6β-acrylamido-17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan | 83339-84-8

• 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: 6β-acrylamido-17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan
• CAS: 83339-84-8
• 化学式: C₂₃H₂₈N₂O₄
• 分子量: 396.486
• InChiKey: TVKTWELUOXKCHA-HJARAHSNSA-N

反应信息

• 作为产物：
  描述：

  、 丙烯酰氯 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 20.0h， 以79%的产率得到6β-acrylamido-17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan
  参考文献：
  名称：

  Importance of carbon 6 chirality in conferring irreversible opioid antagonism to naltrexone-derived affinity labels

  摘要：

  A series of five epimeric pairs of naltrexone derivatives that contain an electrophilic substituent at the 6 alpha- or 6 beta-position was synthesized and tested on the guinea pig ileal longitudinal muscle (GPI) and mouse vas deferens (MVD) preparations in order to determine if the orientation of the electrophile is important for covalent bonding to opioid receptors. In the GPI all compounds were pharmacologically active as reversible agonists, but only the 6 beta-isomers of the fumaramate ester 2b (beta-FNA) and isothiocyanate 6b exhibited covalent reactivity, involving a selective irreversible antagonism of the mu agonist, morphine, without affecting kappa agonists. The 6 alpha-isomer 2a (alpha-FNA) was itself nonalkylating but was able to protect the GPI against alkylation by its epimer, beta-FNA, indicating that the two epimers bind to the same receptor. These results suggest that the proper orientation of the electrophilic substituent is required for covalent bonding with a proximal nucleophile in the case of mu receptor blockade. Moreover, the lack of covalent bonding to kappa receptors by these or other ligands in this series indicates the possible absence of sufficiently reactive nucleophiles on this recognition site. In the MVD, 2b, but not 2a, irreversibly antagonized morphine (as in GPI), whereas neither epimer exhibited irreversible antagonism toward the delta agonist, [D-Ala2,D-Leu5]enkephalin (DADLE). In contrast, both of the isothiocyanate epimers (6a,b) irreversibly blocked mu and delta receptors. Evidence suggesting differences between mu receptors in the MVD and GPI was obtained with the beta-iodoacetamide 5b, which was an irreversible blocker of morphine only in the MVD. When analyzed together with those of previous studies with the nitrogen mustard analogues, alpha- and beta-chlornaltrexamine, the data suggest that the receptor-alkylating ability of each isomer in an epimeric pair differs most when the electrophile possesses a narrow spectrum of reactivity.

  DOI：

  10.1021/jm00363a005