syn-(2S)-β-hydroxyleucine | 35016-62-7

• 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: syn-(2S)-β-hydroxyleucine
• 英文别名: (2SR,3RS)-2-amino-3-hydroxy-4-methylpentanoic acid；(+/-)-threo-β-hydroxyleucine；(+/-)-threo-3-hydroxyleucine；(+/-)-threo-2-amino-3-hydroxy-4-methyl-valeric acid；(+/-)-threo-2-Amino-3-hydroxy-4-methyl-valeriansaeure
• CAS: 35016-62-7
• 化学式: C₆H₁₃NO₃
• 分子量: 147.17
• InChiKey: ZAYJDMWJYCTABM-CRCLSJGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  syn-(2S)-β-hydroxyleucine 在 sodium hydroxide 、 氯甲酸苄酯 作用下， 生成 (+/-)-threo-2-benzyloxycarbonylamino-3-hydroxy-4-methyl-valeric acid
  参考文献：
  名称：

  Wieland et al., Chemische Berichte, 1954, vol. 87, p. 1312,1317

  摘要：

  DOI：
• 作为产物：
  描述：

  (2E)-4-methylpent-2-enoic acid 在 氨 、 水 、 溴 作用下， 生成 syn-(2S)-β-hydroxyleucine
  参考文献：
  名称：

  Buston; Bishop, Journal of Biological Chemistry, 1955, vol. 215, p. 217,218

  摘要：

  DOI：

文献信息

• CONFORMATIONALLY CONSTRAINED, FULLY SYNTHETIC MACROCYCLIC COMPOUNDS
  申请人：POLYPHOR AG

  公开号：US20150051183A1

  公开（公告）日：2015-02-19

  The conformationally restricted, spatially defined macrocyclic ring system of formula (I) is constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. Macrocycles described by this ring system I are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), inhibitory activity on enzymes or antimicrobial activity. In particular, these macrocycles show inhibitory activity on endothelin converting enzyme of subtype 1 (ECE-1) and/or the cysteine protease cathepsin S (CatS), and/or act as antagonists of the oxytocin (OT) receptor, thyrotropin-releasing hormone (TRH) receptor and/or leukotriene B4 (LTB4) receptor, and/or as agonists of the bombesin 3 (BB3) receptor, and/or show antimicrobial activity against at least one bacterial strain. Thus they are showing great potential as medicaments for a variety of diseases.

  公式（I）的构象受限、空间定义的大环环系统由三个不同的分子部分组成：模板A、构象调节剂B和桥C。由这种环系统I描述的大环可通过并行合成或溶液中或固相上的组合化学轻松制造。它们被设计用于与各种特定生物靶标类相互作用，例如在G蛋白偶联受体（GPCR）上的激动或拮抗活性，酶的抑制活性或抗菌活性。特别是，这些大环显示对亚型1的内皮素转化酶（ECE-1）和/或半胱氨酸蛋白酶卡特普辛S（CatS）的抑制活性，和/或作为催产素（OT）受体、促甲状腺释放激素（TRH）受体和/或白三烯B4（LTB4）受体的拮抗剂，和/或作为瘤胃素3（BB3）受体的激动剂，和/或对至少一种细菌菌株显示抗菌活性。因此，它们显示出作为各种疾病药物的巨大潜力。
• Total Synthesis of the Cyclic Depsipeptide YM-280193, a Platelet Aggregation Inhibitor
  作者：Harveen Kaur、Paul W. R. Harris、Peter J. Little、Margaret A. Brimble

  DOI：10.1021/ol503507g

  日期：2015.2.6

  first total synthesis of YM-280193, a cyclic depsipeptide that inhibits the ADP-induced aggregation of human platelets, is described. The monomer and dipeptide fragments were prepared using conventional chemistry and subsequently assembled by Fmoc-solid-phase peptide synthesis (Fmoc-SPPS). A late-stage novel bis-alkylation–elimination of cysteine on-resin was employed to introduce the unnatural N-methyldehydroalanine

  描述了YM-280193的第一个全合成，这是一种环状的二肽，可抑制ADP诱导的人血小板聚集。使用常规化学方法制备单体和二肽片段，然后通过Fmoc-固相肽合成（Fmoc-SPPS）进行组装。一种新型的半烷基树脂上的双烷基化消除后期方法被用来引入非天然的N-甲基脱氢丙氨酸部分。最后一步涉及在受阻碍的非天然N，O-二甲基苏氨酸和β-羟基亮氨酸残基之间进行关键的大内酰胺化反应。
• [EN] DISUBSTITUTED BETA-LACTONES AS INHIBITORS OF N-ACYLETHANOLAMINE ACID AMIDASE (NAAA)<br/>[FR] BÊTA-LACTONES DISUBSTITUÉS EN TANT QU'INHIBITEURS DE L'AMIDASE ACIDE DE N-ACYLÉTHANOLAMINE (NAAA)
  申请人：UNIV CALIFORNIA

  公开号：WO2013078430A1

  公开（公告）日：2013-05-30

  The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.

  本发明提供了用于抑制N-酰乙醇胺酸酰胺酶（NAAA）的化合物和药物组合物。考虑到抑制NAAA是一种维持棕榈酰乙醇胺（PEA）和油酰乙醇胺（OEA）水平的方法，这两种物质是NAAA的底物，在特征为PEA和OEA浓度降低的情况下。该发明还提供了治疗炎症性疾病和疼痛以及其他与降低PEA和OEA水平相关的疾病的方法。
• Deciphering Specificity Determinants for FR900359-Derived G_qα Inhibitors Based on Computational and Structure-Activity Studies
  作者：Raphael Reher、Toni Kühl、Suvi Annala、Tobias Benkel、Desireé Kaufmann、Britta Nubbemeyer、Justin Patrick Odhiambo、Pascal Heimer、Charlotte Anneke Bäuml、Stefan Kehraus、Max Crüsemann、Evi Kostenis、Daniel Tietze、Gabriele M. König、Diana Imhof

  DOI：10.1002/cmdc.201800304

  日期：2018.8.20

  identified unique features in the macrocyclic structures responsible for binding to the target protein correlating with inhibitory activity. While all novel compounds were devoid of effects on Gi and Gs proteins, no inhibitor surpassed the biological activity of FR. This raises the question of whether depsipeptides such as FR already represent valuable chemical tools for specific inhibition of Gq and, at

  化学工具直接靶向G蛋白偶联受体的细胞内Gα亚基是当前药理学研究和新型治疗方法开发中的一项艰巨任务。在这项研究中，我们分析了来自天然来源的，合成的环肽，以及所有的迄今为止已知G新颖的基于FR900359-类似物q α中的综合研究抑制剂，设计一种用于决定相互作用与和抑制特性的阐明的策略特定FR / YM装订袋中的G q。使用2D NMR光谱学和分子对接，我们确定了大环结构中与结合抑制活性相关的靶蛋白结合的独特特征。虽然所有新化合物都没有对G i产生影响和G s蛋白，没有任何抑制剂能超过FR的生物学活性。这就提出了这样的问题，即脱肽肽（例如FR）是否已经代表了对Gq进行特异性抑制的有价值的化学工具，并且同时又是合适的天然先导结构，用于开发靶向Gq以外的Gα亚基的新型化合物。
• Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
  申请人：The Regents of the University of California

  公开号：US09353075B2

  公开（公告）日：2016-05-31

  The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.

  本发明提供了用于抑制N-酰基乙醇胺酸酰胺酶（NAAA）的化合物和药物组合物。考虑到抑制NAAA是一种维持棕榈酰乙醇胺（PEA）和油酰乙醇胺（OEA）水平的方法，在特征为PEA和OEA浓度降低的情况下。该发明还提供了治疗炎症性疾病和疼痛以及其他与降低PEA和OEA水平相关的紊乱的方法。