N-(4-pyridinylcarbonyl)-L-leucine | 98874-02-3

• 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-(4-pyridinylcarbonyl)-L-leucine
• 英文别名: isonicotinoyl-L-Leu；(2S)-4-methyl-2-(pyridine-4-carbonylamino)pentanoic acid
• CAS: 98874-02-3
• 化学式: C₁₂H₁₆N₂O₃
• mdl: MFCD00699984
• 分子量: 236.271
• InChiKey: MRKWNSZYBWBVCJ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  79.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  L-缬氨酸甲酯盐酸盐 、 N-(4-pyridinylcarbonyl)-L-leucine 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以81%的产率得到isonicotinoyl L-Leu-L-Val-OMe
  参考文献：
  名称：

  El-Naggar; Hussein; El-Nemma, Farmaco, Edizione Scientifica, 1985, vol. 40, # 9, p. 662 - 670

  摘要：

  DOI：
• 作为产物：
  描述：

  N-(4-pyridinylcarbonyl)-L-leucine phenylmethyl ester 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 5.0h， 以97%的产率得到N-(4-pyridinylcarbonyl)-L-leucine
  参考文献：
  名称：

  Microwave-assisted synthesis of pyridylpyrroles from N-acylated amino acids

  摘要：

  A small library of 3- and 4-pyridyl-substituted pyrroles was prepared from N-acylated amino acids. Nicotinoyl or isonicotinoyl chloride was used for the N-acylation of benzyl esters of amino acids. Debenzylation by palladium-catalyzed hydrogenation gave N-acylated amino acids. Dehydration of the acylated amino acids gave cyclic intermediates, manchnones or aziactones, which were treated in situ with alkynes in 1,3-dipolar cycloadditions. The starting materials were prepared in a parallel fashion, and microwave irradiation was used to facilitate the cycloaddition reactions. The regiochemistry of the cycloaddition was studied. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.09.094

文献信息

• Subnanomolar Cathepsin S Inhibitors with High Selectivity: Optimizing Covalent Reversible α‐Fluorovinylsulfones and α‐Sulfonates as Potential Immunomodulators in Cancer
  作者：Natalie Fuchs、Mergim Meta、Bellinda Lantzberg、Matthias Bros、Seah Ling Kuan、Tanja Weil、Tanja Schirmeister

  DOI：10.1002/cmdc.202300160

  日期：2023.8

  The cysteine protease cathepsin S (CatS) is overexpressed in many tumors. It is known to be involved in tumor progression as well as antigen processing in antigen‐presenting cells (APC). Recent evidence suggests that silencing CatS improves the anti‐tumor immune response in several cancers. Therefore, CatS is an interesting target to modulate the immune response in these diseases. Here, we present a series of covalent‐reversible CatS inhibitors based on the α‐fluorovinylsulfone and ‐sulfonate warheads. We optimized two lead structures by molecular docking approaches, resulting in 22 final compounds which were evaluated in fluorometric enzyme assays for CatS inhibition and for selectivity towards the off‐targets CatB and CatL. The most potent inhibitor in the series has subnanomolar affinity (K_i=0.08 nM) and more than 100,000‐fold selectivity towards cathepsins B and L. These new reversible and non‐cytotoxic inhibitors could serve as interesting leads to develop new immunomodulators in cancer therapy.

  摘要半胱氨酸蛋白酶 cathepsin S（CatS）在许多肿瘤中过度表达。众所周知，它参与了肿瘤的进展以及抗原递呈细胞（APC）的抗原处理。最近的证据表明，沉默 CatS 可以改善几种癌症的抗肿瘤免疫反应。因此，CatS 是调节这些疾病免疫反应的一个有趣靶点。在此，我们介绍了一系列基于α-氟乙烯砜和-磺酸盐弹头的共价可逆 CatS 抑制剂。我们通过分子对接方法优化了两种先导结构，最终得到了 22 种化合物，并在荧光酶测定法中评估了它们对 CatS 的抑制作用以及对非靶标 CatB 和 CatL 的选择性。该系列中最有效的抑制剂具有亚摩尔亲和力（Ki=0.08 nM），对Cathepsins B和L的选择性超过100,000倍。
• Solid-phase synthesis of 1,3-diamino ketones
  作者：Chakrapani Subramanyam、Shang-Poa Chang

  DOI：10.1016/s0040-4039(00)01262-4

  日期：2000.9

  A versatile solid-phase methodology for the synthesis of 1,3-diamino ketone class of cysteine protease inhibitors is reported. (C) 2000 Elsevier Science Ltd. All rights reserved.
• D-AMPHETAMINE COMPOUNDS, COMPOSITIONS, AND PROCESSES FOR MAKING AND USING THE SAME
  申请人：KemPharm, Inc.

  公开号：EP4051269A1

  公开（公告）日：2022-09-07
• [EN] D-AMPHETAMINE COMPOUNDS, COMPOSITIONS, AND PROCESSES FOR MAKING AND USING THE SAME<br/>[FR] COMPOSÉS DE D-AMPHÉTAMINE, COMPOSITIONS ET PROCÉDÉS DE FABRICATION ET D'UTILISATION CORRESPONDANTS
  申请人：KEMPHARM INC

  公开号：WO2021086426A1

  公开（公告）日：2021-05-06

  Disclosed are d-amphetamine compounds and compositions comprising at least one organic acid covalently bound to d-amphetamine, a salt thereof, a derivative thereof, or a combination thereof. Methods of making and using the same are also disclosed.
• El-Naggar; Hussein; El-Nemma, Farmaco, Edizione Scientifica, 1985, vol. 40, # 9, p. 662 - 670
  作者：El-Naggar、Hussein、El-Nemma、Samour

  DOI：——

  日期：——