N-phenylcysteine

• 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-phenylcysteine
• 英文别名: 3-Mercapto-2-phenylamino-propionic acid；2-anilino-3-sulfanylpropanoic acid
• 化学式: C₉H₁₁NO₂S
• 分子量: 197.258
• InChiKey: LGEYIBKMWLDPJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  50.3
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-phenylcysteine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 N-Boc-Trp-S-N-Ph-Cys-CONH-Me-Pyr
  参考文献：
  名称：

  [EN] NOVEL CYP34A-SPECIFIC INHIBITORS AND METHODS OF USING SAME
  [FR] NOUVEAUX INHIBITEURS SPÉCIFIQUES DU CYTOCHROME CYP3A4 ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本发明包括抑制CYP3A4的新型组合物。本发明还包括一种在需要的受试者中抑制CYP3A4的新方法，该方法包括向受试者施用本发明中化合物的有效量。在一个实施例中，受试者还会被施用至少一种额外的治疗药物。

  公开号：

  WO2017044742A1
• 作为产物：
  描述：

  硫代乙酰苯胺 在 氢溴酸 作用下， 以 甲苯 为溶剂， 生成 N-phenylcysteine
  参考文献：
  名称：

  [EN] NOVEL CYP34A-SPECIFIC INHIBITORS AND METHODS OF USING SAME
  [FR] NOUVEAUX INHIBITEURS SPÉCIFIQUES DU CYTOCHROME CYP3A4 ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本发明包括抑制CYP3A4的新型组合物。本发明还包括一种在需要的受试者中抑制CYP3A4的新方法，该方法包括向受试者施用本发明中化合物的有效量。在一个实施例中，受试者还会被施用至少一种额外的治疗药物。

  公开号：

  WO2017044742A1

文献信息

• Rational Design of CYP3A4 Inhibitors: A One-Atom Linker Elongation in Ritonavir-Like Compounds Leads to a Marked Improvement in the Binding Strength
  作者：Eric R. Samuels、Irina F. Sevrioukova

  DOI：10.3390/ijms22020852

  日期：——

  Inhibition of the major human drug-metabolizing cytochrome P450 3A4 (CYP3A4) by pharmaceuticals and other xenobiotics could lead to toxicity, drug–drug interactions and other adverse effects, as well as pharmacoenhancement. Despite serious clinical implications, the structural basis and attributes required for the potent inhibition of CYP3A4 remain to be established. We utilized a rational inhibitor design to investigate the structure–activity relationships in the analogues of ritonavir, the most potent CYP3A4 inhibitor in clinical use. This study elucidated the optimal length of the head-group spacer using eleven (series V) analogues with the R1/R2 side-groups as phenyls or R1–phenyl/R2–indole/naphthalene in various stereo configurations. Spectral, functional and structural characterization of the inhibitory complexes showed that a one-atom head-group linker elongation, from pyridyl–ethyl to pyridyl–propyl, was beneficial and markedly improved Ks, IC50 and thermostability of CYP3A4. In contrast, a two-atom linker extension led to a multi-fold decrease in the binding and inhibitory strength, possibly due to spatial and/or conformational constraints. The lead compound, 3h, was among the best inhibitors designed so far and overall, the strongest binder (Ks and IC50 of 0.007 and 0.090 µM, respectively). 3h was the fourth structurally simpler inhibitor superior to ritonavir, which further demonstrates the power of our approach.

  人体主要药物代谢细胞色素P450 3A4（CYP3A4）受药物和其他外源物质的抑制可能导致毒性、药物相互作用和其他不良影响，以及药效增强。尽管具有严重的临床意义，但对于CYP3A4的强效抑制所需的结构基础和属性尚未确定。我们利用合理的抑制剂设计来研究利托那韦类似物的结构活性关系，利托那韦是目前临床应用中最强效的CYP3A4抑制剂。这项研究阐明了头基间隔的最佳长度，使用了具有苯基或R1-苯基/R2-吲哚/萘基的不同立体构型的十一个（系列V）类似物。对抑制复合物的光谱、功能和结构特性的表征显示，头基连接物从吡啶基乙基延长到吡啶基丙基是有益的，并显著改善了CYP3A4的Ks、IC50和热稳定性。相比之下，两原子连接物的延长导致结合和抑制力量的多倍降低，可能是由于空间和/或构象限制。领先的化合物3h是迄今设计的最佳抑制剂之一，总体上是最强的结合剂（Ks和IC50分别为0.007和0.090 µM）。3h是第四种结构较简单的抑制剂，优于利托那韦，这进一步证明了我们方法的有效性。
• [EN] SUBSTITUTED CYCLOHEXENONES<br/>[FR] CYCLOHEXÉNONES SUBSTITUÉES
  申请人：FIRMENICH & CIE

  公开号：WO2009095804A1

  公开（公告）日：2009-08-06

  The present invention relates to a method of preparation of an optically active cyclohexenone derivative of Formula (I) O R 1 R 2 * R 1 and wherein R1 and R2 are organic residues.

  本发明涉及一种制备光学活性环己烯酮衍生物的方法，其化学式为（I）OR1R2*，其中R1和R2为有机残基。
• Processes for producing B-halogeno-a-amino-carboxylic acids and phenylcysteine derivatives and intermediates thereof
  申请人：——

  公开号：US20020082450A1

  公开（公告）日：2002-06-27

  An industrially advantageous method of producing &bgr;-halogeno-&agr;-aminocarboxylic acids is provided. Methods are also provided of producing optically active N-protected-S-phenylcysteines having high optical purity and of intermediates thereof, respectively, in which the above production method is utilized. A method of producing &bgr;-halogeno-&agr;-aminocarboxylic acids or salts thereof is disclosed which comprises halogenating the hydroxyl group of a &bgr;-hydroxy-&agr;-aminocarboxylic acid (in which the basicity of the amino group in &agr;-position is not masked by the presence of a substituent on said amino group) or a salt thereof with an acid with a halogenating agent. A method of producing optically active N-protected-S-phenylcysteines represented by the general formula (3) or salts thereof is further disclosed which comprises applying the above production method to optically active serine or a salt thereof and then carrying out treatment with an amino-protecting agent and reaction with thiophenol under a basic condition. 1

  提供了一种工业上有利的制备&bgr;-卤代-&agr;-氨基羧酸的方法。还提供了制备高光学纯度N-保护-S-苯基半胱氨酸及其中间体的方法，其中利用上述生产方法。揭示了一种制备&bgr;-卤代-&agr;-氨基羧酸或其盐的方法，其包括使用酸和卤代试剂卤代&bgr;-羟基-&agr;-氨基羧酸（其中&agr;-位置的氨基基性未被氨基上的取代基掩盖）或其盐的羟基。还揭示了一种制备由通式（3）表示的光学活性N-保护-S-苯基半胱氨酸或其盐的方法，其包括将上述生产方法应用于光学活性丝氨酸或其盐，并在碱性条件下进行氨基保护剂的处理和与硫苯酚反应。
• Side-Chain Extended Ligation
  申请人：Botti Paolo

  公开号：US20090192300A1

  公开（公告）日：2009-07-30

  The invention is directed to methods and compositions for chemical ligation of a first component that includes a carboxythioester and a second component that includes an amino-functionalized compound bearing a branched side chain that includes a removable thiol auxiliary, to give a ligation product having an amide bond at the ligation site. The reactants of the invention are chemoselective and the thiol moiety is removable from the ligation product. Removal of the thiol can be exploited to generate a native side chain at the ligation site. The methods and compositions of the invention are particularly useful for ligation of peptides and polypeptides. The ligation system of the invention is applicable to a wide variety of molecules, and thus can be exploited to generate peptides, polypeptides and other amino acid containing polymers.

  本发明涉及一种化学连接的方法和组合物，用于将包括羧基硫酯的第一组分和包括带有可移除巯基辅助剂的分支侧链的氨基功能化合物的第二组分进行化学连接，从而在连接位点上形成酰胺键的连接产物。本发明的反应物具有化学选择性，而巯基部分可从连接产物中移除。利用巯基的去除可以在连接位点上生成天然侧链。本发明的方法和组合物特别适用于肽和多肽的连接。本发明的连接系统适用于各种分子，因此可以用于生成肽，多肽和其他含氨基酸的聚合物。
• SUBSTITUTED CYCLOHEXENONES
  申请人：Knopff Oliver

  公开号：US20100274059A1

  公开（公告）日：2010-10-28

  The present invention relates to a method of preparation of an optically active cyclohexenone derivative of Formula (I) OR1R2*R1 and wherein R 1 and R 2 are organic residues.

  本发明涉及一种制备光学活性环己烯酮衍生物的方法，其化学式为(I) OR1R2* R1，其中R1和R2为有机基团。