5-Ethyl-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one | 107618-04-2

• 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: 5-Ethyl-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one
• 英文别名: 6-ethyl-3-piperidin-4-yl-1H-benzimidazol-2-one
• CAS: 107618-04-2
• 化学式: C₁₄H₁₉N₃O
• 分子量: 245.324
• InChiKey: ZKMUEGOYVRLLLL-UHFFFAOYSA-N

物化性质

• 熔点：
  200 °C
• 密度：
  1.162±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 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：
  44.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-羟甲基-1,4-苯并二噁烷对甲苯磺酸酯 、 5-Ethyl-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one 在 三乙胺 、 potassium iodide 作用下， 以 二甲基亚砜 为溶剂， 反应 20.0h， 以23%的产率得到3-[1-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)piperidin-4-yl]-6-ethyl-1H-benzimidazol-2-one
  参考文献：
  名称：

  Synthesis and neuroleptic activity of a series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimidazolone derivatives

  摘要：

  A series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimid azolones with various substituents in both aromatic rings have been synthesized and tested for neuroleptic activity (antiapomorphine effects and [3H]spiroperidol binding) as well as extrapyramidal effects (cataleptogenic effect). A strong dependence of activity on the 5-substituent in the benzimidazolone moiety could be demonstrated. Some compounds show a large split between the desired antiapomorphine and the undesired extrapyramidal effect. From these, 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]-5-chlor obenzimidazol-2-one hydrochloride (HR 723), 12, has been selected for further preclinical and toxicological profiling.

  DOI：

  10.1021/jm00388a012
• 作为产物：
  描述：

  ethyl 4-(2-amino-4-ethylanilino)piperidine-1-carboxylate 在 sodium hydroxide 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.5h， 生成 5-Ethyl-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one
  参考文献：
  名称：

  Synthesis and neuroleptic activity of a series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimidazolone derivatives

  摘要：

  A series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimid azolones with various substituents in both aromatic rings have been synthesized and tested for neuroleptic activity (antiapomorphine effects and [3H]spiroperidol binding) as well as extrapyramidal effects (cataleptogenic effect). A strong dependence of activity on the 5-substituent in the benzimidazolone moiety could be demonstrated. Some compounds show a large split between the desired antiapomorphine and the undesired extrapyramidal effect. From these, 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]-5-chlor obenzimidazol-2-one hydrochloride (HR 723), 12, has been selected for further preclinical and toxicological profiling.

  DOI：

  10.1021/jm00388a012

文献信息

• Benzimidazolone derivatives
  申请人：——

  公开号：US20040147506A1

  公开（公告）日：2004-07-29

  This invention relates to benzimidazolone derivatives, represented by compounds of a general formula [I] 1 [in which R 1 and R 2 stand for, e.g., hydrogen atoms; R 3a , R 3b , R 4 , R 5 stand for, e.g., hydrogen atoms and alkyl groups; R 6 stands for e.g., aryl or heteroaryl groups; A ring stands for 5- to 8-membered aliphatic heterocyclic ring containing one nitrogen atom; and Z stands for carbonyl group or sulfonyl group]. The benzimidazolone derivatives of the invention exhibit antagonism to muscarinic acetylcholine receptors, and are useful as treating agent and/or prophylactic of Parkinson's disease, drug-induced parkinsonism, dystonia, akinesia, pancreatitis, bilestone/cholecystitis, biliary dyskinesia, achalasia, pain, itch, cholinergic urticaria, irritable bowel syndrome, vomiting, nausea, dizziness, Meniere's disease, motion sickness and urinary disturbance.

  本发明涉及苯并咪唑酮衍生物，其由一般式[I]中的化合物表示，其中R1和R2代表氢原子；R3a、R3b、R4、R5代表氢原子和烷基基团；R6代表芳基或杂环芳基基团；A环代表含有一个氮原子的5-至8-成员脂肪族杂环环；Z代表羰基团或磺酰基团。本发明的苯并咪唑酮衍生物表现出对肌动蛋白乙酰胆碱受体的拮抗作用，可用作帕金森病、药物诱导的帕金森综合征、肌张力障碍、运动障碍、胰腺炎、胆石/胆囊炎、胆道运动障碍、食管失弛缓症、疼痛、瘙痒、胆碱能荨麻疹、肠易激综合征、呕吐、恶心、眩晕、梅尼埃病、晕动病和尿液障碍的治疗剂和/或预防剂。
• BENZIMIDAZOLONE DERIVATIVES
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1386920A1

  公开（公告）日：2004-02-04

  This invention relates to benzimidazolone derivatives, represented by compounds of a general formula [I]    [in which R1 and R2 stand for, e.g., hydrogen atoms; R3a, R3b, R4, R5 stand for, e.g., hydrogen atoms and alkyl groups; R6 stands for e.g., aryl or heteroaryl groups; A ring stands for 5- to 8-membered aliphatic heterocyclic ring containing one nitrogen atom; and Z stands for carbonyl group or sulfonyl group]. The benzimidazolone derivatives of the invention exhibit antagonism to muscarinic acetylcholine receptors, and are useful as treating agent and/or prophylactic of Parkinson's disease; drug-induced parkinsonism, dystonia, akinesia, pancreatitis, bilestone/cholecystitis, biliary dyskinesia, achalasia, pain, itch, cholinergic urticaria, irritable bowel syndrome, vomiting, nausea, dizziness, Meniere's disease, motion sickness and urinary disturbance.

  本发明涉及苯并咪唑酮衍生物，以通式[I]的化合物为代表。 [其中 R1 和 R2 代表氢原子；R3a、R3b、R4、R5 代表氢原子和烷基；R6 代表芳基或杂芳基；A 环代表含有一个氮原子的 5 至 8 元脂肪杂环；Z 代表羰基或磺酰基]。 本发明的苯并咪唑酮衍生物对毒蕈碱乙酰胆碱受体具有拮抗作用，可作为帕金森病的治疗药物和/或预防药物；药物诱发的帕金森病、肌张力障碍、运动障碍、胰腺炎、胆石症/胆囊炎、胆汁运动障碍、贲门失弛缓症、疼痛、瘙痒、胆碱能性荨麻疹、肠易激综合征、呕吐、恶心、头晕、美尼尔氏病、晕车和排尿障碍。
• HENNING R.; LATTRELL R.; GARHARDS H. J.; LEVEN M., J. MED. CHEM., 30,(1987) N 5, 814-819
  作者：HENNING R.、 LATTRELL R.、 GARHARDS H. J.、 LEVEN M.

  DOI：——

  日期：——
• US7164024B2
  申请人：——

  公开号：US7164024B2

  公开（公告）日：2007-01-16
• Synthesis and neuroleptic activity of a series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimidazolone derivatives
  作者：Rainer Henning、Rudolf Lattrell、Hermann J. Gerhards、Margret Leven

  DOI：10.1021/jm00388a012

  日期：1987.5

  A series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimid azolones with various substituents in both aromatic rings have been synthesized and tested for neuroleptic activity (antiapomorphine effects and [3H]spiroperidol binding) as well as extrapyramidal effects (cataleptogenic effect). A strong dependence of activity on the 5-substituent in the benzimidazolone moiety could be demonstrated. Some compounds show a large split between the desired antiapomorphine and the undesired extrapyramidal effect. From these, 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]-5-chlor obenzimidazol-2-one hydrochloride (HR 723), 12, has been selected for further preclinical and toxicological profiling.