Cancer Research Campaign Technology Limited

Cancer Research Technology Limited

Martin E M Noble

Bernard Thomas Golding

David Richard Newell

Francis Thomas Boyle

Alan H Calvert

Roger J Griffin

Nicola J Curtin

Jane A Endicott

Philip J Jewsbury

Roger John Griffin

Ian Robert Hardcastle

Per Kallblad

John Lunec

Hendrika Maria Gerarda Willems

A compound of formula or a prodrug and/or a pharmaceutically acceptable salt thereof, wherein X is O, N or S; Ris hydrogen, halo, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylamine, alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroaralkyl; Ris hydrogen, halo, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted hydroxyalkyl substituted or unsubstituted alkylamine, alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroalkyl; Ris hydrogen, halo, hydroxy, substituted or unsubstituted alloy substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylamine alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroalkyl; and R-R, is used to represent groups R, R, Rand Rwhich are H, OH, alkyl, alkoxy, alkylamine, hydroxyalkyl, halo, CF, NH, NO, COOH, C&#x2550;O.

Isoindolin-1-one derivatives

A range is disclosed of pyrimidine derivatives (I) which can act as inhibitors of cyclin dependent kinases (CDK's) and which thereby can provide useful therapeutic compounds for use in treatment of tumours or other cell proliferation disorders. The compounds of this invention bind to CDK molecules in a manner that appears to differ from that of known CDK inhibitors such as olomoucine and roscovitine. In formula (I), X is O, S or CHR where R is H or C alkyl; D is H or NZ Z where Z and Z are each independently H, C alkyl, C hydroxyalkyl, optionally substituted aryl or optionally substituted aralkyl; A is selected from H, C alkyl, C alkoxy, hydroxy, CH (CH ) OH (n&equals;1-4), and NR R where R and R are each independently H or C alkyl; Y is or includes an optionally substituted 4- to 8-membered carbocyclic or heterocyclic ring; D&prime; is H or NZ Z where Z and Z are each independently H, C alkyl, C hydroxyalkyl, optionally substituted aryl or optionally-substituted aralkyl; E is selected from NO, NO , N&boxH;N&mdash;Ar where Ar is an optionally substituted aryl or optionally substituted aralkyl, NR R or Nr Nr R (R , R and R each being independently H, C alkyl, C hydroxyalkyl, an optionally substituted aryl or an optionally substituted aralkyl), C(R )&boxH;U (R being hydrogen, C alkyl or substituted alkyl, e.g. hydroxyalkyl, or an unsubstituted or substituted aryl or aralkyl, e.g. benzyl, and U being selected from O, Nr &prime;, NOR &prime; and N&mdash;NR &prime;R &Prime; where R &prime; and R &Prime; are each independently H, C alkyl or CONH ), T, CH T, CHT and CT , where T is a halide I, Br, Cl or F.

Cyclin dependent kinase inhibitors

Method of treating a tumour or other cell proliferation disorder which comprises administering an effective amount of a purine compound which inhibits cyclic dependent kinase activity. Novel purine compounds and pharmaceutical compositions are also disclosed.

Cyclin dependent kinase inhibiting purine derivatives

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Oxford, United Kingdom

Martin E M Noble