Synthesis, opioid receptor binding, and functional activity of 5′-substituted 17-cyclopropylmethylpyrido[2′,3′:6,7]morphinans

A series of naltrexone-derived pyridomorphinans possessing various substituents at the 5'-position on the pyridine ring were synthesized and evaluated for opioid receptor binding in rodent brain membranes and functional activity in smooth muscle preparations. While the introduction of aromatic I-pyrrolyl group (6h) improved the 8 affinity and 6 antagonist potency of the parent compound (3), the introduction of guanidine group (6i) transformed it to a K selective ligand in opioid receptor binding and [S-35]GTP-gamma-S functional assays. (C) 2002 Elsevier Science Ltd. All rights reserved.