8-<(3,4-dichlorophenyl)acetyl>-7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro<4.5>decane | 138154-97-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 8-<(3,4-dichlorophenyl)acetyl>-7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro<4.5>decane
• 英文别名: 8-[(3,4-Dichlorophenyl)acetyl]-7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro[4.5]decane；8-[(3,4-Dichlorophenyl)acetyl]-7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-aza[4.5]spirodecane；2-(3,4-Dichloro-phenyl)-1-(7-pyrrolidin-1-ylmethyl-1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-ethanone；2-(3,4-dichlorophenyl)-1-[7-(pyrrolidin-1-ylmethyl)-1,4-dioxa-8-azaspiro[4.5]decan-8-yl]ethanone
• CAS: 138154-97-9
• 化学式: C₂₀H₂₆Cl₂N₂O₃
• 分子量: 413.344
• InChiKey: LWUQHEXXEFUHHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-<(3,4-dichlorophenyl)acetyl>-7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro<4.5>decane 在 aluminum oxide 、 sodium tetrahydroborate 、 硫酸 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 41.5h， 生成 1-<(3,4-dichlorophenyl)acetyl>-4-oxo-2-(1-pyrrolidinylmethyl)piperidine hydrochloride
  参考文献：
  名称：

  New .kappa.-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus

  摘要：

  The syntheses of some 1-[(3,4-dichlorophenyl)acetyl]2-[(alkylamino)methyl]peperidines and their activities as kappa-opioid receptor agonists are described. Selected structural modifications are made to the basic moiety and at the 2-, 3-, 4-, 5-, and 6-positions on the piperidine nucleus to enable structure-activity relationships to be delineated. As a result, some highly potent and selective kappa-receptor agonists have been identified. In particular, this has been achieved by introduction of oxygen-containing functionality into the 4-position of the piperidine nucleus or the 3-position of the pyrrolidinylmethyl side chain. Thus, 1-[(3,4-dichlorophenyl)acetyl]2-[[1-(3-oxopyrrolidinyl)methyl]?? piperidine (10) possesses high activity in the rabbit vas deferens (LCD, kappa-specific tissue) (IC50 = 0.20 nM) and is a potent antiociceptive agent, as determined by the mouse acetylcholine-induced abdominal constriction test (MAC) (ED50 = 0.06 mg/kg sc). The spirocyclic analogue 8-[3,4-dichlorophenyl)acetyl]7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro[4.5]decane (39) showed exceptionally potent activity: LVD, IC50 = 0.10 nM; MAC, ED50 = 0.001 mg/kg, sc. Both 10 and 39 displayed high selectivity for kappa-opioid receptors over both mu- and delta-opioid receptor subtypes.

  DOI：

  10.1021/jm00081a009
• 作为产物：
  描述：

  7-methyl 8-(phenylmethyl) 1,4-dioxa-8-azaspiro<4.5>decane-7,8-dicarboxylate 在 palladium on activated charcoal lithium aluminium tetrahydride 、 氢气 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 30.0h， 生成 8-<(3,4-dichlorophenyl)acetyl>-7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro<4.5>decane
  参考文献：
  名称：

  New .kappa.-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus

  摘要：

  The syntheses of some 1-[(3,4-dichlorophenyl)acetyl]2-[(alkylamino)methyl]peperidines and their activities as kappa-opioid receptor agonists are described. Selected structural modifications are made to the basic moiety and at the 2-, 3-, 4-, 5-, and 6-positions on the piperidine nucleus to enable structure-activity relationships to be delineated. As a result, some highly potent and selective kappa-receptor agonists have been identified. In particular, this has been achieved by introduction of oxygen-containing functionality into the 4-position of the piperidine nucleus or the 3-position of the pyrrolidinylmethyl side chain. Thus, 1-[(3,4-dichlorophenyl)acetyl]2-[[1-(3-oxopyrrolidinyl)methyl]?? piperidine (10) possesses high activity in the rabbit vas deferens (LCD, kappa-specific tissue) (IC50 = 0.20 nM) and is a potent antiociceptive agent, as determined by the mouse acetylcholine-induced abdominal constriction test (MAC) (ED50 = 0.06 mg/kg sc). The spirocyclic analogue 8-[3,4-dichlorophenyl)acetyl]7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro[4.5]decane (39) showed exceptionally potent activity: LVD, IC50 = 0.10 nM; MAC, ED50 = 0.001 mg/kg, sc. Both 10 and 39 displayed high selectivity for kappa-opioid receptors over both mu- and delta-opioid receptor subtypes.

  DOI：

  10.1021/jm00081a009

文献信息

• ANTIPRURITIC AGENT
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP0897726A1

  公开（公告）日：1999-02-24

  An antipruritic agent comprising as the active ingredient an opioid k receptor agonist useful for the treatment of pruritus in various diseases accompanied by pruritus, and novel morphinane quaternary ammonium salt derivatives and morphinane N-oxide derivatives.

  一种止痒剂，其活性成分包括一种阿片 k 受体激动剂，可用于治疗伴有瘙痒的各种疾病中的瘙痒症，以及新型吗啡烷季铵盐衍生物和吗啡烷 N-氧化物衍生物。
• REMEDIES FOR DRUG ADDICTION
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP0974363A1

  公开（公告）日：2000-01-26

  Remedies for drug addiction which contain as the active ingredient k-opioid receptor agonists typified by the compounds represented by general formula (I). These k-opioid receptor agonists are useful as remedies for drug addiction which are reduced in side effects and act on the reward effect expression mechanism so as to inhibit the expression of mental addiction and physical addiction simultaneously, different from the symptomatic therapy conventionally employed in treating drug addiction.

  治疗毒瘾的药物，其有效成分为 k-阿片受体激动剂，通式(I)代表的化合物是其典型代表。这些 k-阿片受体激动剂作为治疗药物成瘾的药物，副作用小，作用于奖赏效应表达机制，从而同时抑制精神成瘾和身体成瘾的表达，不同于传统的治疗药物成瘾的对症疗法。
• Antipruritic agent
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP1310255A1

  公开（公告）日：2003-05-14

  This invention provides an antipruritic comprising an opiate K receptor agonist as an effective component, and morphinian derivatives which are useful for the treatment of pruritus caused by various diseases.

  本发明提供了一种止痒剂，其中包括作为有效成分的阿片类 K 受体激动剂和吗啡衍生物，可用于治疗各种疾病引起的瘙痒症。
• REMEDIES FOR PSYCHONEUROSIS
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP1380306A1

  公开（公告）日：2004-01-14

  A therapeutic drug for psychoneurotic disorders, which is useful for therapies of psychoneurotic disorders, especially restless legs syndrome is disclosed. The therapeutic drug for psychoneurotic disorders according to the present invention comprises as an effective ingredient an opioid κ receptor agonist compound (excluding pentazocine) such as (-)-17-(cyclopropylmethyl)-3,14β-dihydroxy-4,5α-epoxy-6β[N-methyl-trans-3-(3-furyl)acrylamide]morphinan hydrochloric acid salt.

  本发明公开了一种精神神经障碍治疗药物，可用于治疗精神神经障碍，尤其是不宁腿综合征。根据本发明，用于精神神经障碍的治疗药物包括作为有效成分的阿片类κ受体激动剂化合物（不包括喷他佐辛），如(-)-17-(环丙基甲基)-3,14β-二羟基-4,5α-环氧-6β[N-甲基-反式-3-(3-呋喃基)丙烯酰胺]吗啡南盐酸盐。
• Remedies for psychoneurosis
  申请人：——

  公开号：US20040116456A1

  公开（公告）日：2004-06-17

  A therapeutic drug for psychoneurotic disorders, which is useful for therapies of psychoneurotic disorders, especially restless legs syndrome is disclosed. The therapeutic drug for psychoneurotic disorders according to the present invention comprises as an effective ingredient an opioid &kgr; receptor agonist compound (excluding pentazocine) such as (−)-17-(cyclopropylmethyl)-3,14&bgr;-dihydroxy-4,5&agr;-epoxy-6&bgr;[N-methyl-trans-3-(3-furyl)acrylamide]morphinan hydrochloric acid salt.

  本发明公开了一种精神神经障碍治疗药物，可用于治疗精神神经障碍，尤其是不宁腿综合征。根据本发明，用于精神神经障碍的治疗药物包括作为有效成分的阿片受体激动剂化合物（不包括喷他佐辛），如(-)-17-(环丙基甲基)-3,14&bgr;-二羟基-4,5&agr;-环氧-6&bgr;[N-甲基-反式-3-(3-呋喃基)丙烯酰胺]吗啡南盐酸盐。