ethyl 1-benzyl-4-(cyanomethyl)piperidine-4-carboxylate | 867006-18-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: ethyl 1-benzyl-4-(cyanomethyl)piperidine-4-carboxylate
• CAS: 867006-18-6
• 化学式: C₁₇H₂₂N₂O₂
• 分子量: 286.374
• InChiKey: KWUPGDLEHKHZMS-UHFFFAOYSA-N

物化性质

• 沸点：
  411.9±35.0 °C(Predicted)
• 密度：
  1.104±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  53.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 1-benzyl-4-(cyanomethyl)piperidine-4-carboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以100%的产率得到[4-(2-aminoethyl)-1-benzylpiperidin-4-yl]methanol
  参考文献：
  名称：

  [EN] N-[2-(1 -BENZYLPIPERIDIN-4-YL)ETHYL]-4-(PYRAZIN-2-YL)-PIPERAZINE-1 -CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS MUSCARINIC RECEPTOR 4 (M4) ANTAGONISTS FOR TREATING NEUROLOGICAL DISEASES
  [FR] DÉRIVÉS DE N-[2-(1-BENZYLPIPÉRIDIN-4-YL)ÉTHYL]-4-(PYRAZIN-2-YL)-PIPÉRAZINE-1-CARBOXAMIDE ET COMPOSÉS APPARENTÉS EN TANT QU'ANTAGONISTES DU RÉCEPTEUR MUSCARINIQUE 4 (M4) POUR LE TRAITEMENT DE MALADIES NEUROLOGIQUES

  摘要：

  本文提供了以下化学式（I）的小分子化合物，或其立体异构体、互变异构体、溶剂化合物、酯或药用可接受的盐，其中A、B、C、Li、L 2、Ri、R 2、R 3、R 4、R 5、w、x、y和z的定义如本文所述。还公开了通过拮抗毒蕈碱受体来治疗疾病/障碍的方法，包括特别是拮抗毒蕈碱受体4（M4）。这些疾病/障碍包括神经系统疾病/障碍，如阿尔茨海默病、路易体痴呆症以及与精神分裂症、帕金森病、药物引起的帕金森综合症、运动障碍、肌张力障碍、舞蹈症、左多巴诱发的运动障碍、脑瘫、进行性核上性麻痹和亨廷顿病相关的认知缺陷等。首选化合物是例如N-[2-(1-苄基哌啶-4-基)乙基]-4-(吡嗪-2-基)-哌嗪-1-甲酰胺衍生物和相关化合物，其中吡嗪已被取代为例如吡啶、嘧啶、吡啶或苯基。

  公开号：

  WO2017079641A1
• 作为产物：
  描述：

  1-苄基-4-哌啶甲酸乙酯 、 溴乙腈 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以56%的产率得到ethyl 1-benzyl-4-(cyanomethyl)piperidine-4-carboxylate
  参考文献：
  名称：

  [EN] N-[2-(1 -BENZYLPIPERIDIN-4-YL)ETHYL]-4-(PYRAZIN-2-YL)-PIPERAZINE-1 -CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS MUSCARINIC RECEPTOR 4 (M4) ANTAGONISTS FOR TREATING NEUROLOGICAL DISEASES
  [FR] DÉRIVÉS DE N-[2-(1-BENZYLPIPÉRIDIN-4-YL)ÉTHYL]-4-(PYRAZIN-2-YL)-PIPÉRAZINE-1-CARBOXAMIDE ET COMPOSÉS APPARENTÉS EN TANT QU'ANTAGONISTES DU RÉCEPTEUR MUSCARINIQUE 4 (M4) POUR LE TRAITEMENT DE MALADIES NEUROLOGIQUES

  摘要：

  本文提供了以下化学式（I）的小分子化合物，或其立体异构体、互变异构体、溶剂化合物、酯或药用可接受的盐，其中A、B、C、Li、L 2、Ri、R 2、R 3、R 4、R 5、w、x、y和z的定义如本文所述。还公开了通过拮抗毒蕈碱受体来治疗疾病/障碍的方法，包括特别是拮抗毒蕈碱受体4（M4）。这些疾病/障碍包括神经系统疾病/障碍，如阿尔茨海默病、路易体痴呆症以及与精神分裂症、帕金森病、药物引起的帕金森综合症、运动障碍、肌张力障碍、舞蹈症、左多巴诱发的运动障碍、脑瘫、进行性核上性麻痹和亨廷顿病相关的认知缺陷等。首选化合物是例如N-[2-(1-苄基哌啶-4-基)乙基]-4-(吡嗪-2-基)-哌嗪-1-甲酰胺衍生物和相关化合物，其中吡嗪已被取代为例如吡啶、嘧啶、吡啶或苯基。

  公开号：

  WO2017079641A1

文献信息

• Compounds of formulas (VII), (VIII), (IX), (XI), (XII), (XIII), and (XIV) as muscarinic receptor 4(M4) antagonists for treating neurological diseases
  申请人：Neurocrine Biosciences, Inc.

  公开号：US11033539B2

  公开（公告）日：2021-06-15

  Provided herein are small molecule compounds of the following formula (I): or a stereoisomer, tautomer, solvate, ester or pharmaceutically acceptable salt thereof, wherein A, B, C, L1, L2, R2, R3, R4, R3, w, x, y and z are as defined herein. Methods for treating diseases/disorders by antagonizing muscarinic receptors, including specifically antagonizing muscarinic receptor 4 (M4), are also disclosed. Such diseases/disorders are e.g. neurological diseases/disorders such as e.g. Alzheimer's Disease, Lewy Body Dementia and the cognitive deficits associated with schizophrenia, Parkinson's Disease, drug induced Parkinsonism, dyskinesias, dystonia, chorea, levodopa induced dyskinesia, cerebral palsy, progressive supranuclear palsy, and Huntington's disease. Preferred compounds are e.g. N-[2-(1-benzylpiperidin-4-yl)ethyl]-4-(pyrazin-2-yl)-piperazine-1-carboxamide derivatives and related compounds wherein the pyrazine has been replaced by e.g. pyridazine, pyrimidine, pyridine or phenyl.

  本文提供了下式（I）的小分子化合物：或其立体异构体、同分异构体、溶液剂、酯或药学上可接受的盐，其中 A、B、C、L1、L2、R2、R3、R4、R3、w、x、y 和 z 如本文所定义。还公开了通过拮抗毒蕈碱受体（包括特异性拮抗毒蕈碱受体 4 (M4)）来治疗疾病/紊乱的方法。此类疾病/障碍包括神经系统疾病/障碍，例如阿尔茨海默病、路易体痴呆和与精神分裂症相关的认知障碍、帕金森病、药物诱发的帕金森症、运动障碍、肌张力障碍、舞蹈症、左旋多巴诱发的运动障碍、脑性麻痹、进行性核上性麻痹和亨廷顿氏病。首选化合物为 N-[2-(1-苄基哌啶-4-基)乙基]-4-(吡嗪-2-基)-哌嗪-1-甲酰胺衍生物及相关化合物，其中吡嗪已被哒嗪、嘧啶、吡啶或苯基等取代。
• SUBSTITUTED DIAZA-SPIRO-[5.5 -UNDECANE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS
  申请人：Janssen Pharmaceutica NV

  公开号：EP1735312B1

  公开（公告）日：2008-12-10
• N-[2-(1 -BENZYLPIPERIDIN-4-YL)ETHYL]-4-(PYRAZIN-2-YL)-PIPERAZINE-1 -CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS MUSCARINIC RECEPTOR 4 (M4) ANTAGONISTS FOR TREATING NEUROLOGICAL DISEASES
  申请人：NEUROCRINE BIOSCIENCES, INC.

  公开号：EP3371164A1

  公开（公告）日：2018-09-12
• Substituted Diaza-Spiro-[5.5]-Undecane Derivaties and Their Use as Neurokinin Antagonists
  申请人：Janssens Eduard Frans

  公开号：US20070232636A1

  公开（公告）日：2007-10-04

  This invention concerns substituted diaza-spiro-[5.5]-undecane derivatives having neurokinin antagonistic activity, in particular NK 1 antagonistic activity, a combined NK 1 /NK 2 antagonistic activity, a combined NK 1 /NK 3 antagonistic activity and a combined NK 1 /NK 2 /NK 3 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the treatment and/or prophylaxis of schizophrenia, emesis, anxiety and depression, irritable bowel syndrome (IBS), circadian rhythm disturbances, pre-eclampsia, nociception, pain, in particular visceral and neuropathic pain, pancreatitis, neurogenic inflammation, asthma, COPD and micturition disorders such as urinary incontinence. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.
• N-[2-(1-BENZYLPIPERIDIN-4-YL)ETHYL]-4-(PYRAZIN-2-YL)-PIPERAZINE-1-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS MUSCARINIC RECEPTOR 4 (M4) ANTAGONISTS FOR TREATING NEUROLOGICAL DISEASES
  申请人：Neurocrine Biosciences, Inc.

  公开号：US20180325887A1

  公开（公告）日：2018-11-15

  Provided herein are small molecule compounds of the following formula (I): or a stereoisomer, tautomer, solvate, ester or pharmaceutically acceptable salt thereof, wherein A, B, C, L 1 , L 2 , R 2 , R 3 , R 4 , R 3 , w, x, y and z are as defined herein. Methods for treating diseases/ disorders by antagonizing muscarinic receptors, including specifically antagonizing muscarinic receptor 4 (M4), are also disclosed. Such diseases/disorders are e.g. neurological diseases/disorders such as e.g. Alzheimer's Disease, Lewy Body Dementia and the cognitive deficits associated with schizophrenia, Parkinson's Disease, drug induced Parkinsonism, dyskinesias, dystonia, chorea, levodopa induced dyskinesia, cerebral palsy, progressive supranuclear palsy, and Huntington's disease. Preferred compounds are e.g. N-[2-(1-benzylpiperidin-4-yl)ethyl]-4-(pyrazin-2-yl)-piperazine- 1 -carboxamide derivatives and related compounds wherein the pyrazine has been replaced by e.g. pyridazine, pyrimidine, pyridine or phenyl.