methyl (S)-1-(2-methoxy-2-oxoacetyl)piperidine-2-carboxylate | 124093-26-1

• 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: methyl (S)-1-(2-methoxy-2-oxoacetyl)piperidine-2-carboxylate
• 英文别名: (S)-1-methoxyoxalyl-piperidine-2-carboxylic acid methyl ester；methyl (2S)-1-(2-methoxy-2-oxoacetyl)piperidine-2-carboxylate
• CAS: 124093-26-1
• 化学式: C₁₀H₁₅NO₅
• 分子量: 229.233
• InChiKey: STHCNBCZTGUTTE-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (S)-1-(2-methoxy-2-oxoacetyl)piperidine-2-carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 (S)-1-(3,3-二甲基-2-氧戊烷酰基)哌啶-2-羧酸
  参考文献：
  名称：

  靶向共价抑制疟原虫FK506结合蛋白35

  摘要：

  FK506结合蛋白35，FKBP35，已被认为是必需的疟疾酶。雷帕霉素和FK506在培养的寄生虫中表现出抗疟原虫活性。然而，由于FKBP的结合口袋的高度保守的性质和这些药物的免疫抑制特性，需要选择性地抑制FKBP35并且缺乏不良副作用的化合物。与人FKBP相比，FKBP35在雷帕霉素结合口袋附近包含一个半胱氨酸C106，为开发靶向疟原虫FKBP35的共价抑制剂提供了机会。在这里，我们合成了FKBP35的抑制剂，表明它们在模型细胞环境中直接结合FKBP35，选择性地共价修饰C106，并在血阶段培养的寄生虫中表现出抗疟原虫活性。

  DOI：

  10.1021/acsmedchemlett.0c00272
• 作为产物：
  描述：

  甲基戊酰氯 、 H-高脯氨酸-OMe盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以81%的产率得到methyl (S)-1-(2-methoxy-2-oxoacetyl)piperidine-2-carboxylate
  参考文献：
  名称：

  靶向共价抑制疟原虫FK506结合蛋白35

  摘要：

  FK506结合蛋白35，FKBP35，已被认为是必需的疟疾酶。雷帕霉素和FK506在培养的寄生虫中表现出抗疟原虫活性。然而，由于FKBP的结合口袋的高度保守的性质和这些药物的免疫抑制特性，需要选择性地抑制FKBP35并且缺乏不良副作用的化合物。与人FKBP相比，FKBP35在雷帕霉素结合口袋附近包含一个半胱氨酸C106，为开发靶向疟原虫FKBP35的共价抑制剂提供了机会。在这里，我们合成了FKBP35的抑制剂，表明它们在模型细胞环境中直接结合FKBP35，选择性地共价修饰C106，并在血阶段培养的寄生虫中表现出抗疟原虫活性。

  DOI：

  10.1021/acsmedchemlett.0c00272

文献信息

• Small Molecules for Imaging Protein-Protein Interactions
  申请人：Li C. King

  公开号：US20080085238A1

  公开（公告）日：2008-04-10

  A tissue is imaged to detect the presence of amyloid deposits or other target proteins prior to their aggregation into plaques, with the assistance of the administration of a labeled bifunctional compound of which one functionality binds to the target protein and the second functionality binds to a chaperone protein that is present in the tissue of interest. The two functionalities have different binding affinities, the target-binding functionality having the greater binding affinity, with the result that the bifunctional compound preferentially remains in the tissue when bound to the chaperone and then the target protein while bifunctional compound that is not bound to the target protein will leave the tissue. The inclusion of the chaperone allows the imaging process to detect the non-aggregated proteins by way of the label and the difference in kinetics of the binding to the chaperone and the target protein permits one to distinguish between binding of the bifunctional molecule to the chaperone only and binding to the chaperone and then to the target protein. Certain intermediates toward the synthesis of these bifunctional compounds are novel by themselves, and labeled bifunctional molecules in general that utilize a lysine linker are also disclosed as a novel class of compounds.

  一种组织被成像以检测淀粉样沉积物或其他靶蛋白质在聚集成斑块之前的存在，辅助使用一种带标记的双功能化合物的管理，其中一个功能性结合到靶蛋白质，第二个功能性结合到存在于感兴趣组织中的分子伴侣蛋白。这两种功能性具有不同的结合亲和力，结合到靶蛋白质的功能性具有更强的结合亲和力，结果是双功能化合物在与分子伴侣和靶蛋白质结合时更倾向于留在组织中，而未与靶蛋白质结合的双功能化合物会离开组织。包括分子伴侣可以使成像过程通过标记和结合到分子伴侣和靶蛋白质的结合动力学差异来检测非聚集的蛋白质，从而使人们能够区分双功能分子仅与分子伴侣结合和先与分子伴侣结合然后与靶蛋白质结合之间的区别。这些双功能化合物的合成中间体本身是新颖的，同时也公开了一种利用赖氨酸连接物的带标记双功能分子作为一种新颖类化合物。
• Synthesis of <i>N</i>-Glyoxyl Prolyl and Pipecolyl Amides and Thioesters and Evaluation of Their In Vitro and In Vivo Nerve Regenerative Effects
  作者：Gregory S. Hamilton、Yong-Qian Wu、David C. Limburg、Douglas E. Wilkinson、Mark J. Vaal、Jia-He Li、Christine Thomas、Wei Huang、Hansjorg Sauer、Douglas T. Ross、Raj Soni、Yi Chen、Hongshi Guo、Pamela Howorth、Heather Valentine、Shi Liang、Dawn Spicer、Mike Fuller、Joseph P. Steiner

  DOI：10.1021/jm010556c

  日期：2002.8.1

  The recent discovery that small molecule ligands for the peptidyl-prolyl isomerase (PPIase) FKBP12 possess powerful neuroprotective and neuroregenerative properties in vitro and in vivo suggests therapeutic utility for such compounds in neurodegenerative disease. The neurotrophic effects of these compounds are independent of the immunosuppressive pathways by which drugs such as FK506 and rapamycin operate. Previous work by ourselves and other groups exploring the structure-activity relationships (SAR) of small molecules that mimic only the FKBP binding domain portion of FK506 has focused on esters of proline and pipecolic acid. We have explored amide and thioester analogues of these earlier structures and found that they too are extremely potent in promoting recovery of lesioned dopaminergic pathways in a mouse model of Parkinson's disease. Several compounds were shown to be highly effective upon oral administration after lesioning of the dopaminergic pathway, providing further evidence of the potential clinical utility of a variety of structural classes of FKBP12 ligands.
• Orthogonal chemical inducer of dimerization
  申请人：Cornish Virginia W.

  公开号：US20090162858A1

  公开（公告）日：2009-06-25

  A method for identifying a molecule as being able to bind a protein target in a cell, comprising (a) covalently bonding the molecule to trimethoprim (TMP) to form a screening molecule, (b) introducing the screening molecule into the cell which (A) expresses (i) a first fusion protein comprising a binding domain capable of binding TMP, and (ii) a second fusion protein comprising the protein target, and (B) comprises a reporter gene, wherein one of the fusion proteins comprises a DNA-binding domain and the other fusion protein comprises a transcription activation domain and wherein expression of the reporter gene is conditioned on the proximity of the DNA-binding domain to the transcription activation domain; and (c) determining whether the screening molecule binds to the first fusion protein and to the second fusion protein by determining whether the cell expresses the reporter gene, wherein expression of the reporter gene indicates that the molecule binds the protein target and wherein lack of expression of the reporter gene indicates that the molecule does not bind the protein target.
• US6316405B1
  申请人：——

  公开号：US6316405B1

  公开（公告）日：2001-11-13
• US7943775B2
  申请人：——

  公开号：US7943775B2

  公开（公告）日：2011-05-17