Spirocyclic nonpeptide glycoprotein IIb-IIIa antagonists. Part 3: Synthesis and SAR of potent and specific 2,8-diazaspiro[4.5]decanes

• Published in: Bioorganic & medicinal chemistry letters Vol. 12; no. 7; pp. 1103 - 1107
• Main Authors: MEHROTRA, Mukund M, HEATH, Julie A, PANDEY, Anjali, SCARBOROUGH, Robert M, ROSE, Jack W, SMYTH, Mark S, SEROOGY, Joseph, VOLKOTS, Deborah L, RUHTER, Gerd, SCHOTTEN, Theo, ALAIMO, Lisa, PARK, Gary
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 08-04-2002
• Subjects: Administration, Oral; Animals; Aza Compounds - chemical synthesis; Aza Compounds - pharmacokinetics; Aza Compounds - pharmacology; Biological and medical sciences; Biological Availability; Blood Platelets - drug effects; Blood. Blood coagulation. Reticuloendothelial system; Humans; Inhibitory Concentration 50; Medical sciences; Pharmacology. Drug treatments; Platelet Aggregation Inhibitors - chemical synthesis; Platelet Aggregation Inhibitors - pharmacokinetics; Platelet Aggregation Inhibitors - pharmacology; Platelet Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors; Rats; Rats, Sprague-Dawley; Spiro Compounds - chemical synthesis; Spiro Compounds - pharmacokinetics; Spiro Compounds - pharmacology; Structure-Activity Relationship; Glycoprotein IIbIIIa; Intravenous administration; Rat; Nitrogen heterocycle; Rodentia; Oral administration; Non peptide compound; Anticoagulant; Bioavailability; In vitro; Antiplatelet agent; Spiran; In vivo; Vertebrata; Mammalia; Pyridine; Structure activity relation; Carboxylic acid; Animal; Carboxamide; Ureas; Antagonist; Pharmacokinetics; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00095-1

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.