1-ethyl-3-piperidine-4-yl-1,3-dihydrobenzoimidazol-2-one | 53786-29-1

• 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: 1-ethyl-3-piperidine-4-yl-1,3-dihydrobenzoimidazol-2-one
• 英文别名: 1-(piperidin-4-yl)-3-ethyl-1,3-dihydro-2-one；1-ethyl-3-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one；1,3-dihydro-1-ethyl-3-(4-piperidinyl)-2H-benzimidazol-2-one；4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidine；1-Ethyl-3-piperidin-4-ylbenzimidazol-2-one
• CAS: 53786-29-1
• 化学式: C₁₄H₁₉N₃O
• 分子量: 245.324
• InChiKey: DUHJTBXBKZJJGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-异丙基环己酮 、 1-ethyl-3-piperidine-4-yl-1,3-dihydrobenzoimidazol-2-one 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 以62%的产率得到1-ethyl-3-{1-[4-(1-methylethyl)cyclohexyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one
  参考文献：
  名称：

  Quantitative Signaling and Structure-Activity Analyses Demonstrate Functional Selectivity at the Nociceptin/Orphanin FQ Opioid Receptor

  摘要：

  对 G 蛋白偶联受体（GPCR）系统进行综合研究，将选择性配体、G 蛋白与停滞素-2/3 偶联的定量比较以及结构-活性关系模型结合起来，但这种研究较少采用。在这里，我们研究了阿片受体家族中最新发现的成员--神经痛素/表素 FQ 阿片受体（NOPR）的偏向信号传导。我们利用实时活细胞测定法确定了几种 NOPR 选择性配体在上游 GPCR 信号转导（G 蛋白和 arrestin 通路）中的信号转导特征，以确定它们的相对转导系数和信号转导偏差。作为这一分析的补充，我们在 NOPR 拮抗剂 J-113,397 [(±)-1-[(3 R *,4 R *)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2 H -benzimidazol-2-one] 的基础上设计了新型配体，以探索结构-活性关系。我们的研究表明，NOPR 具有偏向信号传导的能力。此外，NOPR 选择性配体 MCOPPB [1-[1-(1- 甲基环辛基)-4-哌啶基]-2-(3 R )-3- 哌啶基-1 H -苯并咪唑三盐酸盐] 和 NNC 63-0532 [8-(1-naphthalenylmethyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]癸烷-3-乙酸甲酯]是偏向 G 蛋白的激动剂。此外，J-113,397 的微小结构修饰可使信号从拮抗剂活性显著转变为部分激动剂活性。我们通过结合位置的硅学建模来探索这些发现。这项研究首次证明了神经肽阿片受体的功能选择性和偏向配体的鉴定。

  DOI：

  10.1124/mol.115.099150
• 作为产物：
  描述：

  4-[(2-硝基苯基)氨基]哌啶-1-羧酸乙酯 在 platinum on activated charcoal sodium hydroxide 、 甲酸铵 、 双(三甲基硅烷基)氨基钾 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 1-ethyl-3-piperidine-4-yl-1,3-dihydrobenzoimidazol-2-one
  参考文献：
  名称：

  Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors

  摘要：

  A novel series of competitive, reversible cathepsin S (Cats) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of Cats inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of cathepsin S. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.045

文献信息

• .alpha..sub.1a adrenergic receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US06096763A1

  公开（公告）日：2000-08-01

  This invention relates to novel compounds, their synthesis and use as selective .alpha..sub.1a adrenergic receptor antagonists. One application of the compounds is in the treatment of benign prostatic hyperplasia. The compounds are selective in their ability to relax smooth muscle tissue enriched in the .alpha..sub.1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.

  该发明涉及新型化合物，它们的合成以及作为选择性α1a肾上腺素受体拮抗剂的用途。这些化合物的一个应用是用于治疗良性前列腺增生。这些化合物在其能够放松富含α1a受体亚型的平滑肌组织方面具有选择性，同时不会引起低血压。这样的组织之一是围绕尿道内膜的组织。因此，这些化合物的一个用途是为患有良性前列腺增生的男性提供急性缓解，通过促进尿液流动。这些化合物的另一个用途是与人类5α-还原酶抑制剂化合物结合，从而实现对良性前列腺增生影响的急性和慢性缓解。
• Alpha 1a adrenergic receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US05952351A1

  公开（公告）日：1999-09-14

  This invention relates to novel compounds, their synthesis and use as selective .alpha..sub.1a adrenergic receptor antagonists. One application of the compounds is in the treatment of benign prostatic hyperplasia. The compounds are selective in their ability to relax smooth muscle tissue enriched in the .alpha..sub.1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.

  这项发明涉及新型化合物，它们的合成以及用作选择性α1a肾上腺素受体拮抗剂的用途。这些化合物的一个应用是治疗良性前列腺增生。这些化合物在其放松富含α1a受体亚型的平滑肌组织的能力上具有选择性，同时不会引起低血压。这样的组织之一位于尿道内膜周围。因此，这些化合物的一个用途是为患有良性前列腺增生的男性提供急性缓解，从而减轻尿流受阻。这些化合物的另一个用途是与人类5α-还原酶抑制剂化合物结合，以实现对良性前列腺增生影响的急性和慢性缓解。
• Structure–activity studies on the nociceptin/orphanin FQ receptor antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4′-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide
  作者：Claudio Trapella、Carmela Fischetti、Michela Pela’、Ilaria Lazzari、Remo Guerrini、Girolamo Calo’、Anna Rizzi、Valeria Camarda、David G. Lambert、John McDonald、Domenico Regoli、Severo Salvadori

  DOI：10.1016/j.bmc.2009.05.068

  日期：2009.7

  Twelve derivatives of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) antagonist 1-benzyl-N-3-[spiroisobenzofuran-1(3H),4'-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide (Comp 24) were synthesised and tested in binding experiments performed on CHOhNOP cell membranes. Among them, a novel interesting NOP receptor antagonist (compound 35) was identified by blending chemical moieties taken from different NOP receptor ligands. In vitro in various assays, Compound 35 consistently behaved as a pure, highly potent (pA(2) in the range 8.0-9.9), competitive and NOP selective antagonist. However compound 35 was found inactive when challenged against N/OFQ in vivo in the mouse tail withdrawal assay. Thus the usefulness of the novel NOP ligand compound 35 is limited to in vitro investigations. (C) 2009 Elsevier Ltd. All rights reserved.
• ALPHA 1a ADRENERGIC RECEPTOR ANTAGONISTS
  申请人：MERCK & CO., INC.

  公开号：EP0812196A1

  公开（公告）日：1997-12-17
• EP0812196A4
  申请人：——

  公开号：EP0812196A4

  公开（公告）日：1998-05-20