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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DA015579-03
Application #
6798718
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2003-02-28
Project End
2005-05-13
Budget Start
2004-09-25
Budget End
2005-05-13
Support Year
3
Fiscal Year
2004
Total Cost
$24,730
Indirect Cost
Name
Clemson University
Department
Chemistry
Type
Schools of Engineering
DUNS #
042629816
City
Clemson
State
SC
Country
United States
Zip Code
29634
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