Cyclin dependent kinase inhibitors

US6677345B1 · kind B1 · utility

Assignee

• Cancer Research Campaign Technology Limited · GB

Inventors

• Roger John Griffin · Morpeth, GB
• Alan Hilary Calvert · Birtley, GB
• Nicola Curtin · Birtley, GB
• David Richard Newell · Ryton, GB
• Bernard Thomas Golding · Newcastle upon Tyne, GB
• Jane A Endicott · Felton, GB
• Martin E M Noble · Felton, GB
• Francis Thomas Boyle · Macclesfield, GB
• Philip J Jewsbury · Grafton, GB

Key dates

• Filing date: Sep 28, 2000
• Grant date: Jan 13, 2004
• Expiry date: Sep 28, 2020

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07H19/167
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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 CHRx where Rx is H or C1-4 alkyl; D is H or NZ1Z2 where Z1 and Z2 are each independently H, C1-4 alkyl, C1-4 hydroxyalkyl, optionally substituted aryl or optionally substituted aralkyl; A is selected from H, C1-4 alkyl, C1-4 alkoxy, hydroxy, CH2(CH2)nOH (n=1-4), and NRa1Ra2 where Ra1 and Ra2 are each independently H or C1-4 alkyl; Y is or includes an optionally substituted 4- to 8-membered carbocyclic or heterocyclic ring; D′ is H or NZ3Z4 where Z3 and Z4 are each independently H, C1-4 alkyl, C1-4 hydroxyalkyl, optionally substituted aryl or optionally-substituted aralkyl; E is selected from NO, NO2, N═N—Ar where Ar is an optionally substituted aryl or optionally substituted aralkyl, NRe1Re2 or Nre1Nre2Re3 (Re1, Re2 and Re3 each being indep…