6199-38-8Relevant academic research and scientific papers
Opioid affinity and selectivity of 4-hydroxy-3-methoxyindolomorphinan analogues related to naltrindole
Coop, Andrew,Rothman, Richard B.,Dersch, Christina,Partilla, John,Porreca, Frank,Davis, Peg,Jacobson, Arthur E.,Rice, Kenner C.
, p. 1673 - 1679 (1999)
To investigate the effect of the introduction of a 4-phenolic substituent on the δ opioid affinity and selectivity of the indolomorphinans, a range of 4-phenolic analogues of naltrindole were prepared and evaluated in in vitro assays. Although the majority of the ligands displayed poor affinity for all three opioid receptors (μ, κ, δ), 17-cyclopropylmethyl-6,7-didehydro-4-hydroxy-3-methoxy-6,7:2',3'- indolomorphinan (13) was an exception, displaying excellent 5 binding selectivity (δ K(i) = 7 nM, μ/δ = 1900, μ/κ = 1130). GTP-χ-S functional assays showed 13 to be a selective δ antagonist, albeit with lower potency than naltrindole. Although the reason for the unique profile of 13 could not be determined, these results validate our approach of introducing groups into the indolomorphinans that are known to reduce μ activity, to obtain increased δ selectivity.
Rapid access to morphinones: removal of 4,5-ether bridge with Pd-catalyzed triflate reduction
Hupp, Christopher D.,Neumeyer, John L.
supporting information; experimental part, p. 2359 - 2361 (2010/06/13)
A new synthetic method for the removal of the 4,5-bridged ether moiety of several opioids has been developed. This process offers a faster, simpler synthetic route to obtain the morphinone scaffold in high yields without the need for protection of the ketone moiety.
Synthesis and opioid receptor activity of indolopropellanes
Li, Fuying,Gaob, Linghuan,Yin, Chenlei,Chen, Jie,Liu, Jinggen,Xie, Xin,Zhang, Ao
scheme or table, p. 4603 - 4606 (2010/04/29)
A series of skeletal rearranged indolomorphinans 7a-d were obtained by N-demethylation of 3-methoxy-N-methyl-14-hydroxymorphinan-6-one 12 followed by N-realkylation, reduction and Fischer indole cyclization. The structure of the novel skeleton was confirmed by X-ray analysis. These new indoles displayed moderate binding affinity and selectivity at the μ receptor, with compound 7b showing the highest affinity at this receptor with a Ki value of 40 nM, and 6- and 25-fold selectivity against δ and κ receptors, respectively. Function assays showed that indolopropellanes 7b and 7c possessed full agonistic activity at all the opioid receptors indicating a different interaction model existed.
Syntheses of 4,6′-epoxymorphinan derivatives and their pharmacologies
Nemoto, Toru,Fujii, Hideaki,Narita, Minoru,Miyoshi, Kan,Nakamura, Atsushi,Suzuki, Tsutomu,Nagase, Hiroshi
, p. 4304 - 4312 (2008/12/20)
A modification of the message site in the skeleton of naltrexone was carried out to improve the potency and selectivity of the compound for an opioid receptor subtype. In the course of conversion, we synthesized 7-membered ring ether derivatives, which ha
Formamidinesulfinic acid reduction of dihydrocodeinone derivatives
Brine,Boldt,Coleman,et al.
, p. 1555 - 1557 (2007/10/09)
Treatment of dihydrocodeinone (1f) with formamidinesulfinic acid afforded mixtures of dihydrothebainone (3a) dihydroisothebainol dihydroisothenainol (4a) under both homogeneous and heterogeneous conditions. Similar treatment of 14-hydroxydihydrocodeinone
