Analgesic 1-oxidized-2,6-methano-3-benzazocines

Abstract

g, 0.269 mole), SOjClj (302 g, 2.24 mole), and 200 ml of C6H6 were refluxed for 16 hr. The C6H6 was distd off. Recrystn from C6H6-C6HJ4 gave 75.0 g (86%) of 4,4',6,6'-tetrachloro-2,2'-diphenol, mp 166-172°, lit.21 mp 178'.

Syntheses of 10-Oxo, 10.ALPHA.-Hydroxy, and 10.BETA.-Hydroxy Derivatives of a Potent .KAPPA.-Opioid Receptor Agonist, TRK-820

“…10,12) A similar stereoselectivity of 10-oxo hydride reduction was observed by reduction of model compound 17 (Chart 3). Stereochemistry of the resulting compound 21 was analyzed by NOESY and COSY spectra, and positive NOE signal was observed between the 8-axial proton and the 10-position proton.…”

“…On the other hand, some k-opioid selective ligands like ketocyclazocine 7 12) and ethylketocyclazocine 8 13) have an oxo group in common on their benzylic positions. Furthermore, it was described that introduction of an oxo group at the 10-position of KT-90 9, 14) a k-opioid agonist, gave KT-95 10 15) which exhibited higher analgesic activity and affinity to k-opioid receptor than those of (Fig.…”

Synthesis and reactions of 1,2,3,4,5,6-hexahydro-3,6-dimethyl-2,6-methano-3-benzazocin-11-one (2,5-dimethyl-9-oxo-6,7-benzomorphan); a new route to 3-benzazocines

“…ref. 37). Compared with our maximum yield of only 29% (see * We thank Professor R. T. Parfitt, University of Bath, for advice on this procedure.…”

Structure of a κ-opioid receptor misfit: (1S,5R,8R,9R)-2'-hydroxy-5,9-dimethyl-8,2-epoxyethano-6,7-benzomorphan hydrochloride

“…A 2'-methoxy analogue lacking the 9-methyl group was reported to be inactive (Shiotani & Kometani, 1980). Other modifications of the structure of ketazocine, such as the replacement of the carbonyl by an equatorial hydroxy or methoxy group with retention of the N-cyclopropylmethyl [Michne & Albertson (1972) and Merz (1983), respectively] led also to inactive compounds. In 1984 a model was proposed to explain x-opioid activity in the 6,7-benzomorphan series, establishing a distinct role for this crucial O atom (De Ranter, Verlinde, Blaton & Peeters, 1984).…”