6-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one | 58859-52-2

• 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: 6-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one
• 英文别名: 6-chloro-1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one；6-chloro-1-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one；3-(piperidin-4-yl)-5-chloro-1H-benzimidazolone；4-(2,3-dihydro-6-chloro-2-oxo-benzoimidazol-1-yl)-piperidine；6-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one；6-chloro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one；5-chloro-3-piperidin-4-yl-1H-benzimidazol-2-one
• CAS: 58859-52-2
• 化学式: C₁₂H₁₄ClN₃O
• 分子量: 251.716
• InChiKey: FJCHFVDZYLYFBX-UHFFFAOYSA-N

物化性质

• 熔点：
  130 °C
• 密度：
  1.323±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one 在 titanium(IV) isopropylate 作用下， 以 乙醇 为溶剂， 反应 24.5h， 生成 6-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：

  吗丁啉杂质12 在 sodium hydroxide 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 6-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-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

• Method for treating allergies using substituted pyrazoles
  申请人：Butler R. Christopher

  公开号：US20050101587A9

  公开（公告）日：2005-05-12

  A method for treating an allergic condition, including an atopic allergic condition, using substituted pyrazoles.

  使用取代吡唑烷治疗过敏症状的方法，包括特应性过敏症状。
• Benzimidazolone and quinazolinone derivatives as agonists on human ORL1 receptors
  申请人：Den Hartog A.J. Jacobus

  公开号：US20050070528A1

  公开（公告）日：2005-03-31

  The invention relates to a group of novel benzimidazolone and quinazolinone derivatives which are agonists on human ORL1 (nociceptin) receptors. The invention also relates to the preparation of these compounds, to pharmaceutical compositions containing a pharmacologically active amount of at least one of these imidazolone and quinazolinone derivatives as an active ingredient, as well as to the use of these pharmaceutical compositions for the treatment of disorders in which ORL1 receptors are involved. The invention relates to compounds of the general formula (1): wherein the symbols have the meanings as given in the description.

  该发明涉及一组新型苯并咪唑酮和喹唑酮衍生物，这些衍生物是人类ORL1（nociceptin）受体的激动剂。该发明还涉及制备这些化合物，含有至少一种这些咪唑酮和喹唑酮衍生物的药理活性量作为活性成分的药物组合物，以及利用这些药物组合物治疗涉及ORL1受体的疾病。该发明涉及一般公式（1）的化合物：其中符号的含义如描述中所述。
• Novel inhibitors of chymase
  申请人：Hawkins J. Michael

  公开号：US20050176769A1

  公开（公告）日：2005-08-11

  The present invention is directed to a compound of formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof, and methods for treating inflammatory and serine protease mediated disorders.

  本发明涉及一种化合物，其化学式为(I)，以及制备这些化合物的方法、组合物、中间体和衍生物，以及治疗炎症和丝氨酸蛋白酶介导的疾病的方法。
• HETEROCYCLIC COMPOUND, APPLICATION THEREOF, AND COMPOSITION CONTAINING SAME
  申请人：Generos Biopharma Ltd.

  公开号：EP3960736A1

  公开（公告）日：2022-03-02

  A heterocyclic compound represented by formula XI, a pharmaceutically acceptable salt, a solvate, or a solvate of a pharmaceutically acceptable salt thereof, use thereof, and a composition containing the same. The compound is novel in structure and has good STAT5 inhibitory activity.

  由式XI表示的杂环化合物，其药用盐、溶剂合物，或其药用盐的溶剂合物，以及其用途和含有该化合物的组合物。该化合物在结构上是新颖的，并具有良好的STAT5抑制活性。
• 含杂芳基哌啶的青蒿素衍生物、其制备方法及 应用
  申请人：中国科学院上海药物研究所

  公开号：CN104211712B

  公开（公告）日：2017-04-05

  含杂芳基哌啶的青蒿素衍生物、其制备方法及应用。本发明涉及一种青蒿素衍生物，即通式I所示的化合物、其光学异构体、其药学上可接受的盐及其前药；其制备方法及用途。从本发明的公开内容可以看出，本发明所保护的青蒿素类衍生物具有优异的抗肿瘤活性，因此具有较好的应用前景。