2-(3,4-二氯苯基)-1-(2-(吡咯烷-1-甲基)哌啶-1-基)乙酮盐酸盐 | 130497-33-5

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(3,4-二氯苯基)-1-(2-(吡咯烷-1-甲基)哌啶-1-基)乙酮盐酸盐
• 中文别名: 2-(3,4-二氯苯基)-1-(2-(吡咯烷-1-基甲基)哌啶-1-基)乙酮盐酸盐
• 英文名称: [3H]-BRL 52537
• 英文别名: BRL 52537；1-<(3,4-dichlorophenyl)acetyl>-2-(1-pyrrolidinylmethyl)piperidine；BRL52537；2-(3,4-Dichlorophenyl)-1-[2-(1-pyrrolidinylmethyl)-1-piperidinyl]ethanone；2-(3,4-dichlorophenyl)-1-[2-(pyrrolidin-1-ylmethyl)piperidin-1-yl]ethanone
• CAS: 130497-33-5
• 化学式: C₁₈H₂₄Cl₂N₂O
• 分子量: 355.307
• InChiKey: GHCCBWMZKJQGLS-UHFFFAOYSA-N

物化性质

• 溶解度：
  在甲醇中可溶18 mg/mL at 60 °C, 可溶

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 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：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933990090

反应信息

• 作为产物：
  描述：

  1-[(3,4-二氯苯基)乙酰基]-2-哌啶甲醇 在 吡啶 、 chromium(VI) oxide 、 盐酸 、 3 A molecular sieve 、 sodium cyanoborohydride 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 73.0h， 生成 2-(3,4-二氯苯基)-1-(2-(吡咯烷-1-甲基)哌啶-1-基)乙酮盐酸盐
  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

• (2S)-1-(Arylacetyl)-2-(aminomethyl)piperidine derivatives: novel, highly selective .kappa. opioid analgesics
  作者：Vittorio Vecchietti、Antonio Giordani、Giuseppe Giardina、Roberto Colle、Geoffrey D. Clarke

  DOI：10.1021/jm00105a061

  日期：1991.1

  describes the synthesis and structure-activity relationships as kappa opioid analgesics of a novel class of 1-(arylacetyl)-2-(aminomethyl)piperidine derivatives. The active conformation of the pharmacophore, with a torsional angle (N1C2C7N8) of 60 degrees, was defined with computational studies and 1H NMR. A quantitative structure-activity relationship study of the arylacetic moiety substitution indicated

  本文描述了新型的1-（芳基乙酰基）-2-（氨基甲基）哌啶衍生物的合成和构效关系，作为κ阿片类镇痛药。通过计算研究和1H NMR定义了具有60度扭转角（N1C2C7N8）的药效团的活性构象。芳香族部分取代的定量结构-活性关系研究表明，对位和/或间位存在吸电子和亲脂性取代基是良好的镇痛活性和κ亲和力所必需的。铅化合物（2S）-1-[（（3,4-二氯苯基）乙酰基] -2-（吡咯烷-1-基甲基）哌啶盐酸盐和（2S）-1- [4-（三氟甲基）苯基]乙酰基] -2 -（吡咯烷-1-基甲基）哌啶盐酸盐的Kappa / mu选择性最高（分别为6500：1和4100：1）以及迄今为止鉴定出的最有力的（κκ0.24和0.57 nM）κ配体。在抗伤害感受的小鼠甩尾模型中，化合物14（ED50 = 0.05 mg / kg sc）的效力是吗啡的25倍，效力是标准Kappa配体U-50488的16倍。
• OPIOID RECEPTOR ANTAGONISTS
  申请人：Chappell Donald Mark

  公开号：US20070066658A1

  公开（公告）日：2007-03-22

  A compound of the formula (I) wherein the variables X 1 , X 2 , B, D, R 1 to R 7 including R 3′ , p, y, q, and z, are as defined or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed.

  本发明公开了一种式(I)的化合物，其中变量X1、X2、B、D、R1到R7包括R3'、p、y、q和z如定义所述，或其药学上可接受的盐、溶剂化物、对映体、外消旋体、对映异构体或其混合物，用于治疗、预防或缓解肥胖和相关疾病。
• Opioid Receptor Antagonists
  申请人：De La Torre Garcia Marta

  公开号：US20070287751A1

  公开（公告）日：2007-12-13

  A compound of the formula (I) wherein the variables X1, X2, R 1 to R 7 including R 3′ , j, k, p, y, and z, are as defined or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed.

  本发明揭示了一个化合物的公式（I），其中变量X1，X2，R1至R7包括R3'，j，k，p，y和z，如所定义，或其药学上可接受的盐，溶剂化物，对映体，外消旋体，非对映体异构体或其混合物，用于治疗，预防或缓解肥胖症和相关疾病。
• Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions
  申请人：Kõster Hubert

  公开号：US20100248264A1

  公开（公告）日：2010-09-30

  Capture compounds and collections thereof and methods using the compounds for the analysis of biomolecules are provided. In particular, collections, compounds and methods are provided for analyzing complex protein mixtures, such as the proteome. The compounds are multifunctional reagents that provide for the separation and isolation of complex protein mixtures. Automated systems for performing the methods also are provided.

  提供了捕获化合物及其集合以及使用这些化合物进行生物分子分析的方法。特别地，提供了用于分析复杂蛋白质混合物（如蛋白质组）的集合、化合物和方法。这些化合物是多功能试剂，可用于分离和分离复杂的蛋白质混合物。还提供了执行这些方法的自动化系统。
• Use of heterocyclic derivatives as kappa-opioid receptor agonists in the treatment of cerebral ischaemia
  申请人：GLAXO GROUP LIMITED

  公开号：EP0330468A2

  公开（公告）日：1989-08-30

  The invention relates to the use of certain heterocyclic compounds which act as kappa receptor agonists in the treatment of cerebral ischaemia.

  本发明涉及某些作为卡巴受体激动剂的杂环化合物在治疗脑缺血中的应用。