Synthesis of N-phenyl-N-(3-(piperidin-1-yl)propyl)benzofuran-2-carboxamides as new selective ligands for sigma receptors

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Authors
Marriott, Karla-Sue C.
Morrisson, Andrew Z.
Moore, Misty
Olubajo, Olarongbe
Stewart, Leonard E.
Advisors
Department
Savannah State University
Keywords
sigma receptors
ligand
benzofuran
carboxamide
organic chemistry
Issue Date
2012-12
Type
Article
Language
en
Description
Other Titles
Abstract
Novel benzofuran-2-carboxamide ligands, which are selective for sigma receptors, have been synthesized via a microwave-assisted Perkin rearrangement reaction and a modified Finkelstein halogen-exchange used to facilitate N-alkylation. The ligands synthesized are the 3-methyl-N-phenyl-N-(3-(piperidin-1-yl)propyl)benzofuran-2-carboxamides (KSCM-1, KSCM-5 and KSCM-11). The benzofuran-2-carboxamide structure was N-arylated and N-alkylated to include both N-phenyl and N-(3-(piperidin-1-yl)propyl substituents, respectively. These new carboxamides exhibit high affinity at the sigma-1 receptor with Ki values ranging from 7.8 to 34 nM. Ligand KSCM-1 with two methoxy substituents at C-5 and C-6 of the benzofuran ring, and Ki = 27.5 nM at sigma-1 was found to be more selective for sigma-1 over sigma-2.