Cancer Research Technology Limited

The Institute of Cancer Research: Royal Cancer Hospital

Spyridon Linardopoulos

Vassilios Bavetsias

Edward McDonald

Julian Blagg

Keith Jones

Matthew D Cheeseman

Amir Faisal

Olivier Remi Barbeau

Andrew Kalusa

Andrew S Moore

Matthew David Cheeseman

Edward Macdonald

The present invention provides compounds of formula (I) and pharmaceutically acceptable salts, hydrates and solvates thereof for use in the treatment of cancer: 

Fused heterocyclic compounds and their use

The present invention relates to compounds of formula I: wherein Rand Rare as defined herein, or a pharmaceutically acceptable salt or solvate thereof. The compounds of formula I are inhibitors of aurora kinase and/or FLT3. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which aurora kinase and/or FLT3 activity is implicated. 

Pharmaceutically active compounds

Compounds of formula (I), are aurora kinase inhibitors: wherein X is &#x2014;N&#x2014;, &#x2014;CH2-N&#x2014;, &#x2014;CH2-CH&#x2014;, or &#x2014;CH&#x2014;; R1 is a radical of formula (IA) wherein Z is &#x2014;CH2-, &#x2014;NH&#x2014;, -0-, &#x2014;S(O)&#x2014; &#x2014;S&#x2014;, &#x2014;S(O)2 or a divalent monocyclic carbocyclic or heterocyclic radical having 3-7 ring atoms; Alk is an optionally substituted divalent C1-C6 alkylene radical; A is hydrogen or an optionally substituted monocyclic carbocyclic or heterocyclic ring having 5-7 ring atoms; r, s and t are independently 0 or 1, provided that when A is hydrogen then at least one of r and s is 1; R2 is halogen, &#x2014;CN, &#x2014;CF3, &#x2014;OCH3, or cyclopropyl; and R3 is a radical of formula (IB) wherein Q is hydrogen or an optionally substituted phenyl or monocyclic heterocyclic ring with 5 or 6 ring atoms; Z&It;1> is &#x2014;S&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;S(O)2-, &#x2014;O&#x2014;, &#x2014;SO2NH&#x2014;, &#x2014;NHSO2-, NHC(&#x2550;O)NH, &#x2014;NH(C&#x2550;S)NH&#x2014;, Or &#x2014;N(R4)&#x2014; wherein R4 is hydrogen, C1-C3 alkyl, cycloalkyl, or benzyl; and Alk&It;1> and Alk&It;2> are, independently, optionally substituted divalent C1-C3 alkylene radicals; and m, n and p are independently 0 or 1.

Enzyme inhibitors

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Sutton, United Kingdom

Spyridon Linardopoulos