(R)-(-)-N-(cyclopropylmethyl)norapomorphine | 18426-18-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: (R)-(-)-N-(cyclopropylmethyl)norapomorphine
• 英文别名: 6-Cyclopropylmethyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol; hydrochloride；(6aR)-6-(cyclopropylmethyl)-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol
• CAS: 18426-18-1
• 化学式: C₂₀H₂₁NO₂
• 分子量: 307.392
• InChiKey: OXQZCFBTWSWVNN-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (R)-(-)-N-(cyclopropylmethyl)norapocodeine hydrochloride 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-(-)-N-(cyclopropylmethyl)norapomorphine
  参考文献：
  名称：

  Synthesis and structural requirements of N-substituted norapomorphines for affinity and activity at dopamine D-1, D-2, and agonist receptor sites in rat brain

  摘要：

  A series of N-substituted analogues of (R)-(-)-norapomorphine were synthesized to study the optimal structural requirements of the N-alkyl side chain to interact with D-1 and D-2 dopaminergic receptors as well as dopamine (DA) agonist binding sites. Evaluations included testing the affinity of these compounds for DA receptor sites in rat striatal tissue and assessing stereotypy as a behavioral index of dopaminergic activity. The electronic, steric, and lipophilic properties of the N-alkyl side chain were found to be related to affinity, D-2 selectivity, and dopaminergic activity. All 11 compounds evaluated had relatively low affinity at D-1 sites. Optimum D-2 and agonist-site affinity as well as agonist activity were exhibited by N-cyclopropylmethyl (7) greater than or equal to N-allyl (8) greater than or equal to N-propyl (4) or N-ethyl (3) substituted compounds. Branching of the N-alkyl side chain as in N-isopropyl (5) and N-isobutyl (6) markedly reduced the D-2 affinity and activity, presumably due to steric effects. The N-trifluoroethyl (10) and N-pentafluoropropyl (11) derivatives had low affinity for all their dopamine receptor sites and no agonistic activity; evidently, the highly electronegative F atoms decrease basicity of the N atom and therefore decrease the ability of the N atom to be cationic at physiological pH, a proposed requirement for high-affinity binding to DA receptors.

  DOI：

  10.1021/jm00163a007