Part II: Piperazinyl-glutamate-pyridines as potent orally bioavailable P2Y12 antagonists for inhibition of platelet aggregation
| Autor: | John J, Parlow, Mary W, Burney, Brenda L, Case, Thomas J, Girard, Kerri A, Hall, Peter K, Harris, Ronald R, Hiebsch, Rita M, Huff, Rhonda M, Lachance, Deborah A, Mischke, Stephen R, Rapp, Rhonda S, Woerndle, Michael D, Ennis |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Molecular Structure
Platelet Aggregation Pyridines Organic Chemistry Clinical Biochemistry Administration Oral Glutamic Acid Pharmaceutical Science CHO Cells Biochemistry Receptors Purinergic P2Y12 Rats Inhibitory Concentration 50 Structure-Activity Relationship Cricetulus Dogs Fibrinolytic Agents Piperidines Cricetinae Drug Discovery Purinergic P2 Receptor Antagonists Animals Humans Molecular Medicine Molecular Biology |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 20:1388-1394 |
| ISSN: | 0960-894X |
| Popis: | Efforts to refine the SAR of the piperazinyl-glutamate-pyridines for more potent analogs with improved pharmacokinetic profiles are described. Exploring substituted piperidines and other ring systems at the 4-pyridyl position led to compounds with improved potency and pharmacokinetic properties over candidate I. In particular, compounds 4t and 5t were discovered with a 10-fold improvement over potency and improved pharmacokinetic profiles in both the rat and dog. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect