Aza-bicyclic amino acid carboxamides as α4β1/α4β7 integrin receptor antagonists
| Autor: | Pamela J. Hornby, Bruce P. Damiano, Alexey B. Dyatkin, N. H. Wallace, M. Carolyn Fisher, Stephen M. Prouty, Bruce E. Maryanoff, Edward S. Kimball, Wei He, Rosemary J. Santulli, Craig R. Schneider, Yong Gong, William A. Kinney, Craig J. Diamond, Tamara A. Miskowski |
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| Rok vydání: | 2005 |
| Předmět: |
chemistry.chemical_classification
Bicyclic molecule medicine.drug_class Stereochemistry Organic Chemistry Clinical Biochemistry Substituent Pharmaceutical Science Carboxamide Biological activity Biochemistry Chemical synthesis In vitro Amino acid chemistry.chemical_compound chemistry In vivo Drug Discovery medicine Molecular Medicine Molecular Biology |
| Zdroj: | Bioorganic & Medicinal Chemistry. 13:6693-6702 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2005.07.022 |
| Popis: | A series of N-carboxy, N-alkyl, and N-carboxamido azabicyclo[2.2.2]octane carboxamides were prepared and assayed for inhibition of α4β1-VCAM-1 and α4β7-MAdCAM-1 interactions. Potency and α4β1/α4β7 selectivity were sensitive to the substituent R1–R3 in the structures 6, 7, and 8. Several compounds demonstrated low nanomolar balanced α4β1/α4β7 in vitro activity. Two compounds were selected for in vivo leukocytosis studies and demonstrated increases in circulating lymphocytes up to 250% over control. |
| Databáze: | OpenAIRE |
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