188341-29-9Relevant academic research and scientific papers
Derivatives of flavonepenthone: Kappa opioid receptor selectivity in an N-methylmorphinan
Bermejo, Fernando Martinez,Husbands, Stephen M.,Lewis, John W.
, p. 1721 - 1727 (2007/10/03)
To extend our investigation of analogs of the orvinols incorporating phenyl groups constrained in appropriately located fixed conformations, a series of analogs of flavonepenthone have been prepared and evaluated in opioid binding assays. Acid-catalyzed rearrangement of phenyldihydrothevinone gave a 7:1 mixture of (E)- and (Z)-isomers; the corresponding orvinol gave a corresponding 9:1 mixture. The 3,4-substitution pattern in the major isomer was manipulated to give a series of analogs for evaluation. Surprisingly, the flavonepenthone analogs showed selectivity for κ opioid receptors, and the (E)-4-hydroxy-3-methoxy isomer with K(i)(κ) = 0.14 nM and selectivity κ/δ = 40 and κ/μ = 32 is, to our knowledge, the most selective N- methylmorphinan derivative so far reported. It will be the subject of a full pharmacological evaluation.
New nepenthone and thevinone derivatives
Marton, Janos,Simon, Csaba,Hosztafi, Sandor,Szabo, Zoltan,Marki, Arpad,Borsodi, Anna,Makleit, Sandor
, p. 369 - 382 (2007/10/03)
The diastereoselective reaction of thevinone (2a) and nepenthone (2c) and their dihydro derivatives (2b and d) with Grignard reagents afforded new N-substituted (20S)- and (20R)-phenyI-6,14-ethenomorphinan derivatives (6a-y). The Grignard reaction of the N-substituted-N-demethyl derivatives 4a-f and 4m-r with methylmagnesium iodide resulted in the (20R)-phenyl tertiary alcohols 5a-f and 5m-r, respectively, but the conversion of 4g-l and that of the N-substituted-dihydrothevinone derivatives with phenylmagnesium bromide afforded the (20S)-phenyl derivatives 5g-l and 5s-y, respectively. The N-cyclopropylmethyl-, N-β-phenylethyl-, and N-propyl derivatives were prepared by the 3-O-demethylation of compounds 5. For the synthesis of the N-allyl-, N-dimethylallyl-, and N-propargyl compounds 2a-d were reacted with the corresponding Grignard reagent, and treatment of the products with cyanogen bromide gave the cyanamides 8a-d. These latter compounds were transformed into 10a,b,d, whose alkylation led to the target derivatives 6d-f, j-l, p-r, and w-y. The biochemical investigation of these substances showed that the affinities to the δ-opioid receptors were high, but the selectivity was low. Tn two cases (6c and 11d) a μ-opioid receptor specificity was observed.
