Discovery of biaryl inhibitors of H+/K+ ATPase.

Abstract:

:We report the identification of a novel biaryl template for H(+)/K(+) ATPase inhibition. Evaluation of critical SAR features within the biaryl imidazole framework and the use of pharmacophore modelling against known imidazopyridine and azaindole templates suggested that the geometry of the molecule is key to achieving activity. Herein we present our work optimising the potency of the molecule through modifications and substitutions to each of the ring systems. In particular sub-micromolar potency is achieved with (4b) presumably through a proposed intramolecular hydrogen bond that ensures the required imidazole basic centre is appropriately located.

journal_name

Bioorg Med Chem Lett

authors

Garton N,Bailey N,Bamford M,Demont E,Farre-Gutierrez I,Hutley G,Bravi G,Pickering P

doi

10.1016/j.bmcl.2009.12.040

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

1049-54

issue

3

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)01755-7

journal_volume

20

pub_type

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