Facile synthesis of octahydrobenzo[h]isoquinolines: novel and highly potent D1 dopamine agonists.
The octahydrobenzo[h]isoquinoline scaffold is of interest as a conformationally-restricted phenethylamine that may be useful for constructing biologically active products. Surprisingly, however, no tractable synthesis of this ring system has been reported. We now describe a facile method for obtaining this framework, and illustrate that our approach is easily amenable to substitutions at the 5-position. Importantly, we demonstrate that the 7,8-dihydroxy-5-phenyl-substituted ligand is an extremely potent, high-affinity, full D1 dopamine receptor-selective agonist.
Bonner
Lisa A
LA
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, United States.
Chemel
Benjamin R
BR
Watts
Val J
VJ
Nichols
David E
DE
D000818:Animals; D001665:Binding Sites; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D010627:Phenethylamines / Q000737:chemistry; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000378:metabolism; D013552:Swine
C516224:2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno(3,4-c)isoquinoline; D007546:Isoquinolines; D010617:Phenanthridines; D010627:Phenethylamines; D017447:Receptors, Dopamine D1; C029261:phenethylamine