Vernalis &r&d) Ltd.

Asahi Kasei Pharma Corporation

Vernalis Limited

Nicolas Foloppe

Takahiko Ito

Martin James Drysdale

Paul Webb

Simon Bedford

Stephen Stokes

Stuart Christopher Ray

Andrea Fiumana

Masakazu Atobe

Misato Takashima

Koichiro Arai

Tomohisa Toyama

Yu Yoshii

Daniel Paul Maddox

Andrew John Potter

A method of treating a mammal suffering from a cancer responsive to inhibition of protein kinase activity, by administering to the mammal an amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, effective to inhibit protein kinase activity, wherein the compound of formula (I) is: 

Indolyl-pyridone derivatives having checkpoint kinase 1 inhibitory activity

Compounds of formula (I) have checkpoint kinase 1 (CHK1) inhibitory activity: wherein R, R, Rand Rare independently selected from hydrogen, hydroxy, methyl, trifluoromethyl, hydroxymethyl, methoxy, trifluoromethoxy, methylamino and dimethylamino; R, and Rare independently selected from hydrogen, hydroxy, C-Calkyl, fluoro-(C-C)-alkyl, hydroxy-(C-C)-alkyl, C-Calkoxy, fluoro-(C-C)-alkoxy, hydroxy-(C-C)-alkoxy, &#x2014;N(R)&#x2014;R, -Alk-N(R)&#x2014;R, &#x2014;O-Alk-N(R)&#x2014;R, &#x2014;C(&#x2550;O)OH, carboxy-(C-C)-alkyl, or &#x2014;C(&#x2550;O)&#x2014;NH&#x2014;R; Alk is a straight or branched chain divalent C-Calkylene radical; Rand Rare independently selected from hydrogen, hydroxy, or C-Calkoxy; X is a straight chain divalent C-Calkylene radical, optionally substituted on one or more carbons by Rand/or R; W is selected from &#x2014;C(&#x2550;O)&#x2014;N(&#x2014;R)&#x2014; or &#x2014;N(&#x2014;R)&#x2014;C(&#x2550;O)&#x2014;; Y is hydrogen, C-Calkyl, C-Calkoxy, or halo; and Q is selected from optionally substituted phenyl, optionally substituted cyclohexyl, or an optionally substituted 6-membered monocyclic heteroaryl ring.

Compounds of formula (I) have checkpoint kinase 1 (CHK1) inhibitory activity: wherein R, R, Rand Rare independently selected from hydrogen, hydroxy, methyl, trifluoromethyl, hydroxymethyl, methoxy, trifluoromethoxy, methylamino and dimethylamino; R, and Rare independently selected from hydrogen, hydroxy, C-Calkyl, fluoro-(C-C)-alkyl, hydroxy-(CC)-alkyl, C-Calkoxy, fluoro-(C-C)-alkoxy, hydroxy-(C-C)-alkoxy, -AIk-N(R)&#x2014;R, -0-AIk-N(R)&#x2014;R, &#x2014;C(&#x2550;O)OH, carboxy-(C-C)-alkyl, or &#x2014;C(&#x2550;O)&#x2014;NH&#x2014;R; AIk is a straight or branched chain divalent C-Calkylene radical; Rand Rare independently selected from hydrogen, hydroxy, or C-Calkoxy; X is a straight chain divalent C-Calkylene radical, optionally substituted on one or more carbons by Rand/or R; W is selected from &#x2014;C(&#x2550;O)&#x2014;N(&#x2014;R)&#x2014; or &#x2014;N(&#x2014;R)&#x2014;C(&#x2550;O)&#x2014;; Y is hydrogen, C-Calkyl, C-Calkoxy, or halo; and Q is selected from optionally substituted phenyl, optionally substituted cyclohexyl, or an optionally substituted 6-membered monocyclic heteroaryl ring. 

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Winnersh, United Kingdom

Nicolas Foloppe