Structural highlights
Publication Abstract from PubMed
The association of two pharmacophoric entities generates so-called 'twin drugs' or dimer derivatives. We applied this approach for the design of a small compound library for the interaction with alpha4beta2( *) nicotinic acetylcholine receptors (nAChRs). In this compound series, the nAChR ligand N,N-dimethyl-2-(pyridin-3-yloxy)ethan-1-amine 9 served as one pharmacological entity and it was initially kept constant as one part of the 'twin' compound. 'Twin' compounds with identical or non-identical entities using the 'no linker mode' or 'overlap' mode were synthesized and evaluated for their nAChR affinities. Compound 17a showed the highest affinity for the alpha4beta2( *) nAChR subtype (Ki=0.188 nM) and its (di)fluoro analogs could retain nanomolar affinities, when replacing pyridine as the hydrogen bond acceptor system by mono- or difluoro-phenyls. The 'twin drug' approach proved to provide compounds with high affinity and subtype selectivity for alpha4beta2( *) nAChRs.
The twin drug approach for novel nicotinic acetylcholine receptor ligands.,Tomassoli I, Gundisch D Bioorg Med Chem. 2015 Aug 1;23(15):4375-89. doi: 10.1016/j.bmc.2015.06.034. Epub , 2015 Jun 20. PMID:26142318[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tomassoli I, Gundisch D. The twin drug approach for novel nicotinic acetylcholine receptor ligands. Bioorg Med Chem. 2015 Aug 1;23(15):4375-89. doi: 10.1016/j.bmc.2015.06.034. Epub , 2015 Jun 20. PMID:26142318 doi:http://dx.doi.org/10.1016/j.bmc.2015.06.034
