Isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives as potent alpha(4)beta(1) integrin antagonists |
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| Authors: | Duplantier A J Beckius G E Chambers R J Chupak L S Jenkinson T H Klein A S Kraus K G Kudlacz E M McKechney M W Pettersson M P Whitney C A Milici A J |
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| Affiliation: | Pfizer Global Research and Development, Groton Labs, Eastern Point Road, Groton, CT 06340, USA. allen_j_duplantier@groton.pfizer.com |
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| Abstract: | A series of isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives derived from LDV was found to be a potent antagonist of the alpha(4)beta(1) integrin. The synthesis and SAR leading up to 3-[3-(1-[-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino]-3-methyl-butyl)-isoxazol-5-yl]-propionic acid (22) are reported. In an allergic mouse model, compound 22 was efficacious delivered systemically (58% inhib @ 10 mg/kg, sc) as well as by intra-tracheal instillation (ED(50)=2 microg/kg). |
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