Novel indole inhibitors of IMPDH from fragments: synthesis and initial structure-activity relationships

Rebekah E Beevers; George M Buckley; Natasha Davies; Joanne L Fraser; Francis C Galvin; Duncan R Hannah; Alan F Haughan; Kerry Jenkins; Stephen R Mack; William R Pitt; Andrew J Ratcliffe; Marianna D Richard; Verity Sabin; Andrew Sharpe; Sophie C Williams

doi:10.1016/j.bmcl.2006.01.090

Novel indole inhibitors of IMPDH from fragments: synthesis and initial structure-activity relationships

Bioorg Med Chem Lett. 2006 May 1;16(9):2539-42. doi: 10.1016/j.bmcl.2006.01.090. Epub 2006 Feb 17.

Authors

Rebekah E Beevers¹, George M Buckley, Natasha Davies, Joanne L Fraser, Francis C Galvin, Duncan R Hannah, Alan F Haughan, Kerry Jenkins, Stephen R Mack, William R Pitt, Andrew J Ratcliffe, Marianna D Richard, Verity Sabin, Andrew Sharpe, Sophie C Williams

Affiliation

¹ UCB Celltech, Granta Park, Great Abington, Cambridge, CB1 6GS, UK.

PMID: 16483773
DOI: 10.1016/j.bmcl.2006.01.090

Abstract

The elaboration of previously reported indole fragments as inhibitors of inosine monophosphate dehydrogenase (IMPDH) is described. The synthesis, in vitro inhibitory values for IMPDH II, PBMC proliferation and physicochemical properties are discussed.

MeSH terms

Biological Transport, Active / drug effects
Caco-2 Cells
Cell Proliferation / drug effects
Drug Evaluation, Preclinical
Enzyme Activation / drug effects
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
IMP Dehydrogenase / antagonists & inhibitors*
In Vitro Techniques
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology*
Leukocytes, Mononuclear / drug effects
Molecular Structure
Molecular Weight
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Indoles
IMP Dehydrogenase