Cancer Research Campaign Technology Limited

Jane A Endicott

Francis Thomas Boyle

Bernard Thomas Golding

David Richard Newell

Alan H Calvert

Roger J Griffin

Nicola J Curtin

Martin E M Noble

Philip J Jewsbury

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

Jane A Endicott