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Nonpeptide alpha(v)beta(3) antagonists. 1. Transformation of a potent, integrin-selective alpha(IIb)beta(3) antagonist into a potent alpha(v)beta(3) antagonist.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2000 Oct 05; Vol. 43 (20), pp. 3736-45. - Publication Year :
- 2000
-
Abstract
- Modification of the potent fibrinogen receptor (alpha(IIb)beta(3)) antagonist 1 generated compounds with high affinity for the vitronectin receptor alpha(v)beta(3). Sequential modification of the basic N-terminus of 1 led to the identification of the 5,6,7, 8-tetrahydro[1,8]naphthyridine moiety (THN) as a lipophilic, moderately basic N-terminus that provides molecules with excellent potency and selectivity for the integrin receptor alpha(v)beta(3). The THN-containing analogue 5 is a potent inhibitor of bone resorption in vitro and in vivo. In addition, the identification of a novel, nonpeptide radioligand with high affinity to alpha(v)beta(3) is also reported.
- Subjects :
- Animals
Bone Resorption pathology
Cell Line
Culture Techniques
Humans
Ligands
Naphthyridines chemistry
Naphthyridines pharmacology
Platelet Aggregation drug effects
Propionates chemistry
Propionates pharmacology
Rats
Rats, Sprague-Dawley
Sulfonamides chemistry
Sulfonamides pharmacology
Naphthyridines chemical synthesis
Platelet Glycoprotein GPIIb-IIIa Complex antagonists & inhibitors
Propionates chemical synthesis
Sulfonamides chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 43
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11020288
- Full Text :
- https://doi.org/10.1021/jm000133v