2-(苯氧基甲基)吡咯烷-1-羧酸-(S)-叔丁酯 | 174213-51-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 2-(苯氧基甲基)吡咯烷-1-羧酸-(S)-叔丁酯
• 英文名称: (S)-tert-butyl 2-(phenoxymethyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (S)-2-(phenoxymethyl)pyrrolidine-1-carboxylate；(S)-N-Boc-2-(phenoxymethyl)pyrrolidine；(S)-1-BOC-2-(phenoxymethyl)pyrrolidine；N-t-Butoxycarbonyl-2(S)-phenoxymethylpyrrolidine；(S)-2-phenoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester；tert-butyl (2S)-2-(phenoxymethyl)pyrrolidine-1-carboxylate
• CAS: 174213-51-5
• 化学式: C₁₆H₂₃NO₃
• 分子量: 277.364
• InChiKey: HNDZHKHZJFMDRO-ZDUSSCGKSA-N

物化性质

• 沸点：
  373.7±15.0 °C(Predicted)
• 密度：
  1.081±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-(苯氧基甲基)吡咯烷-1-羧酸-(S)-叔丁酯 在 sodium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 (S)-1-[4-(2-bromoethoxy)-benzyl]-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione
  参考文献：
  名称：

  Synthesis, radiolabeling, and in vivo evaluation of an 18F-labeled isatin analog for imaging caspase-3 activation in apoptosis

  摘要：

  A non-peptide-based isatin sulfonamide analog, WC-II-89, was synthesized and its inhibition toward recombinant human caspase-3 and other caspases was determined. This compound showed high potency for inhibiting caspase-3 and -7, and high selectivity against caspases-1, -6, and -8. [F-18]WC-II-89 was synthesized via a nucleophilic substitution of the corresponding mesylate precursor in high yield and radiochemical purity. Biodistribution studies using [F-18]WC-II-89 revealed higher uptake in liver and spleen of cycloheximide-treated rats, an animal model of apoptosis, relative to control animals. Western blot analysis confirmed the presence of activated caspase-3 in the liver and spleen of cycloheximide-treated animals. MicroPET imaging studies revealed a high uptake of the radiotracer in the liver of a cycloheximide-treated rat relative to the untreated control. These data suggest that [F-18]WC-II-89 is a potential radiotracer for imaging caspase-3 activation in tissues undergoing apoptosis. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.045
• 作为产物：
  描述：

  L-脯氨醇 在 吡啶 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 44.5h， 生成 2-(苯氧基甲基)吡咯烷-1-羧酸-(S)-叔丁酯
  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。
• Inhibitors of protein isoprenyl transferases
  申请人：Abbott Laboratories

  公开号：US06277871B1

  公开（公告）日：2001-08-21

  The present invention relates to novel compounds of Formula I which are useful in inhibiting protein isoprenyl transferases and the farnesylation or geranylgeranylation of the oncogene protein Ras and other related small g-proteins, and compositions containing such compounds and methods of using such compounds.

  本发明涉及一种新型化合物，其化学式为I，可用于抑制蛋白异戊二烯基转移酶以及致癌基因蛋白Ras和其他相关小G蛋白的法尼醇化或杜鲁醇化，以及含有这种化合物的组合物和使用这种化合物的方法。
• [EN] AMIDO-THIOPHENE COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS AMIDO-THIOPHÈNE ET LEUR UTILISATION
  申请人：UNIV EDINBURGH

  公开号：WO2009112845A1

  公开（公告）日：2009-09-17

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain amido-thiophene compounds that, inter alia, inhibit 11 β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1 ). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11 β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11 β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.

  本发明一般涉及治疗化合物领域。更具体地，本发明涉及某些酰胺-噻吩化合物，其中包括抑制11β-羟基类固醇脱氢酶1（11β-HSD1）的作用。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物和组合物，在体内和体外，抑制11β-羟基类固醇脱氢酶1；治疗通过抑制11β-羟基类固醇脱氢酶1而得到改善的疾病；治疗代谢综合征，其中包括糖尿病和肥胖等疾病，以及相关疾病，包括胰岛素抵抗、高血压、脂质紊乱和心血管疾病，如缺血性（冠状）心脏病；治疗中枢神经系统疾病，如轻度认知障碍和早期痴呆，包括阿尔茨海默病等。
• 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。
• Caspases and apoptosis
  申请人：SmithKline Beecham Corporation

  公开号：US06514992B1

  公开（公告）日：2003-02-04

  The present invention is to novel compounds of Formula (I), their pharmaceutical compositions, and to the novel inhibition of Caspases for use in the treatment of apoptosis, and disease states caused by excessive or inappropriate cell death.

  本发明涉及式（I）的新化合物，它们的药物组合物，以及用于治疗凋亡和由过度或不恰当的细胞死亡引起的疾病状态的新的Caspases抑制方法。