6-fluoro-1-(piperidin-4-yl)-1-H-benzo[d]imidazol-2(3H)-on | 610323-35-8

• 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-fluoro-1-(piperidin-4-yl)-1-H-benzo[d]imidazol-2(3H)-on
• 英文别名: 6-fluoro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one；4-(2,3-dihydro-6-fluoro-2-oxo-benzoimidazol-1-yl)-piperidine；5-fluoro-3-piperidin-4-yl-1H-benzimidazol-2-one
• CAS: 610323-35-8
• 化学式: C₁₂H₁₄FN₃O
• 分子量: 235.261
• InChiKey: CNKJNOLPKVBSLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 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：
  3

反应信息

• 作为反应物：
  描述：

  6-fluoro-1-(piperidin-4-yl)-1-H-benzo[d]imidazol-2(3H)-on 、 2,3-dihydro-2,2-dimethyl-5-chloro-7-(oxiranyl-methoxy)-benzofuran 以 乙醇 为溶剂， 反应 72.0h， 以36.7%的产率得到1-((2,3-dihydro-2,2-dimethyl-5-chloro-benzofuran-7-yl)-oxy)-3-(4-(2,3-dihydro-2-oxo-6-fluoro-benzoimidazol-1-yl)-piperidin-1-yl)-propan-2-ol
  参考文献：
  名称：

  WO2008/146064

  摘要：

  公开号：
• 作为产物：
  描述：

  2,4-二氟硝基苯 在 platinum on activated charcoal sodium hydroxide 、 甲酸铵 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 6-fluoro-1-(piperidin-4-yl)-1-H-benzo[d]imidazol-2(3H)-on
  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

• Synthesis and SAR of analogs of the M1 allosteric agonist TBPB. Part II: Amides, sulfonamides and ureas—The effect of capping the distal basic piperidine nitrogen
  作者：Nicole R. Miller、R. Nathan Daniels、Thomas M. Bridges、Ashley E. Brady、P. Jeffrey Conn、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2008.09.032

  日期：2008.10

  developed through an iterative analog library approach, of analogs of the highly selective M1 allosteric agonist TBPB by deletion of the distal basic piperidine nitrogen by the formation of amides, sulfonamides and ureas. Despite the large change in basicity and topology, M1 selectivity was maintained.

  这封信描述了通过迭代类似物文库方法开发的高度选择性的M1变构激动剂TBPB类似物的进一步合成和SAR，该合成物是通过形成酰胺，磺酰胺和尿素来缺失远端碱性哌啶氮。尽管基本性和拓扑结构发生了很大变化，但仍保持了M1选择性。
• Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties
  作者：Thomas M. Bridges、Ashley E. Brady、J. Phillip Kennedy、R. Nathan Daniels、Nicole R. Miller、Kwango Kim、Micah L. Breininger、Patrick R. Gentry、John T. Brogan、Carrie K. Jones、P. Jeffrey Conn、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2008.09.023

  日期：2008.10

  This Letter describes the first account of the synthesis and SAR, developed through an iterative analogue library approach, of analogues of the highly selective M1 allosteric agonist TBPB. With slight structural changes, mAChR selectivity was maintained, but the degree of partial M1 agonism varied considerably.

  这封信描述了通过高度重复的M1变构激动剂TBPB的类似物通过迭代类似物库方法开发的合成和SAR的首次描述。在轻微的结构变化下，仍保持了mAChR选择性，但是部分M1激动的程度变化很大。
• [EN] NOVEL PIPERIDINYL-1,3-DIHYDRO-BENZOIMIDAZOL-2-ONES AS M1 AGONISTS<br/>[FR] NOUVELLES PIPÉRIDINYL-1,3-DIHYDROBENZOIMIDAZOL-2-ONES COMME AGONISTES DE M1
  申请人：LUNDBECK & CO AS H

  公开号：WO2009124882A1

  公开（公告）日：2009-10-15

  The present invention relates to novel M1 agonistic compounds of the present invention and their use in the treatment of cognitive impairment associated i.a. with schizophrenia and in the treatment of other diseases mediated by the muscarinic M1 receptor.

  本发明涉及本发明的新型M1激动剂化合物及其在治疗与精神分裂症相关的认知障碍以及在治疗由肌动蛋白M1受体介导的其他疾病中的应用。
• [EN] NOVEL 1,3-DIHYDRO-BENZOIMIDAZOL-2-ONES AS M1 AGONISTS<br/>[FR] NOUVEAUX 1,3-DIHYDRO-BENZOIMIDAZOL-2-ONES UTILISÉS EN TANT QU'AGONISTES M1
  申请人：LUNDBECK & CO AS H

  公开号：WO2009124883A1

  公开（公告）日：2009-10-15

  The present invention relates to novel MI agonistic compounds of the present invention. wherein R1 and R3 are idenpendently selected from H, cyano, halogen, such as F or C1, C1-6 alkoxy, such as methoxy, or C1-6 alkyI, such as methyl R2 is selected from H and halogen, such as F or C1; Y and Y' are individually selected from C1-3 alkyl, or Y and Y' together with the carbon atom to which they are attached, form a C3-7 cyctoalkyl group; and wherein each C1-3 alkyl and C3-7 cycloalkyl group may be optionally substituted with one or two substituents Z; Z is selected from hydrogen, C1-3 alkyl and halogen, such as F or C1; and their use in the treatment of cognitive impairment associated 1 a. w ith schizophrenia and in the treatment of other diseases mediated b> the muscarinic MI receptor

  本发明涉及本发明的新型MI激动剂化合物。其中，R1和R3分别选自H、氰基、卤素（如F或Cl）、C1-6烷氧基（如甲氧基）或C1-6烷基（如甲基）；R2选自H和卤素（如F或Cl）；Y和Y'分别选自C1-3烷基，或者Y和Y'与它们附着的碳原子一起形成C3-7环烷基；每个C1-3烷基和C3-7环烷基可以选择地用一个或两个取代基Z取代；Z选自氢、C1-3烷基和卤素（如F或Cl）；以及它们在治疗与精神分裂症相关的认知障碍以及治疗其他通过肌动蛋白MI受体介导的疾病中的应用。
• Remedy for sleep disturbance
  申请人：Teshima Koji

  公开号：US20050119308A1

  公开（公告）日：2005-06-02

  The present invention has been made based on the finding that a compound acting on the ORL-1 receptor as an agonist acts as a non-photic entrainment factor, and advances the circadian rhythm phase, and provides a novel therapeutic agent for a sleep disorder such as circadian rhythm sleep disorder, more particularly, an agent for the prophylaxis and/or treatment of a sleep disorder, which contains an ORL-1 receptor agonist, and a novel compound useful as such agent for the prophylaxis and/or treatment.

  本发明是基于发现得出的，即作用于ORL-1受体的化合物作为激动剂时，作为非光周期性调节因子，可以提前昼夜节律阶段，并提供一种新的治疗药物，用于治疗睡眠障碍，如昼夜节律睡眠障碍，更具体地说，是一种用于预防和/或治疗睡眠障碍的药物，其中包含ORL-1受体激动剂，并提供了一种作为该药物预防和/或治疗的有用化合物。