N-benzyl-4-(3-fluoro-4-phenyl)phenyl-4-piperidinol | 202604-68-0

• 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-(3-fluoro-4-phenyl)phenyl-4-piperidinol
• 英文别名: 1-Benzyl-4-(3-fluoro-4-phenylphenyl)piperidin-4-ol
• CAS: 202604-68-0
• 化学式: C₂₄H₂₄FNO
• 分子量: 361.459
• InChiKey: XBMAUERHVMFYKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 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-(3-fluoro-4-phenyl)phenyl-4-piperidinol 在 palladium dihydroxide 氢气 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 20.0 ℃ 、506.62 kPa 条件下， 生成 (E)-4-(3-Fluoro-4-phenyl)phenyl-1-(3-phenyl-2-propenyl)-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：

  N-苄基哌啶酮 、 4-溴-2-氟联苯 生成 N-benzyl-4-(3-fluoro-4-phenyl)phenyl-4-piperidinol
  参考文献：
  名称：

  Arylpiperidinopropanol and arylpiperazinopropanol derivatives and pharmaceuticals containing the same

  摘要：

  一种具有化学式（I）或其盐、水合物、水合盐或溶剂络合物的化合物：其中R1至R4独立地代表H、卤素、OH、烷氧基、可选择地取代的烷基、芳基或芳基烷基，R5代表H、可选择地取代的烷基、芳基或芳基烷基，E1代表O、S或—NR6，其中R6代表H、可选择地取代的烷基、芳基或芳基烷基，E2代表O、S或—NR7，其中R7代表H、可选择地取代的烷基、芳基或芳基烷基，A代表CH、C(OH)或N，X代表H、卤素、烷氧基或可选择地取代的烷基，Q代表可选择地取代的苯基、苯氧基、苄基苯基或环烷氧基，其中当E1代表O或S时，E2不代表O或S，具有抑制细胞毒性Ca2+超载和脂质过氧化作用，并对缓解和治疗因缺血性疾病等症状而进行的药物制剂具有有效作用。

  公开号：

  US06407099B1

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。
• Arylipiperdinopropanol and arylipiperazinopropanol derivatives and pharmaceuticals containing the same
  申请人：Annoura Hirokazu

  公开号：US20050101610A1

  公开（公告）日：2005-05-12

  A compound having the formula (I) or its salt, hydrate, hydrate salt or solvate: wherein R 1 to R 4 independently represent H, halogen, OH, alkoxy, optionally substituted alkyl, aryl, or aralkyl group, R 5 represents H, optionally substituted alkyl, aryl, or aralkyl group, E 1 represents O, S, or —NR 6 , where R 6 represents H, an optionally substituted alkyl, aryl, or aralkyl group, E 2 represents O, S, or —NR 7 , where R 7 represents H, an optionally substituted alkyl, aryl, or aralkyl group, A represents CH, C(OH), or N, X represents H, halogen, alkoxy, or an optionally substituted alkyl group, and Q represents an optionally substituted phenyl group, phenoxy, phenylmethyl, or cycloalkyloxy group, where when E 1 represents O or S, E 2 does not represent O or S, which has an action of suppressing the cytotoxic Ca 2+ overload and lipid peroxidation and effective for pharmaceutical preparation for the alleviation and treatment of symptoms due to ischemic diseases, etc.

  化合物具有以下公式(I)或其盐，水合物，水合盐或溶剂化物： 其中，R1至R4独立地表示H，卤素，OH，烷氧基，可选择取代的烷基，芳基或芳基烷基，R5表示H，可选择取代的烷基，芳基或芳基烷基，E1表示O，S或-NR6，其中R6表示H，可选择取代的烷基，芳基或芳基烷基，E2表示O，S或-NR7，其中R7表示H，可选择取代的烷基，芳基或芳基烷基，A表示CH，C（OH）或N，X表示H，卤素，烷氧基或可选择取代的烷基，Q表示可选择取代的苯基，苯氧基，苯甲基或环烷氧基，其中当E1表示O或S时，E2不表示O或S，该化合物具有抑制细胞毒性Ca2+过载和脂质过氧化作用，并且对于缓解和治疗缺血性疾病症状等方面的制药制剂具有有效作用。
• 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。
• Process for making N-((4-phenyl) methylphenyl) piperazines
  申请人：SUNTORY LIMITED

  公开号：EP1138678A2

  公开（公告）日：2001-10-04

  1. A process for producing a compound having the formula (XII'): wherein Q' represents an optionally substituted phenyl group and X represents a hydrogen atom, a halogen atom, an alkoxy group, or an optionally substituted alkyl group, that process comprises reacting a benzophenon derivative having the formula (XIII): wherein Q' and X are the same as defined above, and L represents a group which can be easily exchanged with an amino group, with a piperazine derivative having the formula (XIV): wherein W represents a hydrogen atom, a benzyl group, a p-methoxybenzyl group, a benzyloxycarbonyl group, a p-methoxybenzyloxycarbonyl group, a p-nitrobenzyloxycarbonyl group, a tert-butoxycarbonyl group, an ethoxycarbonyl group or an acetyl group to give a compound having the formula (XV): wherein Q', W and X are the same as defined above, and the subsequent reduction and deprotection of the compound having the formula (XV).

  1.一种生产具有式 (XII') 的化合物的工艺： 其中 Q'代表任选取代的苯基，X 代表氢原子、卤素原子、烷氧基或任选取代的烷基，该工艺包括使具有式 (XIII)： 其中 Q' 和 X 与上式定义相同，L 代表易于与氨基交换的基团，该工艺包括将具有式（XIV）的哌嗪衍生物与具有式（XIII）的苯甲酮衍生物反应： 其中 W 代表氢原子、苄基、对甲氧基苄基、苄氧羰基、对甲氧基苄氧羰基、对硝基苄氧羰基、叔丁氧羰基、乙氧羰基或乙酰基，得到式（XV）的化合物： 其中 Q'、W 和 X 与上文所定义的相同，随后对具有式（XV）的化合物进行还原和脱保护。
• 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。