German_2011_J.Med.Chem_54_7259

Reference

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

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Citations formats

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