N-benzyl-4-[4-(4-fluorobenzyl)phenyl]-4-piperidinol | 202716-26-5

• 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: N-benzyl-4-[4-(4-fluorobenzyl)phenyl]-4-piperidinol
• 英文别名: N-Benzyl-4-[4-(4-E fluorophenyl)methylphenyl]-4-piperidinol；1-Benzyl-4-[4-[(4-fluorophenyl)methyl]phenyl]piperidin-4-ol
• CAS: 202716-26-5
• 化学式: C₂₅H₂₆FNO
• 分子量: 375.486
• InChiKey: UMRMIEMXLZEBGA-UHFFFAOYSA-N

物化性质

• 沸点：
  529.5±50.0 °C(Predicted)
• 密度：
  1.176±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-benzyl-4-[4-(4-fluorobenzyl)phenyl]-4-piperidinol 在 palladium dihydroxide 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、506.62 kPa 条件下， 以74%的产率得到4-[4-(4-fluorobenzyl)phenyl]-4-piperidinol
  参考文献：
  名称：

  Synthesis and biological evaluation of new 4-arylpiperidines and 4-aryl-4-piperidinols: dual Na+ and Ca2+ channel blockers with reduced affinity for dopamine D2 receptors

  摘要：

  A series of novel 4-arylpiperidines and 4-aryl-4-piperidinols (2a-f, 3a f and 4a-f) wits synthesized and evaluated for blocking effects on both neuronal Na+ and T-type Ca2+ channels and binding affinity for dopamine D-2 receptors. Most or the compounds blockaded both ion channels with potency greater than or equal to flunarizine Ia which was adopted as a reference standard. In addition, these compounds had significantly reduced affinity for dopamine D-2 receptors which is common in this class of structure. Compounds 2a-f, 3a-f and 4a-f exhibited potent anticonvulsant effects following systemic (ip) administration on audiogenic seizures in DBA/2 mice, indicating their excellent brain permeability. The neuroprotective activity of 2a, 3a and 4a was also assessed in a transient middle cerebral artery Occlusion (MCAO) model. These Compounds significantly reduced neuronal damage without affecting ischemic hyperthemia, while flunarizine Ia produced only minor reductions. In particular. 4a had 1.7-fold the potency in this MCAO model but only 1/20 the affinity for dopamine D-2 receptors of 1a. The Superposition of 2a, 3a and 4a on the basis of analyses of systematic conformation and similar structure has revealed that the cinnamyl, phenacyl and phenoxy-propanol groups are likely to be structurally and biologically equivalent. Moreover, the Superposition of 2a and 2f shows that diphenyl ether and biphenyl groups occupy a similar space, suggesting that both groups act as a bioisostere for the blockade of ion channels: however, this is not the case for dopamine D-2 receptors since only biphenyl Compounds such as 2f had high affinity similar to flunarizine Ia. Compound 4a (SUN N5030) has a good pharmacological profile and may be Useful in the alleviation and treatment or ischemic diseases. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00288-7
• 作为产物：
  描述：

  4-bromo-4'-fluorodiphenylmethanol 在 三乙基硅烷 、 正丁基锂 作用下， 以 乙醚 、 正己烷 、 三氟乙酸 为溶剂， 反应 3.0h， 生成 N-benzyl-4-[4-(4-fluorobenzyl)phenyl]-4-piperidinol
  参考文献：
  名称：

  Synthesis and biological evaluation of new 4-arylpiperidines and 4-aryl-4-piperidinols: dual Na+ and Ca2+ channel blockers with reduced affinity for dopamine D2 receptors

  摘要：

  A series of novel 4-arylpiperidines and 4-aryl-4-piperidinols (2a-f, 3a f and 4a-f) wits synthesized and evaluated for blocking effects on both neuronal Na+ and T-type Ca2+ channels and binding affinity for dopamine D-2 receptors. Most or the compounds blockaded both ion channels with potency greater than or equal to flunarizine Ia which was adopted as a reference standard. In addition, these compounds had significantly reduced affinity for dopamine D-2 receptors which is common in this class of structure. Compounds 2a-f, 3a-f and 4a-f exhibited potent anticonvulsant effects following systemic (ip) administration on audiogenic seizures in DBA/2 mice, indicating their excellent brain permeability. The neuroprotective activity of 2a, 3a and 4a was also assessed in a transient middle cerebral artery Occlusion (MCAO) model. These Compounds significantly reduced neuronal damage without affecting ischemic hyperthemia, while flunarizine Ia produced only minor reductions. In particular. 4a had 1.7-fold the potency in this MCAO model but only 1/20 the affinity for dopamine D-2 receptors of 1a. The Superposition of 2a, 3a and 4a on the basis of analyses of systematic conformation and similar structure has revealed that the cinnamyl, phenacyl and phenoxy-propanol groups are likely to be structurally and biologically equivalent. Moreover, the Superposition of 2a and 2f shows that diphenyl ether and biphenyl groups occupy a similar space, suggesting that both groups act as a bioisostere for the blockade of ion channels: however, this is not the case for dopamine D-2 receptors since only biphenyl Compounds such as 2f had high affinity similar to flunarizine Ia. Compound 4a (SUN N5030) has a good pharmacological profile and may be Useful in the alleviation and treatment or ischemic diseases. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00288-7

文献信息

• Arylpiperidinol and arylpiperidine derivatives and drugs containing the same
  申请人：Suntory Limited

  公开号：US06455549B1

  公开（公告）日：2002-09-24

  A pharmaceutical composition, especially a pharmaceutical composition for the alleviation or treatment of symptoms due to ischemic diseases and symptoms derived from seizures, epilepsy, and migraine, and a Ca2+ overload suppressant, containing an arylpiperidinol or arylpiperidine derivative having the formula (I): wherein, R is H, an optionally substituted phenyl, an optionally substituted phenoxy, or an optionally substituted benzoyl, A is a connecting bond, a cycloalkylene, or an alkenylene optionally substituted with a lower alkyl, B is an alkylene optionally substituted with OH or an alkoxy or —NHCO(CH2)n— where n is an integer of 1 to 5, E is a connecting bond, O, or a methylene, X is OH or H provided that when E is O or a methylene, X is not H, and Y and Z are independently H, a halogen, an alkoxy, or an alkyl optionally substituted with a halogen.

  一种制药组合物，特别是用于缓解或治疗缺血性疾病和因癫痫、癫痫和偏头痛引起的症状的制药组合物，以及Ca2+过载抑制剂，含有具有以下式（I）的芳基哌啶醇或芳基哌啶衍生物：其中，R是H，可选择地取代的苯基，可选择地取代的苯氧基，或可选择地取代的苯甲酰基，A是连接键，环烷烃基，或可选择地取代的烯烃基，B是可选择地取代的烷基，其中取代基为OH或烷氧基，或-NHCO(CH2)n—，其中n为1至5的整数，E是连接键，O，或亚甲基，X是OH或H，条件是当E为O或亚甲基时，X不是H，Y和Z分别是H，卤素，烷氧基，或可选择地取代的烷基，其取代基为卤素。
• ARYLPIPERIDINOL AND ARYLPIPERIDINE DERIVATIVES AND DRUGS CONTAINING THE SAME
  申请人：SUNTORY LIMITED

  公开号：EP0867183A1

  公开（公告）日：1998-09-30

  A pharmaceutical composition, especially a pharmaceutical composition for the alleviation or treatment of symptoms due to ischemic diseases and symptoms derived from seizures, epilepsy, and migraine, and a Ca2+ overload suppressant, containing an arylpiperidinol or arylpiperidine derivative having the formula (I): wherein, R is H, an optionally substituted phenyl, an optionally substituted phenoxy, or an optionally substituted benzoyl, A is a connecting bond, a cycloalkylene, or an alkenylene optionally substituted with a lower alkyl, B is an alkylene optionally substituted with OH or an alkoxy or -NHCO(CH2)n- where n is an integer of 1 to 5, E is a connecting bond, O, or a methylene, X is OH or H provided that when E is O or a methylene, X is not H, and Y and Z are independently H, a halogen, an alyoxy, or an alyyl optionally substituted with a halogen.

  一种药物组合物，特别是一种用于缓解或治疗缺血性疾病引起的症状和癫痫发作、癫痫和偏头痛引起的症状的药物组合物，以及一种Ca2+超载抑制剂，含有具有式(I)的芳基哌啶醇或芳基哌啶衍生物： 其中，R 是 H、任选取代的苯基、任选取代的苯氧基或任选取代的苯甲酰基，A 是连接键、环烷基或任选被低级烷基取代的烯基、B 是任选被 OH 或烷氧基或-NHCO(CH2)n-取代的亚烷基，其中 n 是 1 至 5 的整数；E 是连接键、O 或亚甲基；X 是 OH 或 H，但当 E 是 O 或亚甲基时，X 不是 H；Y 和 Z 独立地是 H、卤素、烯丙基氧基或任选被卤素取代的烯丙基。
• Arylpiperidinol and arylpiperidine derivatives and pharmaceuticals containing the same
  申请人：——

  公开号：US20030130312A1

  公开（公告）日：2003-07-10

  A pharmaceutical composition, especially a pharmaceutical composition for the alleviation or treatment of symptoms due to ischemic diseases and symptoms derived from seizures, epilepsy, and migraine, and a Ca 2+ overload suppressant, containing an arylpiperidinol or arylpiperidine derivative having the formula (I): 1 wherein, R is H, an optionally substituted phenyl, an optionally substituted phenoxy, or an optionally substituted benzoyl, A is a connecting bond, a cycloalkylene, or an alkenylene optionally substituted with a lower alkyl, B is an alkylene optionally substituted with OH or an alkoxy or —NHCO(CH 2 ) n — where n is an integer of 1 to 5, E is a connecting bond, O, or a methylene, X is OH or H provided that when E is O or a methylene, X is not H, and Y and Z are independently H, a halogen, an alkoxy, or an alkyl optionally substituted with a halogen.

  一种药物组合物，特别是一种用于缓解或治疗缺血性疾病引起的症状以及癫痫发作、癫痫和偏头痛引起的症状的药物组合物，以及一种 Ca 2&plus； 过载抑制剂，含有具有式（I）的芳基哌啶醇或芳基哌啶衍生物： 1 其中，R 是 H、任选取代的苯基、任选取代的苯氧基或任选取代的苯甲酰基；A 是连接键、环烷基或任选被低级烷基取代的烯基；B 是任选被 OH 或烷氧取代的烷基或 -NHCO(CH 2 ) n - 其中 n 是 1 至 5 的整数，E 是连接键、O 或亚甲基，X 是 OH 或 H，但当 E 是 O 或亚甲基时，X 不是 H，Y 和 Z 独立地是 H、卤素、烷氧基或任选被卤素取代的烷基。
• US6455549B1
  申请人：——

  公开号：US6455549B1

  公开（公告）日：2002-09-24
• US6706734B2
  申请人：——

  公开号：US6706734B2

  公开（公告）日：2004-03-16