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Synthesis and biological evaluation of optically active Ki16425

2012; Elsevier BV; Volume: 22; Issue: 13 Linguagem: Inglês

10.1016/j.bmcl.2012.05.012

1464-3405

Takanao Sato, Kenji Sugimoto, Asuka Inoue, Shinichi Okudaira, Junken Aoki, Hidetoshi Tokuyama,

Cyclopropane Reaction Mechanisms

An enantionselective synthesis of both enantiomers of Ki16425, which possesses selective LPA antagonistic activity, was achieved. The isoxazole core was constructed by a 1,3-dipolar cycloaddition of nitrile oxide with alkyne and condensation with the optically active α-phenethyl alcohol segment, which was prepared by an enantioselective reduction of arylmethylketone. Biological evaluation of both enantiomers of Ki16425 revealed that the (R)-isomer showed much higher antagonistic activity for LPA(1) and LPA(3) receptors.