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
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