Since the elucidation of the structure of the active component of marijuana in 1964 by Gaoni and Mechoulam, several classes of cannabinoids have been developed and evaluated for pharmacophoric effects. Working from the observation that certain aminoalkylindoles exhibit cannabinoid receptor affinity, several series of indoles and pyrroles have been designed and tested. The indoles vvere found to exhibit better receptor affinity than the corresponding pyrroles, supporting the hypothesis that aromatic stacking may play an important role in enhancing the activity of compounds of this type. One study indicated that the pyrroles exhibit higher affinity when they possess an aryl group at the 2-position. Based on this data, it is the focus of this proposal to synthesize multiple series of pyrrole-based compounds containing these aryl groups to test the effects of substituents on the aryl ring and also by functionalizing the naphthoyl group. This synthesis will be carried out through the use of 2-bromopyrrole as a synthon for Suzuki coupling, then a regioselective Friedel-Crafts acylation to append the naphthoyl group.
| Huffman, John W; Padgett, Lea W; Isherwood, Matthew L et al. (2006) 1-Alkyl-2-aryl-4-(1-naphthoyl)pyrroles: new high affinity ligands for the cannabinoid CB1 and CB2 receptors. Bioorg Med Chem Lett 16:5432-5 |
| Padgett, Lea W (2005) Recent developments in cannabinoid ligands. Life Sci 77:1767-98 |
| Huffman, J W; Padgett, L W (2005) Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 12:1395-411 |
