3-fluoro-5-(piperazin-1-yl)benznitrile | 752967-51-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-fluoro-5-(piperazin-1-yl)benznitrile
• 英文别名: 3-Fluoro-5-(piperazin-1-yl)benzonitrile；3-fluoro-5-piperazin-1-ylbenzonitrile
• CAS: 752967-51-4
• 化学式: C₁₁H₁₂FN₃
• 分子量: 205.235
• InChiKey: ZWIIXAJWAAWFHJ-UHFFFAOYSA-N

物化性质

• 沸点：
  372.3±42.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  39.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-fluoro-5-(piperazin-1-yl)benznitrile 在 盐酸 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 50.0h， 生成
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Novel Pyrimidinyl Pyrazole Derivatives. III. Synthesis and Antitumor Activity of 3-Phenylpiperazinyl-1-trans-propenes

  摘要：

  一系列新型的3-[4-苯基-1-哌嗪基]-1-[5-甲基-1-(2-嘧啶基)-4-吡唑基]-1-反式丙烯及其相关化合物被合成，并通过其对几种肿瘤细胞系的体外细胞毒性活性和对某些肿瘤模型的体内抗肿瘤活性进行了评估，这些化合物既可以通过腹腔注射给药，也可以口服给药。具有3-氯吡啶-2-基团（9g）和3-氟-5-取代苯基哌嗪基团（29b、c和e）的化合物在体外测试中显示出显著的细胞毒性。其中，3-氰基-5-氟苯基衍生物（29b）表现出对包括人癌在内的几种肿瘤细胞的强效抗肿瘤活性，且在老鼠中没有引起不良反应。

  DOI：

  10.1248/cpb.53.153
• 作为产物：
  描述：

  3-氟-5-硝基苯腈 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 乙醇 、 正丁醇 为溶剂， 反应 28.0h， 生成 3-fluoro-5-(piperazin-1-yl)benznitrile
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Novel Pyrimidinyl Pyrazole Derivatives. III. Synthesis and Antitumor Activity of 3-Phenylpiperazinyl-1-trans-propenes

  摘要：

  一系列新型的3-[4-苯基-1-哌嗪基]-1-[5-甲基-1-(2-嘧啶基)-4-吡唑基]-1-反式丙烯及其相关化合物被合成，并通过其对几种肿瘤细胞系的体外细胞毒性活性和对某些肿瘤模型的体内抗肿瘤活性进行了评估，这些化合物既可以通过腹腔注射给药，也可以口服给药。具有3-氯吡啶-2-基团（9g）和3-氟-5-取代苯基哌嗪基团（29b、c和e）的化合物在体外测试中显示出显著的细胞毒性。其中，3-氰基-5-氟苯基衍生物（29b）表现出对包括人癌在内的几种肿瘤细胞的强效抗肿瘤活性，且在老鼠中没有引起不良反应。

  DOI：

  10.1248/cpb.53.153

文献信息

• [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<br/>[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
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2017079641A1

  公开（公告）日：2017-05-11

  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, Li, L 2, Ri, R 2, R 3, R 4, R 5, 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-(l-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。
• 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。
• 5-[(PIPERAZIN-1-YL)-3-OXO-PROPYL]-IMIDAZOLIDINE-2,4-DIONE DERIVATIVES AS ADAMTS INHIBITORS FOR THE TREATMENT OF OSTEOARTHRITIS
  申请人：Galapagos NV

  公开号：EP3237406B1

  公开（公告）日：2019-02-06
• 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
• 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.