(S)-3-(<(tert-butoxy)carbonyl>amino)-1-diazo-5-phenylpentan-2-one | 162818-40-8

• 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: (S)-3-(<(tert-butoxy)carbonyl>amino)-1-diazo-5-phenylpentan-2-one
• 英文别名: tert-butyl (S)-3-diazo-2-oxo-1-phenethylpropylcarbamate；tert-butyl N-[(3S)-1-diazo-2-oxo-5-phenylpentan-3-yl]carbamate
• CAS: 162818-40-8
• 化学式: C₁₆H₂₁N₃O₃
• 分子量: 303.361
• InChiKey: OVGSJDGKQXEDTK-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  57.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-(<(tert-butoxy)carbonyl>amino)-1-diazo-5-phenylpentan-2-one 在 盐酸 、 18-冠醚-6 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 [(3S)-2-oxo-5-phenyl-3-[[(2S)-4-phenyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]pentyl] acetate
  参考文献：
  名称：

  Synthesis, biological evaluation, hydration site thermodynamics, and chemical reactivity analysis of α-keto substituted peptidomimetics for the inhibition of Plasmodium falciparum

  摘要：

  A new series of peptidomimetic pseudo-prolyl-homophenylalanylketones were designed, synthesized and evaluated for inhibition of the Plasmodium falciparum cysteine proteases falcipain-2 (FP-2) and falcipain-3 (FP-3). In addition, the parasite killing activity of these compounds in human blood-cultured P. falciparum was examined. Of twenty-two (22) compounds synthesized, one peptidomimetic comprising a homophenylalanine-based a-hydroxyketone linked Cbz-protected hydroxyproline (39) showed the most potency (IC50 80 nM against FP-2 and 60 nM against FP-3). In silico analysis of these peptidomimetic analogs offered important protein-ligand structural insights including the role, by WaterMap, of water molecules in the active sites of these protease isoforms. The pseudo-dipeptide 39 and related compounds may serve as a promising direction forward in the design of competitive inhibitors of falcipains for the effective treatment of malaria. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.062
• 作为产物：
  描述：

  Boc-L-高苯丙氨酸 在 N-methylmorpholinepolystyrene 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (S)-3-(<(tert-butoxy)carbonyl>amino)-1-diazo-5-phenylpentan-2-one
  参考文献：
  名称：

  通过三氟甲磺酸金属盐催化的分子内重氮羰基分子插入反应，由Boc保护的氨基酸有效合成环状氨基甲酸酯

  摘要：

  本文描述了由重氮酮3a - 1简单有效地合成环状氨基甲酸酯和相关的恶嗪酮1a - l的方法。该转化涉及在分子内重氮羰基插入反应中使用金属三氟甲磺酸酯通过重氮基团的活化而生成羧甲酸酯，总收率很高。

  DOI：

  10.1016/j.tetlet.2006.08.111

文献信息

• Novel compounds and compositions as protease inhibitors
  申请人：Axys Pharmaceuticals, Inc.

  公开号：US20030092634A1

  公开（公告）日：2003-05-15

  The present invention relates to novel cysteine protease inhibitors; the pharmaceutically acceptable salts and N-oxides thereof; their uses as therapeutic agents and the methods of their making.

  本发明涉及新型半胱氨酸蛋白酶抑制剂；其药学上可接受的盐和N-氧化物；它们作为治疗剂的用途和其制备方法。
• Compounds and compositions as protease inhibitors
  申请人：Axys Pharmaceuticals, Inc.

  公开号：US06506733B1

  公开（公告）日：2003-01-14

  Compounds of the formula: are provided, and are useful as cysteine protease inhibitors, particularly in the treatment of diseases such as osteoporosis or autoimmune disorders in which cathepsins K or S contribute to the pathology or symptomatolgy of the disease.

  提供了化合物的公式，这些化合物在半胱氨酸蛋白酶抑制剂方面非常有用，特别是在治疗像骨质疏松症或自身免疫性疾病这样的疾病中，其中卡特普西林K或S对疾病的病理学或症状学起到贡献。
• Oh, Seikwan; Jung, Jae-Chul, Zeitschrift fur Naturforschung, B: Chemical Sciences, 2008, vol. 63, # 2, p. 210 - 216
  作者：Oh, Seikwan、Jung, Jae-Chul

  DOI：——

  日期：——
• Novel route to the synthesis of peptides containing 2-amino-1′-hydroxymethyl ketones and their application as cathepsin K inhibitors
  作者：Rohan V Mendonca、Shankar Venkatraman、James T Palmer

  DOI：10.1016/s0960-894x(02)00611-x

  日期：2002.10

  Cathepsin K is highly expressed in human osteoclasts, and is implicated in bone resorption. This makes it an attractive target for the treatment of osteoporosis. Peptides containing 2-amino-1'-hydroxymethyl ketones and 2-amino-1'-alkoxymethyl ketones were discovered as potent inhibitors of cathepsin K. A novel synthetic route was devised to facilitate rapid elucidation of the SAR of these inhibitors. The synthesis and SAR of hydroxymethyl ketones are presented. (C) 2002 Elsevier Science Ltd. All rights reserved.
• (S)-β3-Homolysine- and (S)-β3-Homoserine-Containingβ-Peptides: CD Spectra in Aqueous Solution
  作者：Stefan Abele、Gilles Guichard、Dieter Seebach

  DOI：10.1002/(sici)1522-2675(19981216)81:12<2141::aid-hlca2141>3.0.co;2-5

  日期：1998.12.16

  For further structural studies and for physiological investigations of beta-peptides, it is necessary to have H2O-soluble derivatives. Thus, we have prepared beta-hexa-, beta-hepta-, and beta-nonapeptides (1-6) with two, three, and seven side chains of lysine and serine. To detect possible pi-pi interactions, we also included the beta-amino acid beta(2)-HHop, resulting from homologation of so-called homophenylalanine (Hop) (5 and 6). The Fmoc-beta(2)- and beta(3)-amino-acid derivatives (11-14 and 19), and the corresponding beta-peptides were prepared by methods previously described (solid-phase peptide coupling; HPLC-pure samples, Fig. I). Circular-dichroism spectra (Fig.2) indicate the presence of less pronounced secondary structures (especially of the lysine analogues with multiple positive charge) in H2O as compared to MeOH. The beta(3)-heptapeptide (3) with two serine side chains is well soluble in H2O and exhibits the CD pattern typical of the 3(1)-helical structure.