Author/Authors :
Richard L. Elliott، نويسنده , , Keith B. Ryther، نويسنده , , David J. Anderson، نويسنده , , Marietta Piattoni-Kaplan، نويسنده , , Theresa A. Kuntzweiler، نويسنده , , Diana Donnelly-Roberts، نويسنده , , Stephen P. Arneric، نويسنده , , Mark W. Holladay، نويسنده ,
Abstract :
A novel series of 2-(2′-furo[3,2-b]pyridinyl) pyrrolidines has been synthesized and evaluated as novel nicotinic acetylcholine receptor ligands. Changing the pyrrolidine stereochemistry and N-substitution pattern afforded analogs with Ki values ranging from 2.7 to 97 nM. Rubidium efflux studies revealed that these compounds had intrinsic activities ranging from 9–58% that of nicotine in the IMR-32 cell line and 6–81% in the K177 cell line. The N(Me)-2(S) analog 3a demonstrated good selectivity in the K177 cell line (α4β2 receptor) versus the IMR-32 cells (α3βx receptor) and TE 671 cells (α1 neuromuscular receptor), and was a partial agonist with an EC50 value of 141 nM in dopamine release assay using rat striatal slices.
