155778-25-9Relevant academic research and scientific papers
3-Amidoquinuclidine derivatives: Synthesis of compounds and inhibition of butyrylcholinesterase
Odzak, Renata,Tomic, Srdanka
, p. 90 - 98 (2008/02/05)
The synthesis of racemic and enantiomerically pure 3- butanamidoquinuclidines ((±)-Bu, (R)-Bu and (S)-Bu), (1-3) and 3-benzamidoquinuclidines ((±)-Bz, (R)-Bz, and (S)-Bz), (4-6) is described. The N-quaternary derivatives, N-benzyl-3-butanamidoquinuclidinium bromides ((±)-BnlBu, (R)-BnlBu and (S)-BnlBu), (7-9) and N-benzyl-3-benzamidoquinuclidinium bromides ((±)-BnlBz, (R)-BnlBz and (S)-BnlBz), (10-12) were subsequently synthesized. The interaction of the four enantiomerically pure quaternary derivatives with horse serum butyrylcholinesterase (BChE) was tested. All tested compounds inhibited the enzyme. The best inhibitior of the enzyme was (S)-BnlBz with a Ki = 3.7 μM. The inhibitor potency decreases in order (S)-BnlBz > (R)-BnlBz ? (R)-BnlBu > (S)-BnlBu.
Discovery and structure-activity relationship of quinuclidine benzamides as agonists of α7 nicotinic acetylcholine receptors
Bodnar, Alice L.,Cortes-Burgos, Luz A.,Cook, Karen K.,Dinh, Dac M.,Groppi, Vincent E.,Hajos, Mihaly,Higdon, Nicole R.,Hoffmann, William E.,Hurst, Raymond S.,Myers, Jason K.,Rogers, Bruce N.,Wall, Theron M.,Wolfe, Mark L.,Wong, Erik
, p. 905 - 908 (2007/10/03)
A library of benzamides was tested for α7 nicotinic acetylcholine receptor (nAChR) agonist activity using a chimeric receptor in a functional, cell-based, high-throughput assay. From this library, quinuclidine benzamides were found to have α7 nAChR agonist activity. The SAR diverged from the activity of this compound class verses the 5-HT3 receptor, a structural homologue of the α7 nAChR. PNU-282987, the most potent compound from this series, was also shown to open native α7 nAChRs in cultured rat neurons and to reverse an amphetamine-induced gating deficit in rats.
