Benjamin R. Chemel J.I. Juncosa Jr. M.A. Lill V.J. Watts D.E. Nichols J.P. Cueva 2012 <p><span>Efforts to develop selective&nbsp;agonists&nbsp;for&nbsp;dopamine&nbsp;D</span>₁<span>-like receptors led to the discovery of dihydrexidine and doxanthrine, two bioisosteric β-phenyldopamine-type full agonist ligands that display selectivity and potency at D</span>₁<span>-like receptors. We report herein an improved methodology for the synthesis of substituted chromanoisoquinolines (doxanthrine derivatives) and the evaluation of several new compounds for their ability to bind to D</span>₁<span>- and D</span>₂<span>-like receptors. Identical pendant phenyl ring substitutions on the dihydrexidine and doxanthrine templates surprisingly led to different effects on D</span>₁<span>-like receptor binding, suggesting important differences between the interactions of these ligands with the D</span>₁<span>&nbsp;receptor. We propose, based on the biological results and&nbsp;molecular modeling&nbsp;studies, that slight conformational differences between the&nbsp;tetralin&nbsp;and chroman-based compounds lead to a shift in the location of the pendant ring substituents within the receptor.</span></p> application/pdf 10.1016/j.ejmech.2011.11.039 en Elsevier Analogues of doxanthrine reveal differences between the dopamine D1 receptor binding properties of chromanoisoquinolines and hexahydrobenzo[a]phenanthridines article