(R)-S-(2-nitrophenyl)-N-(tert-butyloxycarbonyl)cysteine | 356548-98-6

• 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: (R)-S-(2-nitrophenyl)-N-(tert-butyloxycarbonyl)cysteine
• 英文别名: (2R)-2-[(tert-butoxycarbonyl)amino]-3-[(2-nitrophenyl)sulfanyl]propanoic acid；(R)-2-((tert-butoxycarbonyl)amino)-3-((2-nitrophenyl)thio)propanoic acid；(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(2-nitrophenyl)sulfanylpropanoic acid
• CAS: 356548-98-6
• 化学式: C₁₄H₁₈N₂O₆S
• 分子量: 342.373
• InChiKey: DPXKFRBVNAOQQV-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  147
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-S-(2-nitrophenyl)-N-(tert-butyloxycarbonyl)cysteine 在 铁粉 、 氯化铵 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 (R)-S-(2-aminophenyl)-N-(tert-butyloxycarbonyl)cysteine
  参考文献：
  名称：

  设计，合成和生物评价1，5-苯并硫氮杂-4-酮衍生物靶向因子VIIa /组织因子

  摘要：

  1，5-苯并硫氮杂-4-酮骨架被证明可以提供有效的蛋白酶抑制剂。在这项贡献中，我们描述了其在因子VIIa /组织因子抑制剂设计中的用途。一系列在其芳基部分包含未取代的支架的化合物导致化合物20的IC 50为2.16μM。在对该化合物进行分子建模研究之后，制备了第二个化合物，需要合成受保护的7-或8-取代的1,5-苯并噻氮杂-4-酮衍生物。

  DOI：

  10.1016/j.bmcl.2009.01.039
• 作为产物：
  描述：

  N-acetyl-S-(2-nitro-phenyl)-L-cysteine 在 硫酸 、 碳酸氢钠 作用下， 以 1,4-二氧六环 为溶剂， 生成 (R)-S-(2-nitrophenyl)-N-(tert-butyloxycarbonyl)cysteine
  参考文献：
  名称：

  S-Aryl cysteine S,S-dioxides as inhibitors of mammalian kynureninase

  摘要：

  A series of 2-amino-S-aryl cysteine S,S-dioxides have been synthesised and shown to inhibit kynureninase an important enzyme in the biosynthesis of the known excitotoxic moiety quinolinic acid. The most potent of these, 2-amino-5-methyl-S-phenyl cysteine S,S-dioxide 6d, inhibits interferon-gamma induced synthesis of quinolinic acid in human macrophages. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(97)10209-8
• 作为试剂：
  描述：

  BOC-L-半胱氨酸 、 碳酸氢钠 、 1-氟-2-硝基苯 在 乙醇 、 水 、 乙醚 、 二氯甲烷 、 Brine 、 Sodium sulfate-III 、 (R)-S-(2-nitrophenyl)-N-(tert-butyloxycarbonyl)cysteine 作用下， 以 水 、 乙醇 为溶剂， 反应 4.0h， 以to afford the title compound as yellow solid (R)-2-((tert-butoxycarbonyl)amino)-3-((2-nitrophenyl)thio)propanoic acid (7 g, 20.4 mmol, 90% yield)的产率得到(R)-S-(2-nitrophenyl)-N-(tert-butyloxycarbonyl)cysteine
  参考文献：
  名称：

  HETEROCYCLIC AMIDES AS KINASE INHIBITORS

  摘要：

  本发明涉及以下公式的化合物：其中X、Y、Z1、Z2、Z3、Z4、R5、RA、m、A、L和B的定义如本文所述，以及制备和使用它们的方法。

  公开号：

  US20150353533A1

文献信息

• [EN] HETEROCYCLIC AMIDES AS KINASE INHIBITORS<br/>[FR] AMIDES HÉTÉROCYCLIQUES À UTILISER EN TANT QU'INHIBITEURS DE KINASE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2014125444A1

  公开（公告）日：2014-08-21

  Disclosed are compounds having the formula (I) wherein X, Y, Z1, Z2, Z3, Z4, R5, RA, m, A. L, and B are as defined herein, and methods of making and using the same.

  揭示了具有式（I）的化合物，其中X、Y、Z1、Z2、Z3、Z4、R5、RA、m、A、L和B如本文所定义，并公开了制备和使用这些化合物的方法。
• Heterocyclic amides as kinase inhibitors
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US10292987B2

  公开（公告）日：2019-05-21

  Disclosed are compounds having the formula: wherein X, Y, Z1, Z2, Z3, Z4, R5, RA, m, A. L, and B are as defined herein, and methods of making and using the same.

  所公开的是具有以下式子的化合物 其中 X、Y、Z1、Z2、Z3、Z4、R5、RA、m、A. L 和 B 如本文所定义，以及制造和使用它们的方法。
• Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases
  作者：Philip A. Harris、Scott B. Berger、Jae U. Jeong、Rakesh Nagilla、Deepak Bandyopadhyay、Nino Campobasso、Carol A. Capriotti、Julie A. Cox、Lauren Dare、Xiaoyang Dong、Patrick M. Eidam、Joshua N. Finger、Sandra J. Hoffman、James Kang、Viera Kasparcova、Bryan W. King、Ruth Lehr、Yunfeng Lan、Lara K. Leister、John D. Lich、Thomas T. MacDonald、Nathan A. Miller、Michael T. Ouellette、Christina S. Pao、Attiq Rahman、Michael A. Reilly、Alan R. Rendina、Elizabeth J. Rivera、Michelle C. Schaeffer、Clark A. Sehon、Robert R. Singhaus、Helen H. Sun、Barbara A. Swift、Rachel D. Totoritis、Anna Vossenkämper、Paris Ward、David D. Wisnoski、Daohua Zhang、Robert W. Marquis、Peter J. Gough、John Bertin

  DOI：10.1021/acs.jmedchem.6b01751

  日期：2017.2.23

  RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, we report our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clinical candidate GSK2982772 (compound 5), currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound 5 potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking many TNF-dependent cellular responses. Highlighting, its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants. The highly favorable physicochemical and ADMET properties of 5, combined with high potency, led to a predicted low oral dose in humans.
• Design, Synthesis, and Structure−Activity Relationships of Macrocyclic Hydroxamic Acids That Inhibit Tumor Necrosis Factor α Release in Vitro and in Vivo
  作者：Chu-Biao Xue、Matthew E. Voss、David J. Nelson、James J.-W. Duan、Robert J. Cherney、Irina C. Jacobson、Xiaohua He、John Roderick、Lihua Chen、Ronald L. Corbett、Li Wang、Dayton T. Meyer、Kenneth Kennedy、William F. DeGrado、Karl D. Hardman、Christopher A. Teleha、Bruce D. Jaffee、Rui-Qin Liu、Robert A. Copeland、Maryanne B. Covington、David D. Christ、James M. Trzaskos、Robert C. Newton、Ronald L. Magolda、Ruth R. Wexler、Carl P. Decicco

  DOI：10.1021/jm010127e

  日期：2001.8.1

  To search for TNF-alpha (tumor necrosis factor alpha) converting enzyme (TACE) inhibitors, we designed a new class of macrocyclic hydroxamic acids by linking the PI and P2 ' residues of acyclic anti-succinate-based hydroxamic acids. A variety of residues including amide, carbamate, alkyl, sulfonamido, Boc-amino, and amino were found to be suitable P1-P2 ' linkers. With an N-methylamide at P3 ', the 13-16-membered macrocycles prepared exhibited low micromolar activities in the inhibition of TNF-alpha release from LPS-stimulated human whole blood. Further elaboration in the P3 ' -P4 ' area using the cyclophane and cyclic carbamate templates led to the identification of a number of potent analogues with IC50 values of less than or equal to 0.2 muM in whole blood assay (WBA). Although the P3 ' area can accommodate a broad array of structurally diversified functional groups including polar residues, hydrophobic residues, and amino and carboxylic acid moieties, in both the cyclophane series and the cyclic carbamate series, a glycine residue at P3 ' was identified as a critical structural component to achieve both good in vitro potency and good oral activity. With a glycine residue at P3 ', an N-methylamide at P4 ' provided the best cyclophane analogue, SL422 (WBA IC50 = 0.22 muM, LPS-mouse ED50 = 15 mg/kg, po), whereas a morpholinylamide at P4 ' afforded the most potent and most orally active cyclic carbamate analogue, SP057 (WBA IC50 = 0.067 muM, LPS-mouse ED50 = 2.3 mg/kg, po). Further profiling for SL422 and SP057 showed that these macrocyclic compounds are potent TACE inhibitors, with K-i values of 12 and 4.2 nM in the porcine TACE assay, and are broad-spectrum MMP inhibitors. Pharmacokinetic studies in beagle dogs revealed that SL422 and SP057 are orally bioavailable, with oral bioavailabilities of 11% and 23%, respectively.
• AN IMPROVED SYNTHESIS OF (S)- OR (R)-N-BcE-PROTECTED 1,5-BENZOTHIAZEPINE DERIVATIVES
  作者：Muriel Amblard、Monique Calmès、Virginie Roques、Samuel Tabet、Albert Loffet、Jean Martinez

  DOI：10.1080/00304940209458076

  日期：2002.8.1