14C-17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4'-bromo)benzamido]morphinan | 1192546-47-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 14C-17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4'-bromo)benzamido]morphinan
• 英文别名: N-[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-4-bromo(14C)benzamide
• CAS: 1192546-47-6
• 化学式: C₂₇H₂₉BrN₂O₄
• 分子量: 527.431
• InChiKey: XEQUQWJVHIEWQA-HTRQLCALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  82
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  14C1-p-bromobenzoic acid 、 (5alpha,6beta)-6-氨基-17-(环丙基甲基)-4,5-环氧-吗喃-3,14-二醇 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 potassium carbonate 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 5.0h， 以91%的产率得到14C-17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4'-bromo)benzamido]morphinan
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of 6-naltrexamine analogs for alcohol cessation

  摘要：

  A series of substituted aryl amide derivatives of 6-naltrexamine, 3 designed to be metabolically stable were synthesized and used to characterize the structural requirements for their potency to binding and functional activity of human mu (mu), delta (delta) and kappa (kappa) opioid and nociceptin (NOP) receptors. Binding assays showed that 4-10 had subnanomolar K-i values for mu and kappa opioid receptors. Functional assays for stimulation of [S-35] GTP gamma S binding showed that several compounds acted as partial or inverse agonists and antagonists of the mu and delta, kappa opioid or NOP receptors. The compounds showed considerable stability in the presence of rat, mouse or human liver preparations and NADPH. The inhibitory activity on the functional activity of human cytochrome P450s was examined to determine any potential inhibition by 4-9. Only modest inhibition of CYP3A4, CYP2C9 and CYP2C19 was observed for a few of the analogs. As a representative example, radiolabeled 6 was examined in vivo and showed reasonable brain penetration. The inhibition of ethanol self-administration in rats trained to self-administer a 10% (w/v) ethanol solution, utilizing operant techniques showed 5-8 to have very potent efficacy (ED50 values 19-50 mu g/kg). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.069