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

Mukund M Mehrotra; Julie A Heath; Jack W Rose; Mark S Smyth; Joseph Seroogy; Deborah L Volkots; Gerd Ruhter; Theo Schotten; Lisa Alaimo; Gary Park; Anjali Pandey; Robert M Scarborough

doi:10.1016/s0960-894x(02)00095-1

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

Bioorg Med Chem Lett. 2002 Apr 8;12(7):1103-7. doi: 10.1016/s0960-894x(02)00095-1.

Authors

Mukund M Mehrotra¹, Julie A Heath, Jack W Rose, Mark S Smyth, Joseph Seroogy, Deborah L Volkots, Gerd Ruhter, Theo Schotten, Lisa Alaimo, Gary Park, Anjali Pandey, Robert M Scarborough

Affiliation

¹ COR Therapeutics, Inc., Department of Medicinal Chemistry, South San Francisco, CA 94080, USA.

PMID: 11909727
DOI: 10.1016/s0960-894x(02)00095-1

Abstract

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.

MeSH terms

Administration, Oral
Animals
Aza Compounds / chemical synthesis
Aza Compounds / pharmacokinetics
Aza Compounds / pharmacology
Biological Availability
Blood Platelets / drug effects
Humans
Inhibitory Concentration 50
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

Substances

Aza Compounds
Platelet Aggregation Inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex
Spiro Compounds