tert-butyl (4-hydroxy-2-methoxyphenyl)carbamate | 1435933-04-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl (4-hydroxy-2-methoxyphenyl)carbamate
• 英文别名: Tert-butyl 4-hydroxy-2-methoxyphenylcarbamate；tert-butyl N-(4-hydroxy-2-methoxyphenyl)carbamate
• CAS: 1435933-04-2
• 化学式: C₁₂H₁₇NO₄
• 分子量: 239.271
• InChiKey: UUWWYFQJCAFFSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-hydroxy-2-methoxyphenyl)carbamate 在 palladium 10% on activated carbon 、 氢气 、 三苯基膦 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 甲醇 、 甲苯 为溶剂， 生成 tert-butyl (2-methoxy-4-(piperidin-4-yloxy)phenyl)carbamate
  参考文献：
  名称：

  AMINOPYRIMIDINYL DERIVATIVES FOR THE TREAMENT OF PARKINSON'S DISEASE

  摘要：

  公开了一类异双功能化合物，这些化合物能够诱导亮氨酸富集重复激酶2（LRRK2）和磷酸二酯酶6D（PDE6D）的降解。这些化合物的一端可与LRRK2结合，另一端能够与泛素E3连接酶（例如小脑蛋白、冯·希佩尔-林道蛋白或细胞凋亡抑制蛋白（clAP））结合，从而将LRRK2与E3连接酶置于邻近位置，诱导LRRK2蛋白的泛素化和降解。本文还公开了一种包含这些异双功能化合物的药物组合物，以及利用这些化合物治疗与LRRK2和PDE6D相关的疾病和障碍的方法。

  公开号：

  EP4276097A1
• 作为产物：
  描述：

  3-甲氧基-4-硝基苯酚 在 吡啶 、 palladium on activated charcoal 、 氢气 、 碳酸氢钠 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 63.0h， 生成 tert-butyl (4-hydroxy-2-methoxyphenyl)carbamate
  参考文献：
  名称：

  The carbonate analogues of 5′-halogenated resiniferatoxin as TRPV1 ligands

  摘要：

  A series of carbonate analogues of 5'-halogenated RTX have been investigated in order to examine the effect of the carbonate group as a linker and the role of halogens in the reversal of activity from agonism to antagonism for rat and human TRPV1 heterologously expressed in Chinese hamster ovary cells. The carbonate analogues showed similar activities to the corresponding RTX derivatives in rat TRPV1 but lower potency in human TRPV1. 5-Halogenation converted the agonists to partial agonists or full antagonists and the extent of antagonism reflected the order of I > Br > Cl > F, with a somewhat greater extent of antagonism for the derivatives of the 4-amino RTX surrogates compared to the corresponding derivatives of RTX itself. The carbonate analogues of I-RTX: (60) and 5-bromo-4-amino-RTX (66) were potent and full antagonists with K-i(ant) = 2.23 and 2.46 nM, respectively, for rat TRPV1, which were ca. 5-fold more potent than I-RTX (2) under our conditions. The conformational analysis of the I-RTX-carbonate (60) indicated that its bent conformation was similar to that of I-RTX, consistent with compound 60 and I-RTX showing comparable potent antagonism. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.07.042

文献信息

• [EN] POLYAROMATIC UREA DERIVATIVES AND THEIR USE IN THE TREATMENT OF MUSCLE DISEASES<br/>[FR] DÉRIVÉS D'URÉE POLYAROMATIQUES ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES MUSCULAIRES
  申请人：ANAGENESIS BIOTECHNOLOGIES S A S

  公开号：WO2021013712A1

  公开（公告）日：2021-01-28

  The current invention provides urea derivatives, in particular compounds having the core structure heteroaryl-NH-CO-NH-aryl-O- heteroaryl, for use in treating, ameliorating, delaying, curing and/ or preventing a disease or condition associated with muscle cells and/or satellite cells, such as Duchenne muscular dystrophy, Becker muscular dystrophy, cachexia or sarcopenia.

  当前的发明提供尿素衍生物，特别是具有核心结构杂环基-NH-CO-NH-芳基-O-杂环基的化合物，用于治疗、改善、延缓、治愈和/或预防与肌肉细胞和/或卫星细胞相关的疾病或症状，如杜兴氏肌肉萎缩症、贝克氏肌肉萎缩症、虚弱或肌肉萎缩症。
• Diphenyl ether derivatives occupy the expanded binding site of cyclohexanedione compounds at the colchicine site in tubulin by movement of the αT5 loop
  作者：Oskia Bueno、Marta Gargantilla、Juan Estévez-Gallego、Solange Martins、J. Fernando Díaz、María-José Camarasa、Sandra Liekens、María-Jesús Pérez-Pérez、Eva-María Priego

  DOI：10.1016/j.ejmech.2019.03.045

  日期：2019.6

  complex has revealed a conformational change in the αT5 loop. By a grid-based computational analysis of the tubulin-DAMA-colchicine binding site, we have identified a new favourable binding area in the colchicine-site that was unexplored by our lead TUB075. Thus, based on a structure-guided design, new cyclohexanedione derivatives have been synthesized and tested for tubulin binding and in cellular assays

  微管靶向剂代表了抗癌剂开发中非常活跃的舞台。特别地，正在深入研究在微管蛋白中的秋水仙碱位点结合的化合物，并且最近在该结合位点上可获得的结构信息允许新配体的结构定向设计。我们最近报道的与微管蛋白和微管蛋白-DAMA-秋水仙碱复合物结合的环己二酮衍生物TUB075的高分辨率X射线结构的结构比较显示了αT5环的构象变化。通过微管蛋白-DAMA-秋水仙碱结合位点的基于网格的计算分析，我们在秋水仙碱位点中发现了一个新的有利结合区，而我们的前导TUB075尚未对此进行探索。因此，根据结构指导设计，已经合成了新的环己二酮衍生物，并进行了微管蛋白结合和细胞分析测试。结果，我们确定了具有IC的二苯醚衍生物针对三种不同的肿瘤细胞系，大约10–40 nM处的50值和与秋水仙碱相似的微管蛋白亲和常数大约在10 7  M -1附近。如预期的那样，他们以低至0.08μM的浓度停止了G2 / M期的细胞周期进程。
• Discovery of XL01126: A Potent, Fast, Cooperative, Selective, Orally Bioavailable, and Blood–Brain Barrier Penetrant PROTAC Degrader of Leucine-Rich Repeat Kinase 2
  作者：Xingui Liu、Alexia F. Kalogeropulou、Sofia Domingos、Nikolai Makukhin、Raja S. Nirujogi、Francois Singh、Natalia Shpiro、Anton Saalfrank、Esther Sammler、Ian G. Ganley、Rui Moreira、Dario R. Alessi、Alessio Ciulli

  DOI：10.1021/jacs.2c05499

  日期：2022.9.21

  compensates for a substantial loss of binary binding affinities to VHL and LRRK2, underscoring its strong degradation performance in cells. Remarkably, XL01126 is orally bioavailable (F = 15%) and can penetrate the blood–brain barrier after either oral or parenteral dosing in mice. Taken together, these experiments qualify XL01126 as a suitable degrader probe to study the noncatalytic and scaffolding functions

  富含亮氨酸重复激酶 2 (LRRK2) 是帕金森病最有希望的靶点之一。 LRRK2 靶向策略主要集中于 1 型激酶抑制剂，但其具有局限性，因为受抑制的蛋白质会干扰自然机制，从而可能导致不良副作用。在此，我们报告了 LRRK2 蛋白水解靶向嵌合体 (PROTAC) 的开发，最终发现了降解剂 XL01126，作为替代 LRRK2 靶向策略。基于 E3 连接酶 von Hippel-Lindau (VHL)、Cereblon (CRBN) 和细胞凋亡抑制剂 (cIAP) 配体的 PROTAC 的初步设计和筛选确定了含有硫醚缀合的 VHL 配体 VH101 的最佳降解剂。第二轮药物化学探索使 XL01126 成为多种细胞系中 LRRK2 的快速有效降解剂，其 DC 50值在 15-72 nM 范围内， D最大值范围在 82% 至 90% 之间，降解半衰期跨越0.6 至 2.4 小时。 XL01126
• COMBINATION OF POLYAROMATIC UREA DERIVATIVES AND GLUCOCORTICOID OR HDAC INHIBITOR FOR THE TREATMENT OF DISEASES OR CONDITIONS ASSOCIATED WITH MUSCLE CELLS AND/OR SATELLITE CELLS
  申请人：Anagenesis Biotechnologies

  公开号：EP4029501A1

  公开（公告）日：2022-07-20

  The current invention provides compounds for treating, ameliorating, delaying, curing and/or preventing a disease or condition associated with muscle cells and/or satellite cells, such as Duchenne muscular dystrophy, Becker muscular dystrophy, cachexia or sarcopenia, in combination with a corticosteroid or a HDAC inhibitor.

  本发明提供了一种与皮质类固醇或HDAC抑制剂联合使用的化合物，用于治疗、改善、延缓、治愈和/或预防与肌肉细胞和/或卫星细胞相关的疾病或病症，如杜氏肌萎缩症、贝克肌萎缩症、消瘦或肌肉萎缩症。
• [EN] CCR2 INHIBITORS<br/>[FR] INHIBITEURS DE CCR2
  申请人：[en]ARTICA THERAPEUTICS B.V.

  公开号：WO2023031308A1

  公开（公告）日：2023-03-09

  The present invention relates to novel substituted aryl sulfonamide compounds, to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of substituted aryl sulfonamide compounds according to formula (I) in the treatment of CC Chemokine Receptor 2 (CCR2) mediated disorders, e.g. cancer.