Auckland Uniservices Limited

Robert Forbes Anderson

William Alexander Denny

William Robert Wilson

Jeffrey Bruce Smaill

Adam Vorn Patterson

Ho Huat Lee

Amir Ashoorzadeh

Guo-Liang Lu

Michael Patrick Hay

Alexandra Marie Mowday

Stephen Michael Frazer Jamieson

Huai-Ling Annie Hsu

Andrej Maroz

Kendall Marie Carlin

The invention provides kinase inhibitors of Formula I:  Also provided are reductive prodrugs, comprising a kinase inhibitor as defined above and a reductive trigger linked directly or indirectly to a nitrogen of the kinase inhibitor. Further provided are pharmaceutical compositions, comprising the kinase inhibitors or the prodrugs, and the use of such compositions in therapy, in particular for treating cancer.

Kinase inhibitors, prodrug forms thereof and their use in therapy

The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; Ris a group of the formula &#x2014;(CH)Tr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and &#x2014;(CH)Tr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R, Rand Rmay each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R)(R)(R)N, or two of R, R, and Rmay form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R, Rand Rmay be absent and two of R, Rand Rform an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

Prodrug forms of kinase inhibitors and their use in therapy

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Auckland, New Zealand

Robert Forbes Anderson