Pdk-1/akt signaling inhibitors

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 231/12 (2006.01) A61K 31/415 (2006.01)

Patent

CA 2566846

A new class of phosphoinositide-dependent kinase-1 (PDK-1) inhibitors of formula (I): wherein X is selected from the group consisting of alkyl and haloalkyl; Ar is an aryl radical selected from the group consisting of phenyl, biphenyl, naphthyl, anthryl, phenanthryl, and fluorenyl; and wherein Ar is optionally substituted with one or more radicals selected from the group consisting of halo, C1 C4 alkyl, C1 C4 haloalkyl, azido, C1 C4 azidoalkyl, aryl, akylaryl, haloaryl, haloalkylaryl, and combinations thereof; and R is selected from the group consisting of nitrile, acetonitrile, ethylnitrile, propylnitrile, carboxamide, amidine, tetrazole, oxime, hydrazone, acetamidine, aminoacetamide, guanidine, and urea. Also provided are methods of using the compounds for the treatment and prevention of cancer in humans.

Nouvelle classe d'inhibiteurs de kinase-1 dépendant de phosphoïnositide (PDK-1) ayant la formule (I) dans laquelle X est sélectionné dans le groupe comprenant alkyle et haloalkyle; Ar est un radical aryle sélectionné dans le groupe comprenant phényle, biphényle, naphthyle, anthryle, phénanthryle et fluorényle; et dans lequel Ar est éventuellement substitué par un ou plusieurs radicaux sélectionnés dans le groupe comprenant halo, alkyle C¿1? C¿4?, haloalkyle C¿1? C¿4?, azido, azidoalkyle C¿1? C¿4?, aryle, akylaryle, haloaryle, haloalkylaryle et leurs combinaisons; et R est sélectionné dans le groupe constitué de nitrile, acétonitrile, éthylnitrile, propylnitrile, carboxamide, amidine, tétrazole, oxime, hydrazone, acetamidine, aminoacetamide, guanidine et urée. L'invention concerne aussi des procédés pour utiliser ces composés dans le traitement et la prévention du cancer chez les humains.

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