High affinity binding for mu and kappa opioid receptors has been observed in analogues of cyclazocine, ethylketocyclazocine and naltrexone where the prototypic (of opiates) phenolic OH group was replaced with a formamide (-NHCHO) group. For the 8-formamide analogue of cyclazocine, binding is highly enantiospecific (eudismic ratios approximately 2000 for mu and kappa) with K(i) values =1 nM observed for the (2R,6R,11R)-isomer, (-)-4. A preliminary SAR revealed that affinity is very sensitive to substitution on the formamide appendage.
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http://dx.doi.org/10.1016/s0960-894x(03)00295-6 | DOI Listing |
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