Potential anxiolytic agents. 3. Novel A-ring modified pyrido[1,2-a]benzimidazoles.
A variety of pyrido[1,2-a]benzimidazoles (PBIs) modified on the A-ring were prepared and evaluated for affinity to the benzodiazepine binding site on the GABA-A receptor and in animal models predictive of anxiolytic activity in humans. A-ring benzo-fused derivative 7 exhibited potent activity, as did the 6- and 7-pyrido compounds 3 and 4.
Maryanoff
B E
BE
Drug Discovery, R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477, USA.
Nortey
S O
SO
McNally
J J
JJ
Sanfilippo
P J
PJ
McComsey
D F
DF
Dubinsky
B
B
Shank
R P
RP
Reitz
A B
AB
D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D014151:Anti-Anxiety Agents; D001562:Benzimidazoles; D011725:Pyridines