Table 1. Structures, Binding Affinities and Selectivities for the μ-OR, and Antinociceptive Potencies of Oxymorphone (1) and Investigated 14-Oxygenated N-Methylmorphinan-6-ones (2–6)^a.

		in vitro μ-OR bindingc
ligand	R1, R2b	μ-OR affinity (Ki, nM)	μ-OR selectivity vs δ-OR	μ-OR selectivity vs κ-OR	antinociceptive potencyd
OM (1)	H, H	0.97	83	63	13,e 18,f 10g
14-OMO (2a)	Me, H	0.10	48	102	810,e 300,f 126,g
14-MM (2b)	Me, Me	0.15	89	168	99,e 82,f 94g
14-OEO (3a)	Et, H	0.15	60	91	316e
14-EM (3b)	Et, Me	0.46	26	94	46e
14-OBO (4a)	Bz, H	0.12	18	10	697g
14-BM (4b)	Bz, Me	0.18	20	14	103g
PPOM (5)	PhPr, Me	0.20	0.7	2	2500,e 24000,f 8500g
BOMO (6)	Me, Bz	0.31	42	73	53,f 50g

^aData reviewed in refs (8) and (9).

^bBz, benzyl; Et, ethyl; Me, methyl; PhPr, phenylpropyl.

^cDetermined by in vitro radioligand binding assays with rat brain membranes.

^dRelative to morphine, determined in mice after s.c. administration using the indicated tests.

^eAcetic acid-induced writhing test.

^fTail-flick test.

^gHot-plate test.