Bioorganic & Medicinal Chemistry Letters 2010-02-01

A study of the effects of substituents on the selectivity of the binding of N-arylaminomethylene malonate inhibitors to DHODH.

Deborah Cowen, Paul Bedingfield, Glenn A McConkey, Colin W G Fishwick, A Peter Johnson

Index: Bioorg. Med. Chem. Lett. 20(3) , 1284-7, (2010)

Full Text: HTML

Abstract

A series of mono- and di-substituted N-arylaminomethylene malonates have been used to probe the potential of utilizing additional H-bonding contacts in the ubiquinone binding channel, for selective inhibition between either human or Plasmodium DHODH. Altered 'head' group functionalities have been utilized in order to probe the role of specific functionalities within the inhibitors in terms of enzyme affinity and selectivity.Copyright (c) 2009 Elsevier Ltd. All rights reserved.