Key result
Novel isoxazolecarboxamide analogue XU065 demonstrates potent oral antiplatelet effects in preclinical canine models.
Why the study?
Previously reported benzamide glycoprotein IIb/IIIa antagonists showed excellent in vitro potency but poor in vivo inhibition of platelet aggregation.
XU065 shows oral antiplatelet efficacy in dogs; extends benzamide modifications but leaves open human translation.
Despite the excellent in vitro potency of a series of benzamide glycoprotein IIb/IIIa antagonists, which have been reported previously, poor in vivo potency in the inhibition of platelet aggregation was observed when the most potent inhibitor XU057 was dosed intravenously to dogs. In this communication, we report that replacement of the benzamide in XU057 with an isoxazolecarboxamide resulted in significant improvement in in vivo potency. More importantly, the analogue XU065 showed an excellent oral antiplatelet effect in dogs.
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Xue et al. (1998) studied this question. XU065 (isoxazole analogue) was evaluated. The isoxazolecarboxamide analogue XU065 demonstrated excellent oral antiplatelet effects in dogs, and multiple pyrazole and isoxazole derivatives were efficiently synthesized.
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