Alcohol & Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, Massachusetts 02478, United States.
J Med Chem. 2011 Mar 24;54(6):1903-13. doi: 10.1021/jm101542c. Epub 2011 Feb 25.
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.
为了拓展氨基噻唑吗啡烷类化合物的结构-活性关系,我们合成了一系列 N-取代和 N'-取代的氨基噻唑衍生吗啡烷类化合物(5)。尽管它们的亲和力略低于原型氨基噻唑-N-环丙基吗啡烷(3),但含有伯氨基的环丙基吗啡烷(1)的 3-氨基噻唑衍生物对 κ 和 μ 阿片受体具有高亲和力和选择性。[(35)S]GTPγS 结合测定表明,氨基噻唑吗啡烷类化合物是 κ 阿片受体激动剂,对 μ 阿片受体具有激动剂和拮抗剂混合活性。这些新型的 N'-单取代氨基噻唑衍生吗啡烷类化合物可能对开发药物滥用药物具有重要价值。