Spirocyclic nonpeptide glycoprotein IIb-IIIa antagonists. Part 1: design of potent and specific 3,9-diazaspiro[5.5]undecanes

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

doi:10.1016/s0960-894x(01)00215-3

Spirocyclic nonpeptide glycoprotein IIb-IIIa antagonists. Part 1: design of potent and specific 3,9-diazaspiro[5.5]undecanes

Bioorg Med Chem Lett. 2001 May 21;11(10):1289-92. doi: 10.1016/s0960-894x(01)00215-3.

Authors

M S Smyth¹, J Rose, M M Mehrotra, J Heath, G Ruhter, T Schotten, J Seroogy, D Volkots, A Pandey, R M Scarborough

Affiliation

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

PMID: 11392539
DOI: 10.1016/s0960-894x(01)00215-3

Abstract

The synthesis and biological activity of novel glycoprotein IIb-IIla antagonists containing the 3,9-diazaspiro[5.5]undecane nucleus are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility of the spirocyclic structures as a 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