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
Me. Duggan et al., 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, J MED CHEM, 43(20), 2000, pp. 3736-3745
Modification of the potent fibrinogen receptor (alpha(IIb)beta(3)) antagoni
st 1 generated compounds with high affinity for the vitronectin receptor al
pha(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.