Work

Aminothiazolomorphinans with Mixed κ and μ Opioid Activity

Year: 2011

Type: article

Abstract: A series of N-substituted and N'-substituted aminothiazole-derived morphinans (5) were synthesized for expanding the structure-activity relationships of aminothiazolo-morphinans. Although their affinities were somewhat lower than their prototype aminothiazolo-N-cyclopropylmorphinan (3), 3-aminothiazole derivatives of cyclorphan (1) containing a primary amino group displayed high affinity and selectivity at the κ and μ opioid receptors. [(35)S]GTPγS binding assays showed that the aminothiazolomorphinans were κ agonists with mixed agonist and antagonist activity at the μ opioid receptor. These novel N'-monosubstituted aminothiazole-derived morphinans may be valuable for the development of drug abuse medications.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/jm101542c