4-{4-[(4-Benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-piperidin-1-yl}-butan-2-ol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-{4-[(4-Benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-piperidin-1-yl}-butan-2-ol
• 英文别名: 4-[4-[N-(3-methylbut-2-enyl)-4-phenylmethoxyanilino]piperidin-1-yl]butan-2-ol
• 化学式: C₂₇H₃₈N₂O₂
• 分子量: 422.611
• InChiKey: JFXBOAMVDBHSQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  35.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-(4-benzyloxy-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 36.67h， 生成 4-{4-[(4-Benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-piperidin-1-yl}-butan-2-ol
  参考文献：
  名称：

  The discovery of [1-(4-dimethylamino-benzyl)-piperidin-4-yl]-[4-(3,3-dimethylbutyl)-phenyl]-(3-methyl-but-2-enyl)-amine, an N-type Ca +2 channel blocker with oral activity for analgesia

  摘要：

  Our drug discovery efforts for N-type calcium channel blockers in the 4-piperidinylaniline series led to the discovery of an orally active analgesic agent 26. 1-[4-Dimethylamino-benzyl)-piperidin-4-yl]-[4-(3,3-dimethyl-butyl)-phenyl]-(3-methyl-but-2-enyl)-amine (26) showed high affinity to functionally block N-type calcium channels IC50 = 0.7 mu M in the IMR32 assay) and exhibited high efficacy in the anti-writhing analgesia test with mice (ED50 = 12 mg/kg by po and 4 mg/kg by iv). In this report, the rationale for the design, synthesis, biological evaluation, and pharmacokinetics of this series of blockers is described. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00077-8

文献信息

• [EN] HETEROCYCLIC SUBSTITUTED ANILINE CALCIUM CHANNEL BLOCKERS<br/>[FR] AGENTS D'ANILINE HETEROCYCLIQUE SUBSTITUEE BLOQUANT LES CANAUX DE CALCIUM
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1999043658A1

  公开（公告）日：1999-09-02

  (EN) The present invention provides compounds that block calcium channels having Formula (I): wherein each n is independently 0 to 3; R1 is C1-C8 alkyl, substituted C1-C8 alkyl, C3-C8 cycloalkyl, substituted C3-C8 cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, C2-C8 alkenyl, C3-C8 cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or arylalkyl; Y is (a), (b), (c), (d), (e), (f), (g) or (h); X is C1-C8 alkyl, C1-C8 substituted alkyl, C2-C8 alkenyl, C2-C8 substituted alkenyl, arylalkyl, substituted arylalkyl, heteroarylalkyl, substituted heteroarylalkyl, cycloalkylalkyl, or substituted cycloalkylalkyl; R2 is absent, -O-, (CH2)n-, O(CH2)n-, (CH2)nO-, N(R5)(CH2)n-, (CH2)nN(R5)-, S(CH2)n-, (CH2)nS-, -C=C-, or -C$m(Z)C-; R3 is monocyclic aryl, substituted monocyclic aryl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, C1-C8 alkyl, substituted C1-C8 alkyl, C3-C10 cycloalkyl, substituted C3-C10 cycloalkyl; R4, R5 are independently H or C1-C8 alkyl. The present invention also provides methods of using the compounds of Formula (I) to treat stroke, cerebral ischemia, head trauma, epilepsy, asthma, amyotrophic lateral sclerosis, or pain and to pharmaceutical compositions that contain the compounds of Formula (I).(FR) L'invention concerne des composés qui bloquent les canaux de calcium ayant la formule (I) où chaque n vaut indépendamment 0 à 3; R1 représente alkyle C1-C8, alkyle C1-C8 substitué, cycloalkyle C3-C8, cycloalkyle C3-C8 substitué, hétérocycloalkyle, hétérocycloalkyle substitué, alcényle C2-C8, cycloalcényle C3-C8, aryle, aryle substitué, hétéroaryle, hétéroaryle substitué ou arylalkyle; Y représente (a), (b), (c), (d), (e), (f), (g) ou (h); X représente alkyle C1-C8, alkyle C1-C8 substitué, alcényle C2-C8, alcényle C2-C8 substitué, ayrylalkyle, arylalkyle substitué, hétéroarylalkyle, hétéroarylalkyle substitué, cycloalkylalkyle ou cycloalkylalkyle substitué; R2 est absent, -O-, (CH2)n-, O(CH2)n-, (CH2)nO-, N(R5)(CH2)n-, (CH2)nN(R5)-, S(CH2)n-, (CH2)nS-, -C=C-, ou -C$m(Z)C-; R3 représente de l'aryle monocyclique, aryle monocyclique substitué, hétéroaryle, hétéroaryle substitué, alkyle C1-C8 hétérocyclique, hétérocyclique substitué, alkyle C1-C8 substitué, cycloalkyle C3-C10, cycloalkyle C3-C10 substitués; R4, R5 représentent indépendamment H ou alkyle C1-C8. La présente invention concerne également des procédés d'utilisation des composés de la formule (I) pour traiter les accidents cérébrovasculaires, l'ischémie cérébrale, les traumatismes crâniens, l'épilepsie, l'asthme, la sclérose latérale amyotrophique ou des douleurs et pour préparer des compositions pharmaceutiques contenant les composés de la formule (I).

  本发明提供了具有式（I）的阻断钙通道的化合物，其中每个n独立地为0至3；R1为C1-C8烷基，取代C1-C8烷基，C3-C8环烷基，取代C3-C8环烷基，杂环烷基，取代杂环烷基，C2-C8烯基，C3-C8环烯基，芳基，取代芳基，杂芳基，取代杂芳基或芳基烷基；Y为（a），（b），（c），（d），（e），（f），（g）或（h）；X为C1-C8烷基，C1-C8取代烷基，C2-C8烯基，C2-C8取代烯基，芳基烷基，取代芳基烷基，杂芳基烷基，取代杂芳基烷基，环烷基烷基或取代环烷基烷基；R2缺失，-O-，（CH2）n-，O（CH2）n-，（CH2）nO-，N（R5）（CH2）n-，（CH2）nN（R5）-，S（CH2）n-，（CH2）nS-，-C = C-或-C $ m（Z）C-；R3为单环芳基，取代单环芳基，杂芳基，取代杂芳基，杂环，取代杂环，C1-C8烷基，取代C1-C8烷基，C3-C10环烷基，取代C3-C10环烷基；R4，R5独立地为H或C1-C8烷基。本发明还提供了使用式（I）的化合物治疗中风，脑缺血，头部创伤，癫痫，哮喘，肌萎缩性脊髓侧索硬化或疼痛的方法，并提供含有式（I）的制药组合物。
• US6251919B1
  申请人：——

  公开号：US6251919B1

  公开（公告）日：2001-06-26
• The discovery of [1-(4-dimethylamino-benzyl)-piperidin-4-yl]-[4-(3,3-dimethylbutyl)-phenyl]-(3-methyl-but-2-enyl)-amine, an N-type Ca +2 channel blocker with oral activity for analgesia
  作者：Lain-Yen Hu、Todd R. Ryder、Michael F. Rafferty、Charles P. Taylor、M.Rose Feng、Be-Sheng Kuo、Susan M. Lotarski、George P. Miljanich、Elizabeth Millerman、Krista M. Siebers、Balazs G. Szoke

  DOI：10.1016/s0968-0896(00)00077-8

  日期：2000.6

  Our drug discovery efforts for N-type calcium channel blockers in the 4-piperidinylaniline series led to the discovery of an orally active analgesic agent 26. 1-[4-Dimethylamino-benzyl)-piperidin-4-yl]-[4-(3,3-dimethyl-butyl)-phenyl]-(3-methyl-but-2-enyl)-amine (26) showed high affinity to functionally block N-type calcium channels IC50 = 0.7 mu M in the IMR32 assay) and exhibited high efficacy in the anti-writhing analgesia test with mice (ED50 = 12 mg/kg by po and 4 mg/kg by iv). In this report, the rationale for the design, synthesis, biological evaluation, and pharmacokinetics of this series of blockers is described. (C) 2000 Elsevier Science Ltd. All rights reserved.