8-Fluoroimidazo[1,2-a]pyridine: synthesis, physicochemical properties and evaluation as a bioisosteric replacement for imidazo[1,2-a]pyrimidine in an allosteric modulator ligand of the GABA A receptor.
8-Fluoroimidazo[1,2-a]pyridine has been established as a physicochemical mimic of imidazo[1,2-a]pyrimidine, using both in silico and traditional techniques. Furthermore, a novel synthesis of a 3,7-disubstituted-8-fluoroimidazopyridine 3 has been developed and the utility of the physicochemical mimicry has been demonstrated in an in vitro system. Here, the 8-fluoroimidazopyridine ring contained in ligand 3 acts as a bioisosteric replacement for imidazopyrimidine in the GABA(A) receptor modulator 2.
Humphries
Alexander C
AC
The Neuroscience Research Centre, Merck Sharp and Dohme, Terlings Park, Harlow, Essex CM20 2QR, UK. alexander_humphries@merck.com
Gancia
Emanuela
E
Gilligan
Myra T
MT
Goodacre
Simon
S
Hallett
David
D
Merchant
Kevin J
KJ
Thomas
Steve R
SR
D000494:Allosteric Regulation / Q000187:drug effects*; D000818:Animals; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018755:GABA Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000819:agonists; D013329:Structure-Activity Relationship
C509381:8-fluoroimidazo(1,2-a)pyridine; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D007093:Imidazoles; D008024:Ligands; D011725:Pyridines; D011994:Recombinant Proteins