1-<(3,4-dichlorophenyl)acetyl>-3-hydroxy-2-(1-pyrrolidinylmethyl)piperidine | 125130-49-6

• 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: 1-<(3,4-dichlorophenyl)acetyl>-3-hydroxy-2-(1-pyrrolidinylmethyl)piperidine
• 英文别名: 1-(3,4-dichlorophenyl)acetyl-2-(pyrrolidin-1-yl)methyl-3-hydroxy piperidine；1-[(3,4-dichlorophenyl)acetyl]-2-(pyrrolidinylmethyl)-3-piperidinol；2-(3,4-Dichlorophenyl)-1-[3-hydroxy-2-(pyrrolidin-1-ylmethyl)piperidin-1-yl]ethanone
• CAS: 125130-49-6
• 化学式: C₁₈H₂₄Cl₂N₂O₂
• 分子量: 371.307
• InChiKey: PMJJKBYEMSFUBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-<(3,4-dichlorophenyl)acetyl>-3-hydroxy-2-(1-pyrrolidinylmethyl)piperidine 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 生成 1-<(3,4-dichlorophenyl)acetyl>-2-(1-pyrrolidinylmethyl)-3-piperidone
  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

• Piperidine derivatives
  申请人：GLAXO GROUP LIMITED

  公开号：EP0330461A2

  公开（公告）日：1989-08-30

  Compounds are disclosed of formula (I) wherein R₁ represents hydroxy, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ carboxyalkyl, phenyl, oxo, amino, carboxy, amido, -NR₄COR₅ (where R₄ and R₅ both represent C₁₋₆ alkyl), optionally substituted methylidene or, together with the carbon atom to which it is attached, R₁ forms a 5 or 6-membered ring containing one or more heteroatoms; R₂ and R₃ are the same or different and are C₁₋₆ alkyl or C₃₋₆ alkenyl; or -NR₂R₃ forms a 5-membered (optionally containing an oxygen atom adjacent to the nitrogen) or a 6-membered ring, which ring optionally contains one unit of unsaturation and which is unsubstituted or substituted by hydroxy, oxo, optionally substituted methylidene, -COR₆ (where R₆ represents C₁₋₆ alkyl, OR₇ or -NHR₇, and R₇ represents hydrogen, C₁₋₆ alkyl, aryl, ar(C₁₋₆)alkyl) or =NOR₈ (where R₈ represents C₁₋₆ alkyl); X represents a direct bond, -CH₂- or -CH₂O-; Ar represents a substituted phenyl moiety; and physiologically acceptable salts thereof. The compounds are indicated as useful for the treatment of pain and cerebral ischaemia. Processes and intermediates for their preparation and pharmaceutical compositions containing them are also disclosed.

  公开了式(I)化合物 其中 R₁ 代表羟基、C₁₋₆ 烷基、C₁₋₆ 羟基烷基、C₁₋₆ 羧基烷基、苯基、氧代、氨基、羧基、氨基、-NR₄COR₅（其中 R₄ 和 R₅ 均代表 C₁₋₆ 烷基）、任选取代的亚甲基，或 R₁ 与所连接的碳原子一起形成含有一个或多个杂原子的 5 或 6 元环； R₂ 和 R₃ 相同或不同，并且是 C₁₋₆ 烷基或 C₃₋₆ 烯基；或-NR₂R₃形成一个 5 元环（可选含有一个与氮相邻的氧原子）或一个 6 元环，该环可选含有一个不饱和单元，且该环未被羟基、氧代取代或被羟基、氧代取代、任选取代的亚甲基、-COR₆（其中 R₆ 代表 C₁₋₆ 烷基、OR₇ 或 -NHR₇，且 R₇ 代表氢、C₁₋₆ 烷基、芳基、ar(C₁₋₆)烷基）或 =NOR₈ （其中 R₈ 代表 C₁₋₆ 烷基）； X 代表直接键、-CH₂- 或 -CH₂O-； Ar 代表取代的苯基； 及其生理上可接受的盐类。 这些化合物可用于治疗疼痛和脑缺血。 此外，还公开了制备这些化合物的工艺和中间体以及含有这些化合物的药物组合物。
• PHARMACEUTICALS
  申请人：SMITHKLINE BEECHAM FARMACEUTICI S.p.A.

  公开号：EP0574477A1

  公开（公告）日：1993-12-22
• US5114945A
  申请人：——

  公开号：US5114945A

  公开（公告）日：1992-05-19
• 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.