Development of novel N-methyl and N-allyl-substituted oxazolomorphinans and their interaction with opioid receptors

MEETING ABSTRACT Open Access De elopmen o no el N-me hyl and N-allyl- subs i u ed oxazolomo phinans and hei in e ac ion wi h opioid ecep o s A ila Sipos 1,2* , Le en e Gi án 1 , Sándo Be ényi 1 , Sándo An us 1 , Helmu Schmidhamme 2 , Ma iana Spe ea 2 F om 17 h Scien i ic Symposium o he Aus ian Pha macological Socie y (APHAR). Join mee ing wi h he Hunga ian Socie y o Expe imen al and Clinical Pha macology (MFT) Innsb uck, Aus ia. 29-30 Sep embe 2011 Backg ound The need o opioid analgesics wi h educed undesi able side-e ec s has ini ia ed a as amoun o scien i ic e o s, which ha e led o a numbe o new opioid ligands and sig- ni ican expansion o knowledge in opioid pha macology. The de elopmen o mo phinans anella ed wi h he e o- cycles ga e ise o se e al po en ial he apeu ic agen s and use ul pha macological ools. Me hods The chemis y in ol ed he design and syn hesis o wo se s o oxazolomo phinans ha ing he new he e o ing anella ed o he A- ing o he mo phinan backbone. Binding a ini ies o he newly syn hesized compounds a opioid ecep o s we e de e mined by in i o compe i ion binding assays using a b ain (μ,δ)andguineapigb ain () memb anes and employing [ 3 H]DAMGO (μ), [ 3 H] [Ile 5,6 ]del o phin II (δ)and[ 3 H]U-69,593 () as speci ic opioid adioligands. The in i o pha macological ac i - i ies we e es ablished using [ 35 S]GTPgS unc ional assays in memb anes om Chinese hams e o a y (CHO) cells exp essing human opioid ecep o s. Resul s Binding s udies on he newly syn hesized N-me hyl and N-allyl de i a i es o opioid ecep o s e ealed ema kable esul s o h ee compounds: he amino- subs i u ed N-me hyloxazolomo phinan showed high a ini y and selec i i y o he μopioid ecep o , while wo N-allyloxazolomo phinans we e ound o in e ac wi h high a ini y wi h μand si es and mode a e binding owa ds δ ecep o s. In ligand-s imula ed [ 35 S] GTPgS binding s udies, he N-me hyl congene ac ed as a po en and ull agonis a he μ ecep o . The wo N-allyl de i a i es showed an agonis ic e ec s a μand  ecep o s. Conclusions The design and syn hesis o no el oxazolomo phinans led o an in e es ing al e a ion in opioid ac i i y by in luencing he biological and pha macological p o ile o hese compounds in e ac ing wi h μ,δand opioid ecep o s. Acknowledgemen s Suppo ed by he Hunga ian Resea ch Fund (K81701) and he Aus ian Science Fund (FWF: P15481 and TRP 19-B18). Au ho de ails 1 Depa men o O ganic Chemis y, Uni e si y o Deb ecen, 4010 Deb ecen, Hunga y. 2 Depa men o Pha maceu ical Chemis y, Ins i u e o Pha macy, and Cen e o Molecula Biosciences, Uni e si y o Innsb uck, 6020 Innsb uck, Aus ia. Published: 5 Sep embe 2011 doi:10.1186/1471-2210-11-S2-A13 Ci e his a icle as: Sipos e al.: De elopmen o no el N-me hyl and N-allyl-subs i u ed oxazolomo phinans and hei in e ac ion wi h opioid ecep o s. BMC Pha macology 2011 11(Suppl 2):A13. * Co espondence: [email p o ec ed].a 1 Depa men o O ganic Chemis y, Uni e si y o Deb ecen, 4010 Deb ecen, Hunga y Full lis o au ho in o ma ion is a ailable a he end o he a icle Sipos e al.BMC Pha macology 2011, 11(Suppl 2):A13 h p://www.biomedcen al.com/1471-2210/11/S2/A13 © 2011 Sipos e al; licensee BioMed Cen al L d. This is an open access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion License (h p://c ea i ecommons.o g/licenses/by/2.0), which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed.