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

Methods The chemistry involved the design and synthesis of two sets of oxazolomorphinans having the new heteroring anellated to the A-ring of the morphinan backbone. Binding affinities of the newly synthesized compounds at opioid receptors were determined by in vitro competition binding assays using rat brain (μ, δ) and guinea pig brain ( ) membranes and employing [H]DAMGO (μ), [H] [Ile]deltorphin II (δ) and [H]U-69,593 ( ) as specific opioid radioligands. The in vitro pharmacological activities were established using [S]GTPgS functional assays in membranes from Chinese hamster ovary (CHO) cells expressing human opioid receptors.