Isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives as potent α4β1 integrin antagonists

doi:10.1016/S0960-894X(01)00511-X

Bioorganic & Medicinal Chemistry Letters

Volume 11, Issue 19, 8 October 2001, Pages 2593-2596

https://doi.org/10.1016/S0960-894X(01)00511-X Get rights and content

Abstract

A series of isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives derived from LDV was found to be a potent antagonist of the α₄β₁ integrin. The synthesis and SAR leading up to 3-[3-(1-{2-[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 (ED₅₀=2 μg/kg).

The SAR of heterocyclic analogues of LDV is reported.

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Isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives as potent α4β1 integrin antagonists

Abstract

Cell

J. Neuroimmunol.

J. Biol. Chem.

Annu. Rev. Immunol.

J. Cell Biol.

J. Clin. Invest.

J. Clin. Invest.

Neurology

Am. J. Respir. Crit. Care Med.

Isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives as potent α₄β₁ integrin antagonists