Quinazolinethiones and quinazolinediones, novel inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships

George M Buckley; Natasha Davies; Hazel J Dyke; Philip J Gilbert; Duncan R Hannah; Alan F Haughan; Caroline A Hunt; William R Pitt; Rachael H Profit; Nicholas C Ray; Marianna D Richard; Andrew Sharpe; Alicia J Taylor; Justine M Whitworth; Sophie C Williams

doi:10.1016/j.bmcl.2004.11.015

Quinazolinethiones and quinazolinediones, novel inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships

Bioorg Med Chem Lett. 2005 Feb 1;15(3):751-4. doi: 10.1016/j.bmcl.2004.11.015.

Authors

George M Buckley¹, Natasha Davies, Hazel J Dyke, Philip J Gilbert, Duncan R Hannah, Alan F Haughan, Caroline A Hunt, William R Pitt, Rachael H Profit, Nicholas C Ray, Marianna D Richard, Andrew Sharpe, Alicia J Taylor, Justine M Whitworth, Sophie C Williams

Affiliation

¹ Celltech R and D, Granta Park, Great Abington, Cambridge CB1 6GS, UK.

PMID: 15664851
DOI: 10.1016/j.bmcl.2004.11.015

Abstract

The development of a series of novel quinazolinethiones and quinazolinediones as inhibitors of inosine monophosphate dehydrogenase (IMPDH) is described. The synthesis, in vitro inhibitory values for IMPDH II and in vitro inhibitory value for PBMC proliferation are discussed.

MeSH terms

Blood Cells
Cell Proliferation / drug effects
Enzyme Inhibitors / chemical synthesis
Humans
IMP Dehydrogenase / antagonists & inhibitors*
Inhibitory Concentration 50
Ketones / chemical synthesis
Ketones / pharmacology
Monocytes / drug effects
Quinazolines / chemical synthesis*
Quinazolines / pharmacology*
Structure-Activity Relationship
Thiones / chemical synthesis
Thiones / pharmacology

Substances

Enzyme Inhibitors
Ketones
Quinazolines
Thiones
IMP Dehydrogenase
IMPDH1 protein, human