Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for neuronal nicotinic acetylcholine receptors |
| |
Authors: | Murineddu Gabriele Murruzzu Caterina Curzu Maria M Chelucci Giorgio Gotti Cecilia Gaimarri Annalisa Legnani Laura Toma Lucio Pinna Gerard A |
| |
Institution: | Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, via F. Muroni 23/A, 07100 Sassari, Italy. muri@uniss.it |
| |
Abstract: | Alpha series of novel 3,6-diazabicyclo3.1.1]heptane derivatives 4a-f was synthesized and their affinity and selectivity towards alpha4beta2 and alpha7 nAChR subtypes were evaluated. The results of the current study revealed a number of compounds (4a, 4b and 4c) having a very high affinity for alpha4beta2 (K(i) at alpha4beta2 ranging from 0.023 to 0.056 nM) versus alpha7 nAChR subtypes; among these compounds, the 3-(6-bromopyridin-3-yl)-3,6-diazabicyclo3.1.1]heptane 4c was found to be the most alpha7alpha4beta2 selective term in receptor binding assays (alpha7alpha4beta2=1295). Moreover, compound 4d also had high affinity for the alpha4beta2 nAChR subtype (K(i)=1.2 nM) with considerably high selectivity (alpha7/alpha4beta2=23300). |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|