Dr J.W. Lewis's Research Interests

Our research programmes are in the medicinal chemistry and pharmacology of ligands for opioid receptors. We collaborate with Dr James Woods of the University of Michigan, Ann Arbor, Department of Pharmacology.

Buprenorphine (see below) is an opioid analgesic which is currently being developed as a treatment for drug abuse by the US. government. One of our interests is the design and synthesis of analogues of buprenorphine as improved drug abuse treatments.

The investigation of the function of receptor subtypes requires the availability of specific antagonists for the subtypes and, in particular, irreversible antagonists which can immobilise a receptor system by covalent binding. The approach is based on our discovery of a series of irreversible antagonists selective for µ-receptors in which cinnamoylamido groups provide the opportunity for covalent binding. Our current programme seeks systematically-active antagonists for kappa-receptors and delta-receptors.

References

1. S.D. Comer, T.F. Burke, J.W. Lewis and J.H. Woods, "Clocinnamox: a novel systematically-active irreversible opioid antagonist", J. Pharmacol. Exp. Ther., 1992, 262, 1051-1056
2. J.W. Barton, A. Coop and J.W. Lewis, "Diels-Alder reactions of thebaines with cycloalkenones; lithium tetrafluoroborate as a novel Diels-Alder catalyst", Tetrahedron Lett., 1993, 34, 6777-6778
3. A. Coop, K. Grivas, S. Husbands, J.W. Lewis and J. Porter, "Ring constrained analogues of the thevinones; Diels-Alder reactions of thebaines with 1-indenone and methylene cycloalkanones", Tetrahedron Lett., 1995, 36, 1689-1692
4. A. Coop, K. Grivas, S. Husbands and J.W. Lewis, "Methylation of the enolates of thevinone and some analogues", Tetrahedron, 1995, 51, 9681-9698