Z-2-<<3-(cyanomethylene)-1-pyrrolidinyl>methyl>-1-<(3,4-dichlorophenyl)acetyl>piperidine | 125348-58-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Z-2-<<3-(cyanomethylene)-1-pyrrolidinyl>methyl>-1-<(3,4-dichlorophenyl)acetyl>piperidine
• 英文别名: (1-{1-[2-(3,4-Dichloro-phenyl)-acetyl]-piperidin-2-ylmethyl}-pyrrolidin-3-ylidene)-acetonitrile；(2Z)-2-[1-[[1-[2-(3,4-dichlorophenyl)acetyl]piperidin-2-yl]methyl]pyrrolidin-3-ylidene]acetonitrile
• CAS: 125348-58-5
• 化学式: C₂₀H₂₃Cl₂N₃O
• 分子量: 392.328
• InChiKey: WKJMMBKITNREGG-UUASQNMZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3,4-二氯苯乙酸 在 吡啶 、 chromium(VI) oxide 、 盐酸 、 草酰氯 、 3 A molecular sieve 、 sodium hydride 、 sodium cyanoborohydride 、 二甲基亚砜 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 81.67h， 生成 Z-2-<<3-(cyanomethylene)-1-pyrrolidinyl>methyl>-1-<(3,4-dichlorophenyl)acetyl>piperidine
  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

• New .kappa.-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus
  作者：David I. C. Scopes、Norman F. Hayes、David E. Bays、David Belton、John Brain、Dearg S. Brown、Duncan B. Judd、Andrew B. McElroy、Clive A. Meerholz

  DOI：10.1021/jm00081a009

  日期：1992.2

  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.