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

Koichiro Arai

Tomohisa Toyama

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