(S)-tert-butyl (4-(methylthio)-1-oxo-1-(pyrrolidin-1-yl)butan-2-yl)carbamate | 485835-59-4

• 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: (S)-tert-butyl (4-(methylthio)-1-oxo-1-(pyrrolidin-1-yl)butan-2-yl)carbamate
• 英文别名: BOC-L-methionyl-pyrrolidine；tert-butyl N-[(2S)-4-methylsulfanyl-1-oxo-1-pyrrolidin-1-ylbutan-2-yl]carbamate
• CAS: 485835-59-4
• 化学式: C₁₄H₂₆N₂O₃S
• 分子量: 302.438
• InChiKey: JWBJCYYIZPFBIO-NSHDSACASA-N

物化性质

• 沸点：
  473.1±40.0 °C(Predicted)
• 密度：
  1.121±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl (4-(methylthio)-1-oxo-1-(pyrrolidin-1-yl)butan-2-yl)carbamate 在 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 17.0h， 生成 (S)-1-(4-aminobenzyl)-3-(4-(methylthio)-1-oxo-1-(pyrrolidin-1-yl)butan-2-yl)urea
  参考文献：
  名称：

  Cyclophilin D的小分子抑制剂可保护线粒体功能，作为急性胰腺炎的潜在治疗方法

  摘要：

  线粒体通透性过渡孔（MPTP）的打开会导致急性胰腺炎（AP）中的线粒体功能障碍和坏死，这种情况没有经过专门的药物治疗。亲环蛋白D（CypD）是一种线粒体基质肽基-脯氨酰异构酶，可调节MPTP，并且是AP的药物靶标。我们已经合成了基于尿素的亲环蛋白小分子抑制剂，并使用结合和异构酶活性测定法针对CypD进行了测试。CypD /抑制剂相互作用的热力学曲线通过等温滴定量热法测定。获得了七个新的CypD-抑制剂复合物高分辨率晶体结构，以指导化合物的优化。化合物4，13，14，和19在新鲜分离的鼠胰腺腺泡细胞（PACS）进行测试，以确定细胞线粒体膜电位的毒素引起的损耗（ΔΨ的抑制米）和坏死性细胞死亡途径的激活。化合物19被发现具有A K d为410nm和有利的热力学轮廓，它显示的ΔΨ显著保护米和减少鼠的坏死以及人的PAC。化合物19对于未来的潜在客户优化具有重大前景。

  DOI：

  10.1021/acs.jmedchem.5b01801
• 作为产物：
  描述：

  Boc-L-蛋氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 (S)-tert-butyl (4-(methylthio)-1-oxo-1-(pyrrolidin-1-yl)butan-2-yl)carbamate
  参考文献：
  名称：

  New Prolyl Oligopeptidase Inhibitors Developed from Dicarboxylic Acid Bis(l-prolyl-pyrrolidine) Amides

  摘要：

  Isophthalic acid bis(L-prolyl-pyrrolidine) amide is a very potent prolyl oligopeptidase inhibitor, but it has a log P value of -0.2, which is very low for a compound targeted to the brain. Therefore, these types of compounds were further modified to improve the structure-activity relationships, with the focus on increasing the log P value. The inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. The most promising compounds resulted from replacing the pyrrolidinyl. group at the P5 site by cycloalkyl groups, such as cyclopentyl and cyclohexyl groups, and by a phenyl group. These compounds are slightly more potent, and they have a significantly higher log P value. The potency of these compounds was further increased by replacing the pyrrolidinyl group at the P1 site by 2(S)-cyanopyrrolidinyl and 2(S)(hydroxyacetyl)pyrrolidinyl groups.

  DOI：

  10.1021/jm030811o

文献信息

• Water Compatible Photoarylation of Amino Acids and Peptides
  作者：Alex Sudakow、Uli Papke、Thomas Lindel

  DOI：10.1002/chem.201402959

  日期：2014.8.11

  A novel photoarylation of amino acids and peptides is described, which tolerates the presence of water. Irradiation of Boc‐protected amino acids in the presence of N‐protected 2‐azidobenzimidazoles leads to selective arylation of carboxy termini or side chains. The new reaction also works for peptides. Irradiation of the nonapeptide H‐SPSYVYHQF‐OH also resulted in selective arylation of the tyrosine

  描述了氨基酸和肽的新型光芳基化，其容许水的存在。在N保护的2-叠氮基苯并咪唑类化合物的存在下照射Boc保护的氨基酸会导致羧基末端或侧链的选择性芳基化。新反应也适用于肽。如ESI-MS / MS片段所示，辐照九肽H-SPSYVYHQF-OH还导致酪氨酸侧链选择性芳基化。化学和区域选择性可能将标题反应添加到光亲和标记方法库中。
• [EN] COMPOUNDS HAVING PROLYL OLIGOPEPTIDASE INHIBITORY ACTIVITY, METHODS FOR THEIR PREPARATION AND THEIR USE<br/>[FR] COMPOSES INHIBITEURS DE LA PROLYL OLIGOPEPTIDASE, PROCEDES DE PREPARATION ET UTILISATION
  申请人：ORION CORP

  公开号：WO2003004468A1

  公开（公告）日：2003-01-16

  Compounds of the formula (I), wherein the symbol aa means a residue of an α-amino acid. The invention is also directed to a method for the preparation of the compounds of formula (I), as well as their use as prolyl oligopeptide inhibitors, for example for the treatment of Alzheimer's disease.

  公式（I）的化合物，其中符号aa表示α-氨基酸的残基。本发明还涉及一种制备公式（I）化合物的方法，以及它们作为脯氨酰寡肽抑制剂的用途，例如用于治疗阿尔茨海默病。
• Compounds having prolyl oligopeptidase inhibitory activity, methods for their preparation and their use
  申请人：Gynther Jukka

  公开号：US20050020677A1

  公开（公告）日：2005-01-27

  Compounds of the formula (I), wherein the symbol aa means a residue of an α-amino acid. The invention is also directed to a method for the preparation of the compounds of formula (I), as well as their use as prolyl oligopeptide inhibitors, for example for the treatment of Alzheimer's disease.

  式(I)的化合物，其中符号aa表示α-氨基酸残基。本发明还涉及一种制备式(I)化合物的方法，以及它们作为脯氨酰寡肽酶抑制剂的用途，例如用于治疗阿尔茨海默病。
• COMPOUNDS HAVING PROLYL OLIGOPEPTIDASE INHIBITORY ACTIVITY, METHODS FOR THEIR PREPARATION AND THEIR USE
  申请人：ORION CORPORATION

  公开号：EP1401810A1

  公开（公告）日：2004-03-31
• US7173024B2
  申请人：——

  公开号：US7173024B2

  公开（公告）日：2007-02-06