N-benzyl-β-amino-α-hydroxy-amide | 859403-80-8

• 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: N-benzyl-β-amino-α-hydroxy-amide
• 英文别名: (2R,3S)-3-amino-N-benzyl-2-hydroxy-4-phenylbutanamide
• CAS: 859403-80-8
• 化学式: C₁₇H₂₀N₂O₂
• 分子量: 284.358
• InChiKey: UHDSMWWEIRIUER-JKSUJKDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-benzyl-β-amino-α-hydroxy-amide 在 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 7-Methyl-8-oxo-2,3-dihydro-8H-1,4,5-trioxa-anthracene-6-carboxylic acid ((S)-1-benzyl-2-benzylcarbamoyl-2-oxo-ethyl)-amide
  参考文献：
  名称：

  Synthesis and biological evaluation of chromone carboxamides as calpain inhibitors

  摘要：

  Excessive calpain activations contribute to serious cellular damage and have been found in many pathological conditions. Novel chromone carboxamides derived from ketoamides were prepared and evaluated for mu-calpain inhibition. Among synthesized, compound 2i was the most potent calpain inhibitor with an IC50 value of 0.24 +/- 0.11 mu M comparable to the activity of peptide aldehyde calpain inhibitor MDL 28,170. Furthermore, compound 2i showed higher selectivity for mu-calpain over two related cysteine proteases cathepsin B and cathepsin L, suggesting the chromone ring as a good scaffold for selective mu-calpain inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.095
• 作为产物：
  描述：

  ((1S,2R)-1-Benzyl-2-benzylcarbamoyl-2-hydroxy-ethyl)-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 N-benzyl-β-amino-α-hydroxy-amide
  参考文献：
  名称：

  KMI-358 and KMI-370, highly potent and small-sized BACE1 inhibitors containing phenylnorstatine

  摘要：

  Recently, we reported a novel substrate-based octapeptide BACE1 inhibitor KMI-008 containing hydroxy-methylcarbonyl (HMC) isostere as a transition-state mimic. Using KMI-008 as a lead compound, a small-sized and highly potent BACE I inhibitor KMI-370 (IC50 = 3.4 nM) was designed and synthesized. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.12.088

文献信息

• Rational repurposing, synthesis, <i>in vitro</i> and <i>in silico</i> studies of chromone-peptidyl hybrids as potential agents against <i>Leishmania donovani</i>
  作者：Ahmed H. E. Hassan、Waleed A. Bayoumi、Selwan M. El-Sayed、Trong-Nhat Phan、Yeon Ju Kim、Chae Hyeon Lee、Soo Bin Cho、Taegeun Oh、Gyeongpyo Ham、Kazem Mahmoud、Joo Hwan No、Yong Sup Lee

  DOI：10.1080/14756366.2023.2229071

  日期：2023.12.31

  Abstract A chromone-peptidyl hybrids series was synthesised and rationally repurposed towards identification of potential antileishmanial hits against visceral leishmaniasis. Three hybrids 7c, 7n, and 7h showed potential IC50 values (9.8, 10, and 12 µM, respectively) which were comparable to erufosine IC50 (9.8 µM) but lower potency than miltefosine IC50 (3.5 µM). Preliminary assessment of cytotoxicity

  摘要 合成了色酮-肽基杂合体系列，并合理地重新调整用途，以鉴定针对内脏利什曼病的潜在抗利什曼病。三种杂交体7c、7n和7h显示出潜在的 IC 50值（分别为 9.8、10 和 12 µM），与埃卢福辛 IC 50 (9.8 µM)相当，但效力低于米替福辛 IC 50 (3.5 µM)。使用人 THP-1 细胞对细胞毒性进行初步评估，发现色酮-肽杂合体7c和7n在高达 100 µM 时无细胞毒性，而埃吕福辛和米替福辛的 CC 50分别为 19.4 µM 和 >40 µM。计算机模拟研究指出，肽基部分的N - p-甲氧基苯乙基取代基以及色酮部分苯环的氧基取代功能是与Ld CALP 结合的关键因素。总之，这些发现表明色酮-肽基杂合体7c和7n作为潜在的和预期的非细胞毒性抗利什曼病命中化合物，可用于开发潜在的抗内脏利什曼病抗利什曼病药物。
• Design and synthesis of 4-quinolinone 2-carboxamides as calpain inhibitors
  作者：Dong Hyuk Nam、Kwang Seob Lee、Sang Hoon Kim、Sung Min Kim、Seo Yun Jung、Sung Hyun Chung、Hyoung Ja Kim、Nam Doo Kim、Changbae Jin、Yong Sup Lee

  DOI：10.1016/j.bmcl.2007.10.097

  日期：2008.1

  Calpains are involved in a variety of calcium-regulated cellular processes, such as signal transduction, cell proliferation, differentiation, and apoptosis. Excessive calpain activation contributes to serious cellular damage and has been reported in many pathological conditions. 4-Quinolinone 2-carboxamide derivatives were prepared and evaluated for mu-calpain inhibitory activities. Of the compounds synthesized, 3a and 3k, which possess a primary amide and 4-methoxyphenethyl amide at P-1' region, were found to most potently inhibit mu-calpain with IC50 values of 0.71 +/- 0.07 and 0.73 +/- 0.23 mu M, respectively. On the other hand, the incorporation of pyridine-containing amides decreased inhibitory activity. (C) 2007 Elsevier Ltd. All rights reserved.
• Synthesis of chromone carboxamide derivatives with antioxidative and calpain inhibitory properties
  作者：Sang Hoon Kim、Young Hoon Lee、Seo Yun Jung、Hyoung Ja Kim、Changbae Jin、Yong Sup Lee

  DOI：10.1016/j.ejmech.2011.02.025

  日期：2011.5

  The overactivation of mu-calpain can cause serious cell damage in several diseases. Furthermore, cell death in a number of neurodegenerative disorders is linked to the overproduction of reactive oxygen species. Therefore, antioxidants and mu-calpain inhibitors could have the therapeutic potentials to treat cell death related diseases. New chromone carboxamide derivatives 3 were synthesized to provide alternative mu-calpain inhibitors to compound 2, a conformationally constrained structural variant of MDL 28,170. Compounds 3h and 3l exhibited the most potent p-calpain inhibitory activities (IC50 = 0.09-0.10 mu M), and were comparable to 2 in this respect (IC50 = 0.07 mu M). Compound 31 showed both potent p-calpain inhibitory activity (IC50 = 0.28 mu M) and antioxidant activities in DPPH scavenging and lipid peroxidation inhibition assays. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Bestatin analogs-4-quinolinone hybrids as antileishmanial hits: Design, repurposing rational, synthesis, in vitro and in silico studies
  作者：Ahmed H.E. Hassan、Kazem Mahmoud、Trong-Nhat Phan、Moataz A. Shaldam、Chae Hyeon Lee、Yeon Ju Kim、Soo Bin Cho、Waleed A. Bayoumi、Selwan M. El-Sayed、Yeonwoo Choi、Suyeon Moon、Joo Hwan No、Yong Sup Lee

  DOI：10.1016/j.ejmech.2023.115211

  日期：2023.3

  their different molecular targets. Amongst type 1 bestatin analog-4-quinolone hybrids, hybrid 1e was identified as potential hit inhibiting growth of L. donovani promastigotes by 91 and 53% at 50 and 25 μM concentrations, respectively. Meanwhile, hybrid 2j was identified amongst type 2 bestatin analog-4-quinolone hybrids as potential hit compound inhibiting growth of L. donovani promastigotes by 50 and