionic acid | 172882-66-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-<(tert-butoxycarbonyl)amino>-3-(1-naphthylthio)propionic acid
• 英文别名: (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-naphthalen-1-ylsulfanylpropanoic acid
• CAS: 172882-66-5
• 化学式: C₁₈H₂₁NO₄S
• 分子量: 347.435
• InChiKey: DKFAMJBIGKASMA-CQSZACIVSA-N

物化性质

• 沸点：
  547.4±45.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-<(tert-butoxycarbonyl)amino>-3-(1-naphthylthio)propionic acid 在 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 2-[(2R,3S)-3-[[(2S)-2-amino-3-naphthalen-1-ylsulfanylpropanoyl]amino]-2-hydroxy-4-phenylbutyl]-N-tert-butylbenzamide
  参考文献：
  名称：

  Potent Human Immunodeficiency Virus Type 1 Protease Inhibitors That Utilize Noncoded d-Amino Acids as P₂/P₃ Ligands

  摘要：

  Noncoded D-amino acids have been designed to replace the quinaldic amide-asparaginyl moiety (P-2/P-3 ligand) found in several potent human immunodeficiency virus (HIV) protease inhibitors such as LY289612. The substituted nitrogen, optimally an N-methanesulfonyl moiety, served as a CH2CONH2 (asparagine side chain mimic), while the amino acid side chain became the backbone and P-3 ligand of these novel inhibitors. Compounds derived from S-aryl-D-cysteine proved to be patent HIV protease inhibitors which also exhibited potent whole cell antiviral activity. Oxidation of the cysteines to the sulfoxide or sulfone oxidation states resulted in significant improvements in potency. For example, the compound derived from N-(methylsulfonyl)-2-S-naphthylcysteine sulfone, 17c, was a 3.5 nM inhibitor of HIV protease which inhibited the spread of virus in MT4 cells with an IC50 = 4.3 nM. Compounds 17c,g,i were found to be orally bioavailable in a rat model.

  DOI：

  10.1021/jm950576c
• 作为产物：
  描述：

  1-奈硫酚 、 N-叔丁氧羰基-D-丝氨酸(Β-内酯) 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 生成 (S)-2-<(tert-butoxycarbonyl)amino>-3-(1-naphthylthio)propionic acid
  参考文献：
  名称：

  Combination of Non-natural d-Amino Acid Derivatives and Allophenylnorstatine−Dimethylthioproline Scaffold in HIV Protease Inhibitors Have High Efficacy in Mutant HIV

  摘要：

  Several non-natural D-amino acid derivatives were introduced as P(2)/P(3) residues in allophenylnorstatine-containing (Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid) HIV protease inhibitors. The synthetic analogues exhibited potent inhibitory activity against HIV-1 protease enzyme and HIV-1 replication in MT-4 cells. Structure-activity relationships revealed that D-cysteine or serine derivatives contributed to highly potent anti-HIV activities. Interestingly, anti-HIV activity of all the D-amino acid-introduced inhibitors was remarkably enhanced in their anti-HIV activities against a Nelfinavir-resistant clone, which has a D30N mutation in the protease, over that of the wild-type strain. HIV inhibitory activity of several analogues was moderately affected by an inclusion of alpha(1)-acid glycoprotein in the test medium.

  DOI：

  10.1021/jm701555p

文献信息

• Synthesis and antiviral property of allophenylnorstatine-based HIV protease inhibitors incorporating d-cysteine derivatives as P2/P3 moieties
  作者：Ei’ichi Ami、Koichiro Nakahara、Akihiko Sato、Jeffrey-Tri Nguyen、Koushi Hidaka、Yoshio Hamada、Shingo Nakatani、Tooru Kimura、Yoshio Hayashi、Yoshiaki Kiso

  DOI：10.1016/j.bmcl.2007.05.039

  日期：2007.8

  We designed several HIV protease inhibitors with various D-cysteine derivatives as P-2/P-3 moieties based on the structure of clinical drug candidate, KNI-764. Herein, we report their synthesis, HIV protease inhibitory activity, HIV 11113 cell inhibitory activity, cellular toxicity, and inhibitory activity against drug-resistant HIV strains. KNI-1931 showed distinct selectivity against HIV proteases and high potency against drug-resistant strains, surpassing those of Ritonavir and Nelfinavir. (c) 2007 Elsevier Ltd. All rights reserved.