Aminothiazolomorphinans with Mixed kappa and mu Opioid Activity

作者：Zhang Tangzhi; Yan Zhaohua; Sromek Anna; Knapp Brian I; Scrimale Thomas; Bidlack Jean M; Neumeyer John L^*

来源：Journal of Medicinal Chemistry, 2011, 54(6): 1903-1913.

DOI：10.1021/jm101542c

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-cydopropylmorphina:a (3), 3-aminothiazole derivatives of cyclorphan (1) containing a primary amino group displayed high affinity and selectivity at the kappa and mu opioid receptors. [(35)S]GTP gamma S binding assays showed that the aminothiazolomorphinans were kappa agonists with mixed agonist and antagonist activity at the mu opioid receptor. These novel N'-monosubstituted aminothiazole-derived morphinans may be valuable for the development of drug abuse medications.

• 出版日期2011-3-24