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.
MeSH terms
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Animals
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Bone Resorption / pathology
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Cell Line
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Culture Techniques
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Humans
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Ligands
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Naphthyridines / chemical synthesis*
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Naphthyridines / chemistry
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Naphthyridines / pharmacology
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Platelet Aggregation / drug effects
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Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
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Propionates / chemical synthesis*
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Propionates / chemistry
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Propionates / pharmacology
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Rats
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Rats, Sprague-Dawley
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Sulfonamides / chemical synthesis*
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
Substances
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2-benzenesulfonylamino-3-(4-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)benzoylamino)propionic acid
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Ligands
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Naphthyridines
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Platelet Glycoprotein GPIIb-IIIa Complex
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Propionates
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Sulfonamides