Syntheses and structure-activity relationship (SAR) studies of 2,5-diazabicyclo[2.2.1]heptanes as novel alpha7 neuronal nicotinic receptor (NNR) ligands

Tao Li; William H Bunnelle; Keith B Ryther; David J Anderson; John Malysz; Rosalind Helfrich; Jens H Grønlien; Monika Håkerud; Dan Peters; Michael R Schrimpf; Murali Gopalakrishnan; Jianguo Ji

doi:10.1016/j.bmcl.2010.04.105

Syntheses and structure-activity relationship (SAR) studies of 2,5-diazabicyclo[2.2.1]heptanes as novel alpha7 neuronal nicotinic receptor (NNR) ligands

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3636-9. doi: 10.1016/j.bmcl.2010.04.105. Epub 2010 Apr 28.

Authors

Tao Li¹, William H Bunnelle, Keith B Ryther, David J Anderson, John Malysz, Rosalind Helfrich, Jens H Grønlien, Monika Håkerud, Dan Peters, Michael R Schrimpf, Murali Gopalakrishnan, Jianguo Ji

Affiliation

¹ Neuroscience Research, GPRD, Abbott, Abbott Park, IL 60064-6117, USA. Tao.Li@abbott.com

PMID: 20472430
DOI: 10.1016/j.bmcl.2010.04.105

Abstract

Biaryl substituted 2,5-diazabicyclo[2.2.1]heptanes have been synthesized and tested for their affinity toward alpha7 neuronal nicotinic receptors (NNRs). SAR studies established that 5-N-methyl substituent, heteroaryl linker and the nature of terminal aryl group are critical for the ligand to achieve potent alpha7 NNR agonist activity.

MeSH terms

Animals
Heptanes / chemical synthesis
Heptanes / chemistry*
Heptanes / pharmacology*
Humans
Ligands
Neurons / metabolism
Nicotinic Agonists / chemical synthesis
Nicotinic Agonists / chemistry*
Protein Binding
Radioligand Assay
Rats
Receptors, Nicotinic / drug effects
Receptors, Nicotinic / metabolism
Structure-Activity Relationship

Substances

Heptanes
Ligands
Nicotinic Agonists
Receptors, Nicotinic