5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione | 220509-98-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione
• 英文别名: (S)-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)isatin；(S)-5-[1-(2-phenoxymethylpyrrolidinyl)sulfonyl]isatin；5-{[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonyl}-1H-indole-2,3-dione；(S)-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione；5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonyl-1H-indole-2,3-dione
• CAS: 220509-98-8
• 化学式: C₁₉H₁₈N₂O₅S
• 分子量: 386.428
• InChiKey: QKVWMYQCBWNCQH-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione 在 potassium carbonate 、 对甲苯磺酸 作用下， 以 乙醚 、 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 靛红
  参考文献：
  名称：

  ISATIN DERIVATIVES FOR USE AS IN VIVO IMAGING AGENTS

  摘要：

  异吲哚啉-5-磺酰胺衍生物，包括这些衍生物的药物组合物，它们作为分子成像剂的用途，它们用于与凋亡失调相关的疾病或紊乱的诊断或治疗，合成这些衍生物的方法，用于测定caspase活性和凋亡的分子成像方法，以及评估试验物质对caspase活性的治疗效果的方法。

  公开号：

  US20110195024A1
• 作为产物：
  描述：

  L-脯氨醇 在 吡啶 、 sodium hydride 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 反应 46.5h， 生成 5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione
  参考文献：
  名称：

  5-Pyrrolidinylsulfonyl Isatins as a Potential Tool for the Molecular Imaging of Caspases in Apoptosis

  摘要：

  Caspases are the unique enzymes responsible for the execution of the cell death program and may represent an exclusive target for the specific molecular imaging of apoptosis in vivo. 5-Pyrrolidinylsulfonyl isatins represent potent nonpeptidyl caspase inhibitors that may be suitable for the development of caspase binding radioligands ( CBRs). ( S)-5-[ 1-(2-Methoxymethylpyrrolidinyl) sulfonyl] isatin ( 7) served as a lead compound for modification of its N-1-position. Corresponding pairs of N-1-substituted 2-methoxymethyl- and 2-phenoxymethylpyrrolidinyl derivatives were examined in vitro by biochemical caspase inhibition assays. All target compounds possess high in vitro caspase inhibtion potencies in the nanomolar to subnanomolar range for caspase-3 ( K-i = 0.2- 56.1 nM). As shown for compound ( S)-1-( 4-(2-fluoroethoxy) benzyl)-5-[ 1( 2-methoxymethylpyrrolidinyl) sulfonyl] isatin ( 35), the class of N-1-substituted 5-pyrrolidinylsulfonyl isatins competitively inhibits caspase-3. All caspase inhibitors show selectivity for the effector caspases-3 and -7 in vitro. The 2-methoxymethylpyrrolidinyl versions of the isatins appear to possess superior caspase inhibition potencies in cellular apoptosis inhibition assays compared with the 2-phenoxymethylpyrrolidinyl inhibitors.

  DOI：

  10.1021/jm051217c

文献信息

• Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors
  作者：Loghman Firoozpour、Lixin Gao、Setareh Moghimi、Parvin Pasalar、Jamshid Davoodi、Ming-Wei Wang、Zahra Rezaei、Armin Dadgar、Hoda Yahyavi、Massoud Amanlou、Alireza Foroumadi

  DOI：10.1080/14756366.2020.1809388

  日期：2020.1.1

  In this paper, a new series of isatin-sulphonamide based derivatives were designed, synthesised and evaluated as caspase inhibitors. The compounds containing 1-(pyrrolidinyl)sulphonyl and 2-(phenoxymethyl)pyrrolidin-1-yl)sulphonyl substitution at C5 position of isatin core exhibited better results compared to unsubstituted derivatives. According to the results of caspase inhibitory activity, compound

  在本文中，设计，合成和评估了一系列新的基于isatin-sulphonamide的衍生物作为胱天蛋白酶抑制剂。与未取代的衍生物相比，在靛红核的C5位上含有1-（吡咯烷基）磺酰基和2-（苯氧基甲基）吡咯烷-1-基）磺酰基取代的化合物表现出更好的结果。根据caspase抑制活性的结果，与Ac-DEVD-CHO相比，化合物20d在体外显示出对caspase-3和-7的中等抑制活性（IC 50 = 0.016±0.002μM）。在研究的化合物中，鉴定出一些活性抑制剂，IC 50值在2.33–116.91μM之间。化合物20d的活性通过分子建模研究使之合理化，该研究展示了N-苯基乙酰胺取代的额外范德华相互作用以及有效的T形π-π和π-阳离子相互作用。具有良好的半胱天冬酶抑制活性的化合物20d的引入将有助于研究人员寻找更有效的药物。
• Pyrimidoindolones and methods for using same
  申请人：Dollings Jeffrey Paul

  公开号：US20050250798A1

  公开（公告）日：2005-11-10

  Novel pyrimidoindolone compounds are disclosed. Methods of using the pyrimidoindolone compounds and compositions containing the compounds in the treatment and/or prevention of disease and other conditions related to inflammation, neurodegeneration, osteoarthritis and apoptosis are also disclosed.

  揭示了一种新型的嘧啶吲哚酮化合物。还揭示了使用这些嘧啶吲哚酮化合物的方法，以及包含这些化合物的组合物在治疗和/或预防与炎症、神经退行性疾病、骨关节炎和细胞凋亡相关的疾病和其他情况中的应用。
• ISATIN ANALOGUES AND USES THEREFOR
  申请人：Mach Robert H.

  公开号：US20090068105A1

  公开（公告）日：2009-03-12

  Novel isatin analogues, including isatin analogues comprising Michael Acceptors (IMAs) are disclosed. Further disclosed are methods of synthesis of the isatin analogues, and uses of the analogues, including inhibition of caspase-3 and caspase-7, and in vivo imaging of apoptosis by Positron emission tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

  揭示了新颖的吲哚类似物，包括具有Michael受体的吲哚类似物（IMAs）。进一步揭示了吲哚类似物的合成方法，以及类似物的用途，包括抑制caspase-3和caspase-7，以及通过正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）对凋亡进行体内成像。
• [18F]- and [11C]-Labeled N-benzyl-isatin sulfonamide analogues as PET tracers for Apoptosis: synthesis, radiolabeling mechanism, and in vivo imaging study of apoptosis in Fas-treated mice using [11C]WC-98
  作者：Dong Zhou、Wenhua Chu、Delphine L. Chen、Qi Wang、David E. Reichert、Justin Rothfuss、Andre D'Avignon、Michael J. Welch、Robert H. Mach

  DOI：10.1039/b819024k

  日期：——

  The radiolabeled isatin sulfonamide caspase-3 inhibitor, [18F]2 (WC-II-89), is a potential PET radiotracer for noninvasive imaging of apoptosis. The radiolabeling mechanism was studied by 13C NMR, ESI/MS, and computational calculations. It was found that the high electrophilicity of the C3 carbonyl group in the isatin ring, which served as a trap for [18F]fluoride, was responsible for the failure of the radiolabeling via nucleophilic substitution of the mesylate group in 7a by [18F]fluoride. Once treated with a strong base, 7a opened the isatin ring completely to form an isatinate intermediate 16, which lost the ability to trap [18F]fluoride, thereby allowing the displacement of the mesylate group to afford the 18F-labeled isatinate 17. [18F]17 can be converted to isatin [18F]2 efficiently under acidic conditions. The ring-opening and re-closure of the isatin ring under basic and acidic conditions were confirmed by reversed phase HPLC analysis, ESI/MS and 13C NMR studies. Computational studies of model compounds also support the above proposed mechanism. Similarly, the ring-opening and re-closure method was used successfully in the synthesis of the 11C labeled isatin sulfonamide analogue [11C]4 (WC-98). A microPET imaging study using [11C]4 in the Fas liver apoptosis model demonstrated retained activity in the target organ (liver) of the treated mice. Increased caspase-3 activation in the liver was verified by the fluorometric caspase-3 enzyme assay. Therefore, this study provides a useful method for radio-synthesis of isatin derivative radiotracers for PET and SPECT studies, and [11C]4 is a potential PET radiotracer for noninvasive imaging of apoptosis.

  放射性标记的isatin磺酰胺类caspase-3抑制剂[18F]2 (WC-II-89)是一种潜在的PET放射性示踪剂，可用于细胞凋亡的无创成像。研究人员通过 13C NMR、ESI/MS 和计算对其放射性标记机制进行了研究。研究发现，isatin 环中 C3 羰基的亲电性很高，是[18F]氟化物的捕获物，这也是 7a 中的甲磺酸基团被[18F]氟化物亲核取代而导致放射性标记失败的原因。经强碱处理后，7a 完全打开了异汀环，形成了异汀酸酯中间体 16，该中间体失去了捕获[18F]氟化物的能力，从而使间苯二甲酸酯基团发生位移，得到了 18F 标记的异汀酸酯 17。在酸性条件下，[18F]17 可以高效地转化为异汀[18F]2。反相 HPLC 分析、ESI/MS 和 13C NMR 研究证实了在碱性和酸性条件下异atin 环的开环和再闭环。对模型化合物的计算研究也支持上述机制。同样，开环和再闭环法也被成功用于合成 11C 标记的靛红磺酰胺类似物 [11C]4 (WC-98)。在 Fas 肝细胞凋亡模型中使用 [11C]4 进行的 microPET 成像研究表明，经处理的小鼠的靶器官（肝脏）中保留了[11C]4 的活性。肝脏中激活的 Caspase-3 增加通过荧光法 Caspase-3 酶测定得到了验证。因此，这项研究为 PET 和 SPECT 研究提供了一种放射性合成异汀衍生物放射性示踪剂的有用方法，[11C]4 是一种潜在的 PET 放射性示踪剂，可用于细胞凋亡的无创成像。
• [EN] ANTIBACTERIAL AGENTS<br/>[FR] AGENTS ANTIBACTÉRIENS
  申请人：RANBAXY LAB LTD

  公开号：WO2006013409A1

  公开（公告）日：2006-02-09

  The present invention provides acylide derivatives, which can be used as antibacterial agents. Compounds disclosed herein can be used for the treatment or prevention of a condition caused by or contributed to by Gram-positive, Gram-negative or anaerobic bacteria, more particularly against bacterium such as Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., My obacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, B ccillus or Enterobactericeae. Processes for the preparation of disclosed compounds, pharmaceutical compositions thereof, and method of treating bacterial infections, are also provided.

  本发明提供了酰亚胺衍生物，可用作抗菌剂。本文所披露的化合物可用于治疗或预防由革兰氏阳性菌、革兰氏阴性菌或厌氧菌引起或促成的疾病，特别是对于葡萄球菌、链球菌、肠球菌、衣原体、莫拉克斯氏菌属、克拉米多菌属、支原体、军团菌属、分枝杆菌、幽门螺杆菌、梭菌、拟杆菌属或肠杆菌科等细菌尤其有效。同时，本发明还提供了所披露化合物的制备方法、药物组合物以及治疗细菌感染的方法。