Spirocyclic nonpeptide glycoprotein IIb-IIIa antagonists. Part 2: design of potent antagonists containing the 3-azaspiro[5.5]undecanes

A Pandey; J Seroogy; D Volkots; M S Smyth; J Rose; M M Mehrotra; J Heath; G Ruhter; T Schotten; R M Scarborough

doi:10.1016/s0960-894x(01)00216-5

Spirocyclic nonpeptide glycoprotein IIb-IIIa antagonists. Part 2: design of potent antagonists containing the 3-azaspiro[5.5]undecanes

Bioorg Med Chem Lett. 2001 May 21;11(10):1293-6. doi: 10.1016/s0960-894x(01)00216-5.

Authors

A Pandey¹, J Seroogy, D Volkots, M S Smyth, J Rose, M M Mehrotra, J Heath, G Ruhter, T Schotten, R M Scarborough

Affiliation

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

PMID: 11392540
DOI: 10.1016/s0960-894x(01)00216-5

Abstract

The synthesis and biological activity of novel glycoprotein IIb-IlIa anatagonists containing 3-azaspiro[5.5]undec-9-yl nucleus are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility of the monoazaspirocyclic structure 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
Receptors, Vitronectin / antagonists & inhibitors
Spiro Compounds / chemical synthesis*
Spiro Compounds / pharmacokinetics
Spiro Compounds / pharmacology
Structure-Activity Relationship

Substances

Aza Compounds
Platelet Aggregation Inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex
Receptors, Vitronectin
Spiro Compounds