1-Methyl-4-methoxy-Δ³-pyrrolin-2-one | 90968-33-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 1-Methyl-4-methoxy-Δ³-pyrrolin-2-one
• 英文别名: 4-methoxy-1-methylpyrrol-2(5H)-one；N-methyl-4-O-methyl tetramate；4-methoxy-1-methyl-1,5-dihydropyrrol-2-one；4-methoxy-1-methyl-2,5-dihydro-1H-pyrrol-2-one；3-methoxy-1-methyl-2H-pyrrol-5-one
• CAS: 90968-33-5
• 化学式: C₆H₉NO₂
• mdl: MFCD12923666
• 分子量: 127.143
• InChiKey: VRQCKEDJWJPNJH-UHFFFAOYSA-N

物化性质

• 熔点：
  125-126.5 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  296.7±39.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 储存条件：
  2-8℃

反应信息

• 作为反应物：
  描述：

  1-Methyl-4-methoxy-Δ³-pyrrolin-2-one 在 硫酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-甲基-2,4-吡咯烷二酮
  参考文献：
  名称：

  Synthesis of 4-alkoxy-Δ3-pyrrolin-2-ones and tetramic acids

  摘要：

  DOI：

  10.1016/s0040-4039(01)90063-2
• 作为产物：
  描述：

  (E)-3-甲氧基-2-丁烯酸甲酯 在 N-溴代丁二酰亚胺(NBS) 作用下， 生成 1-Methyl-4-methoxy-Δ³-pyrrolin-2-one
  参考文献：
  名称：

  Synthesis of 4-alkoxy-Δ3-pyrrolin-2-ones and tetramic acids

  摘要：

  DOI：

  10.1016/s0040-4039(01)90063-2

文献信息

• TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas, Inc.

  公开号：US20180125821A1

  公开（公告）日：2018-05-10

  The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为tau蛋白的调节剂具有实用性。具体而言，本公开涉及含有一端结合到E3泛素连接酶的VHL或cereblon配体，另一端结合到tau蛋白的双功能化合物，使得tau蛋白与泛素连接酶靠近，以实现tau蛋白的降解（和抑制）。本公开展示了与tau蛋白降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由tau蛋白聚集或积累导致的疾病或紊乱。
• [EN] PROTEOLYSIS TARGETING CHIMERIC (PROTAC) COMPOUND WITH E3 UBIQUITIN LIGASE BINDING ACTIVITY AND TARGETING ALPHA-SYNUCLEIN PROTEIN FOR TREATING NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉ CHIMÈRE CIBLANT LA PROTÉOLYSE (PROTAC) AYANT UNE ACTIVITÉ DE LIAISON À L'UBIQUITINE LIGASE E3 ET CIBLANT UNE PROTÉINE ALPHA-SYNUCLÉINE POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2020041331A1

  公开（公告）日：2020-02-27

  The present disclosure relates to bifunctional compounds, which find utility as modulators of alpha-synuclein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/ inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure. Such diseases or disorders are alpha-synucleinopathies or neurodegenerative diseases associated with alpha-synuclein accumulation and aggregation, such as e.g. Parkinson Disease, Alzheimer's Disease, dementia, dementia with Lewy bodies or multiple system atrophy, in particular Parkinson's Disease.

  本公开涉及双功能化合物，其作为α-突触核蛋白（目标蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端为Von Hippel-Lindau、cereblon、凋亡抑制蛋白或鼠双分子同源物2配体的双功能化合物，该配体与相应的E3泛素连接酶结合，另一端为与目标蛋白结合的基团，使得目标蛋白靠近泛素连接酶以促使目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/抑制相关的广泛药理活性范围。本公开的化合物和组合物用于治疗或预防由目标蛋白聚集或积累导致的疾病或紊乱。这些疾病或紊乱是与α-突触核蛋白积累和聚集相关的α-突触核蛋白病或神经退行性疾病，例如帕金森病、阿尔茨海默病、痴呆症、带有Lewy小体的痴呆症或多系统萎缩，特别是帕金森病。
• [EN] MODULATORS OF ESTROGEN RECEPTOR PROTEOLYSIS AND ASSOCIATED METHODS OF USE<br/>[FR] MODULATEURS DU RÉCEPTEUR DES ŒSTROGÈNES DE PROTÉOLYSE ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：ARVINAS INC

  公开号：WO2018140809A1

  公开（公告）日：2018-08-02

  The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a cereblon, Von Hippel-Lindau ligase-binding moiety, Inhibitors of Apotosis Proteins, or mouse double-minute homolog 2 ligand, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为雌激素受体（靶蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端为 cereblon、Von Hippel-Lindau 配体结合基团、凋亡抑制蛋白或鼠双分子同源物 2 配体的双功能化合物，该化合物与相应的 E3 泛素连接酶结合，并且另一端含有结合靶蛋白的基团，使得靶蛋白与泛素连接酶靠近，以实现对靶蛋白的降解（和抑制）。本公开展示了与靶蛋白的降解/抑制相关的广泛药理活性范围。本公开的化合物和组合物用于治疗或预防由靶蛋白聚集或积累导致的疾病或紊乱。
• [EN] BIFUNCTIONAL MOLECULES CONTAINING AN E3 UBIQUITINE LIGASE BINDING MOIETY LINKED TO A BCL6 TARGETING MOIETY<br/>[FR] MOLÉCULES BIFONCTIONNELLES CONTENANT UNE FRACTION DE LIAISON À L'UBIQUITINE LIGASE E3 LIÉE À UNE FRACTION CIBLANT BCL6
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2021077010A1

  公开（公告）日：2021-04-22

  Bifunctional compounds, which find utility as modulators of B-cell lymphoma 6 protein (BCL6; target protein), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand that binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本发明描述了双功能化合物，其作为B细胞淋巴瘤6蛋白（BCL6；靶蛋白）的调节剂。特别是，本发明中的双功能化合物一端含有与相应的E3泛素连接酶结合的Von Hippel-Lindau、cereblon、凋亡蛋白抑制剂或小鼠双分钟同源蛋白2的配体，另一端含有与靶蛋白结合的部分，使得靶蛋白被置于泛素连接酶附近，以促进靶蛋白的降解（和抑制）。本发明中的双功能化合物展示了与靶蛋白降解/抑制相关的广泛药理活性。可以通过本发明中的化合物和组合物治疗或预防由靶蛋白聚集或积累引起的疾病或失调。
• The synthesis of 5-ylidenepyrrol-2(5H)-ones from maleimides and from pyrrol-2-(5H)-ones
  作者：G. Bryon Gill、Gwyn D. James、Karen V. Oates、Gerald Pattenden

  DOI：10.1039/p19930002567

  日期：——

  However, the lithium enolate of methyl trimethylsilylacetate (or other Peterson-type reagents) underwent successful addition to N-methylmaleimides at –78 °C; the 5-ylidenepyrrolone product distributions were similar to those obtained with the stabilised phosphoranes. Variation of the 5-alkylidene side-chain was achieved through the reactions of N-methylmaleimides with alkyl Grignard reagents by dehydrating-the

  通过使合适的马来酸酐与乙酸铵或乙酸甲基铵在沸腾的乙酸中反应制备了一系列的马来酰亚胺5。在中等强迫条件下，马来酰亚胺与稳定的ane烷进行维蒂希型反应，得到5-亚吡咯2（5 H）-ones 6。反应的容易程度和向不对称马来酰亚胺中添加的区域化学取决于3-取代基的性质以及是否存在N-烷基取代基。因此，3-甲氧基马来酰亚胺仅在C-2处反应；N的存在-甲基取代基需要使用更多的强迫反应条件，但不会改变对C-2攻击的偏爱。然而，对于3-甲基马来酰亚胺，如5d中那样，由于存在N-甲基取代基而推翻了在5c中C-2反应的轻微偏好。不稳定的phosphor烷或氧化膦的相关反应通常只能提供难处理的树胶，而使用Julia型试剂只能回收原料。但是，三甲基甲硅烷基乙酸甲酯的烯醇锂（或其他Peterson型试剂）已成功添加到N中。-甲基马来酰亚胺––78°C；5-亚甲基吡咯烷酮产物的分布类似于用稳定的膦烷获得的分布。通过