tert-butyl 4-(4-chloro-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)piperidine-1-carboxylate | 783368-09-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: tert-butyl 4-(4-chloro-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-(4-chloro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1-carboxylate；tert-butyl 4-(4-chloro-2-oxo-3H-benzimidazol-1-yl)piperidine-1-carboxylate
• CAS: 783368-09-2
• 化学式: C₁₇H₂₂ClN₃O₃
• 分子量: 351.833
• InChiKey: HYABFERSBBBURW-UHFFFAOYSA-N

物化性质

• 密度：
  1.291±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-chloro-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)piperidine-1-carboxylate 在 titanium(IV) isopropylate 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 24.5h， 生成 4-chloro-1-(1-(4-bromo-2-fluorobenzyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one mesylate salt
  参考文献：
  名称：

  Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias

  摘要：

  While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal beta arrestin-mediated signaling because MOR agonist-treated beta arrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents. We recently showed that, within a chemical series, the degree of bias correlates linearly with the magnitude of the respiratory safety index. Herein we describe the synthesis and optimization of piperidine benzimidazolone MOR agonists that together display a wide range of bias (G/beta arr2). We identify structural features affecting potency and maximizing bias and show that many compounds have desirable properties, such as long half-lives and high brain penetration.

  DOI：

  10.1021/acs.jmedchem.8b01136
• 作为产物：
  描述：

  2-氯-6-氟硝基苯 在 sodium tetrahydroborate 、 N,N-二异丙基乙胺 、 nickel dichloride 作用下， 以 二氯甲烷 、 水 、 异丙醇 、 乙腈 为溶剂， 生成 tert-butyl 4-(4-chloro-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  N-哌啶基-苯并咪唑酮衍生物作为 8-氧代-鸟嘌呤 DNA 糖基化酶 1 强效选择性抑制剂的优化

  摘要：

  8-氧代鸟嘌呤 DNA 糖基化酶 1 (OGG1) 从 DNA 中切除氧化鸟嘌呤。除了在基因组完整性维护中的这一作用外，该酶还参与转录过程并作为抑制炎症的靶标。OGG1 的药理学调节极大地有助于理解 bas 切除修复的潜在功能。在这里，我们报告了导致广泛使用的工具化合物 TH5487 的发现和化学优化。

  DOI：

  10.1002/cmdc.202200310

文献信息

• Benzodiazepine cgrp receptor antagonists
  申请人：Burgey S. Christopher

  公开号：US20060148790A1

  公开（公告）日：2006-07-06

  The present invention is directed to compounds of Formula I: (where variables R 1 , R 2 , R 3 , R 6 , R 7 , G, J, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及化合物I的公式：（其中变量R1，R2，R3，R6，R7，G，J，W，X和Y的定义如本文所述），用作CGRP受体拮抗剂，并用于治疗或预防CGRP参与的疾病，例如头痛，偏头痛和群头痛。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗CGRP参与的这些疾病中使用这些化合物和组合物的用途。
• Cgrp receptor antagonists
  申请人：Burgey S. Christopher

  公开号：US20060194783A1

  公开（公告）日：2006-08-31

  The present invention is directed to compounds of Formula I and Formula II: (where variables R1, R2, R3, R4, R6, A, B, G, J, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及式I和式II的化合物：（其中变量R1、R2、R3、R4、R6、A、B、G、J、W、X和Y如本文所定义），其作为CGRP受体拮抗剂在治疗或预防涉及CGRP的疾病，例如头痛、偏头痛和群发性头痛中有用。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗涉及CGRP的这些疾病中使用这些化合物和组合物的用途。
• Benzodiazepine CGRP receptor antagonists
  申请人：Merck & Co, Inc.

  公开号：US07196079B2

  公开（公告）日：2007-03-27

  The present invention is directed to compounds of Formula I: (where variables R1, R2, R3, R6, R7, G, J, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及一种化合物，其化学式为I：（其中变量R1、R2、R3、R6、R7、G、J、W、X和Y如本文所定义），该化合物可用作CGRP受体的拮抗剂，可用于治疗或预防CGRP参与的疾病，如头痛、偏头痛和丛集性头痛。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在预防或治疗CGRP参与的这些疾病中的应用。
• CGRP receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US07205292B2

  公开（公告）日：2007-04-17

  The present invention is directed to compounds of Formula I and Formula II: (where variables R1, R2, R3, R4, R6, A, B, G, J, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及公式I和公式II的化合物：（其中变量R1、R2、R3、R4、R6、A、B、G、J、W、X和Y的定义如本文所述），用作CGRP受体的拮抗剂，并用于治疗或预防CGRP参与的疾病，如头痛、偏头痛和集群头痛。本发明还涉及包含这些化合物的制药组合物，以及在预防或治疗CGRP参与的这些疾病中使用这些化合物和组合物的用途。
• [EN] FUSED RING-CONTAINING COMPOUND, APPLICATION THEREOF, AND COMPOSITION CONTAINING SAME<br/>[FR] COMPOSÉ CONTENANT UN CYCLE FUSIONNÉ, SON APPLICATION, ET COMPOSITION LE CONTENANT<br/>[ZH] 一种含稠环的化合物、其应用及含其的组合物
  申请人：GENEROS BIOPHARMA LTD

  公开号：WO2022083731A1

  公开（公告）日：2022-04-28

  一种含稠环的化合物、其应用及含其的组合物，具体为一种如式(II)所示的含稠环的化合物、其药学上可接受的盐、其溶剂合物或其药学上可接受的盐的溶剂合物，该类化合物具有较佳的STAT5抑制活性。