Synthesis of N-phenyl-N-(3-(piperidin-1-yl)propyl)benzofuran-2-carboxamides as new selective ligands for sigma receptors.
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 K(i) values ranging from 7.8 to 34nM. Ligand KSCM-1 with two methoxy substituents at C-5 and C-6 of the benzofuran ring, and K(i)=27.5nM at sigma-1 was found to be more selective for sigma-1 over sigma-2.
Department of Natural Sciences, Savannah State University, College of Sciences and Technology, Savannah, Georgia 31404, USA. marriottk@savannahstate.edu
Karla-Sue C
KS
Marriott
Andrew Z
AZ
Morrison
Misty
M
Moore
Olarongbe
O
Olubajo
Leonard E
LE
Stewart
D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D008024:Ligands; D011869:Radioligand Assay; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000097605:Sigma-1 Receptor
D001572:Benzofurans; D008024:Ligands; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor