Spirocyclic nonpeptide glycoprotein IIb-IIIa antagonists. Part 3: synthesis and SAR of potent and specific 2,8-diazaspiro[4.5]decanes.
The synthesis and biological activity of analogues containing spiro piperidinylpyridine and pyrrolidinylpyridine templates are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility of the spiro structures as central template for nonpeptide RGD mimics.
Mehrotra
Mukund M
MM
COR Therapeutics, Inc., Department of Medicinal Chemistry, South San Francisco, CA 94080, USA.
Heath
Julie A
JA
Rose
Jack W
JW
Smyth
Mark S
MS
Seroogy
Joseph
J
Volkots
Deborah L
DL
Ruhter
Gerd
G
Schotten
Theo
T
Alaimo
Lisa
L
Park
Gary
G
Pandey
Anjali
A
Scarborough
Robert M
RM
D000284:Administration, Oral; D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D001792:Blood Platelets / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001372:Aza Compounds; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013141:Spiro Compounds