Title : Deconstruction of the alpha4beta2 nicotinic acetylcholine receptor positive allosteric modulator desformylflustrabromine - German_2011_J.Med.Chem_54_7259 |
Author(s) : German N , Kim JS , Jain A , Dukat M , Pandya A , Ma Y , Weltzin M , Schulte MK , Glennon RA |
Ref : Journal of Medicinal Chemistry , 54 :7259 , 2011 |
Abstract :
Desformylflustrabromine (dFBr; 1), perhaps the first selective positive allosteric modulator of alpha4beta2 neuronal nicotinic acetylcholine (nACh) receptors, was deconstructed to determine which structural features contribute to its actions on receptors expressed in Xenopus ooycytes using two-electrode voltage clamp techniques. Although the intact structure of 1 was found to be optimal, several deconstructed analogs retained activity. Neither the 6-bromo substituent nor the entire 2-position chain is required for activity. In particular, reduction of the olefinic side chain of 1, as seen with 6, not only resulted in retention of activity/potency but in enhanced selectivity for alpha4beta2 versus alpha7 nACh receptors. Pharmacophoric features for the allosteric modulation of alpha4beta2 nACh receptors by 1 were identified. |
PubMedSearch : German_2011_J.Med.Chem_54_7259 |
PubMedID: 21905680 |
German N, Kim JS, Jain A, Dukat M, Pandya A, Ma Y, Weltzin M, Schulte MK, Glennon RA (2011)
Deconstruction of the alpha4beta2 nicotinic acetylcholine receptor positive allosteric modulator desformylflustrabromine
Journal of Medicinal Chemistry
54 :7259
German N, Kim JS, Jain A, Dukat M, Pandya A, Ma Y, Weltzin M, Schulte MK, Glennon RA (2011)
Journal of Medicinal Chemistry
54 :7259