title: Synthesis and evaluation of substrate-mimicking cytosolic phospholipase A2 inhibitors--reducing the lipophilicity of the arachidonyl chain isostere.
abstract: The high lipophilicity of a series of cytosolic phospholipase A(2) inhibitors has been reduced by the modification of a decyloxyphenyl chain designed to mimic the arachidonyl group of the natural substrate. These changes have resulted in an improvement in the whole cell potency of the inhibitors.
authors.affiliation: Departments of Medicinal Chemistry, Molecular Biology, and Discovery BioScience, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, United Kingdom. iain.walters@astrazeneca.com
authors.forename: Iain
authors.initials: I
authors.lastname: Walters
authors.forename: Colin
authors.initials: C
authors.lastname: Bennion
authors.forename: Stephen
authors.initials: S
authors.lastname: Connolly
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Croshaw
authors.forename: Kim
authors.initials: K
authors.lastname: Hardy
authors.forename: Paul
authors.initials: P
authors.lastname: Hartopp
authors.forename: Clive G
authors.initials: CG
authors.lastname: Jackson
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: King
authors.forename: Louise
authors.initials: L
authors.lastname: Lawrence
authors.forename: Antonio
authors.initials: A
authors.lastname: Mete
authors.forename: David
authors.initials: D
authors.lastname: Murray
authors.forename: David H
authors.initials: DH
authors.lastname: Robinson
authors.forename: Linda
authors.initials: L
authors.lastname: Stein
authors.forename: Edward
authors.initials: E
authors.lastname: Wells
authors.forename: W
authors.initials: W
authors.lastname: John Withnall
mesh_terms: D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D018716:Molecular Mimicry; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2