PMID: 7830274Jan 20, 1995Paper

Evaluation of cis- and trans-9- and 11-hydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridines as structurally rigid, selective D1 dopamine receptor ligands

Journal of Medicinal Chemistry
W K BrewsterR B Mailman


The present study reports the investigation of the D1 structure-relationships of certain cis- or trans-9- or 11-monohydroxy analogues of (+/-)-trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a] phenanthridine (8a, dihydrexidine), previously identified as the first full efficacy D1 dopamine receptor agonist. The monohydroxybenzo[a]phenanthridines were prepared from the appropriately substituted beta-tetralones using the methods described earlier for the synthesis of their catechol analogues. The 10-bromo 11-hydroxy derivative 9e was prepared by treatment of precursor 9c with bromine in chloroform. The affinities of these compounds for the D1 and D2 dopamine receptor classes and for their effects on adenylate cyclase activity were assessed in rat striatal membranes. In addition to producing only minimal increases in adenylate cyclase activity (< or = 15%), these phenolic derivatives generally had significantly lower affinities for D1 and D2 receptors (D1 IC50 > or = 102 nM, D2 IC50 > or = 210 nM) than did their catechol analogues. Further, compounds bearing a cis B/C-ring fusion displayed lower affinities than those bearing a trans configuration, paralleling the activity differences between the catechol analogues. The data fo...Continue Reading


Apr 15, 2008·Archives of Pharmacal Research·Junghyun Chae
May 23, 2002·The Journal of Pharmacology and Experimental Therapeutics·David M MottolaRichard B Mailman
May 23, 2002·The Journal of Pharmacology and Experimental Therapeutics·Jason D KiltsRichard B Mailman
Aug 9, 2002·Journal of Medicinal Chemistry·Sing-Yuen SitGraham Johnson

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