Bioisosteric replacement in the design and synthesis of ligands for nicotinic acetylcholine receptors

Article abstract of DOI:10.1007/s00044-005-0137-8

A series of ethers containing pyrrolidine and/or pyridine bioisosteres was synthesized and evaluated as nicotinic ligands. The dimethylaminoethoxypyridines 6 and 7 inhibited the specific binding of (-)-[³H]Nicotine with Ki values of 300 nM and 450 nM, respectively. Compounds 8 and 9 were found to have Ki values of 3390 nM and 360 nM. These results suggest that dialkylamino and appropriately substituted benzene rings (NO₂, 8; OH, 9) are bioisosteric replacements for pyrrolidine and pyridine, respectively. Birkhaeuser Boston 2006.

Full text of DOI:10.1007/s00044-005-0137-8

Med Chem Res 14:5 (2005) 241–259
௠ Birkha¨user Boston 2006
DOI: 10.1007/s00044-005-0137-8

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

257

258

Received:
06-20-05
Accepted:
09-21-05
259