Substituted (pyrroloamino)pyridines: potential agents for the treatment of Alzheimer's disease.
A novel series of substituted (pyrroloamino)pyridines was synthesized, and the compounds were evaluated for cholinomimetic-like properties in vitro (inhibition of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine-induced dementia) as potential agents for the treatment of Alzheimer's disease. Compounds displaying significant activity were more broadly evaluated, which revealed the presence of a desirable adrenergic component of activity. The synthesis and structure-activity relationships for this series is presented, along with the biological profiles of selected compounds.
Davis
L
L
Hoechst-Roussel Pharmaceuticals Inc., Somerville, New Jersey 08876, USA.
Olsen
G E
GE
Klein
J T
JT
Kapples
K J
KJ
Huger
F P
FP
Smith
C P
CP
Petko
W W
WW
Cornfeldt
M
M
Effland
R C
RC
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D011813:Quinuclidinyl Benzilate / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D001679:Biogenic Amines; D011725:Pyridines; D011813:Quinuclidinyl Benzilate