Vincent E. Groppi

Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide as an agonist of the α7 nicotinic acetylcholine receptor: In vitro and in vivo activity

A novel alpha7 nAChR agonist, N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (3a, PHA-709829), has been identified for the potential treatment of cognitive deficits in schizophrenia. The compound shows potent and selective alpha7 in vitro activity, excellent brain penetration, good rat oral bioavailability and robust in vivo efficacy in a rat auditory sensory gating model.

Cyanoguanidine bioisosteres in potassium channel openers: Evaluation of 3,4-disubstituted-1,2,5-thiadiazole-1-oxides

Abstract Bioisosteric substitution of the cyanoguanidine group found in pinacidil ( 1 ) with a 3,4-diamino-1,2,5-thiadiazole-1-oxide moiety and replacement of the 4-aminopyridine group with a 3,5-dichlorophenyl group has resulted in a new structural class of potassium channel opener (PCO).

6-Alkoxyisoindolin-1-one based dopamine D2 partial agonists as potential antipsychotics

A series of 6-alkoxyisoindolin-1-ones with a magic shotgun pharmacological profile are presented as potential antipsychotics. The in vitro pharmacological profile includes D(2) partial agonism (30-55%), 5-HT(1A) partial agonism (60-90%), and 5-HT(2A) antagonism. Selected compounds in this series displayed good in vivo activity and potency.