title: Furanyl-1,3-thiazol-2-yl and benzoxazol-5-yl acetic acid derivatives: novel classes of heparanase inhibitor.
abstract: Using a furanylthiazole acetic acid as a starting point, a novel series of benzoxazol-5-yl acetic acid derivatives have been identified as heparanase inhibitors. Several compounds possess an IC50 of approximately 200 nM against heparanase, for example, trans 2-[4-[3-(3,4-dichlorophenylamino)-3-oxo-1-propenyl]-2-fluorophenyl]benzoxazol-5-yl acetic acid (16e). Several of the compounds show anti-angiogenic properties. Improvement to the DMPK profile of compounds has provided compounds of potential use in in vivo models.
authors.affiliation: Department of Medicinal Chemistry, Celltech R&D Ltd, 4-10 The Quadrant, Abingdon Science Park, Abingdon, Oxfordshire OX14 4YS, UK.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Courtney
authors.forename: Philip A
authors.initials: PA
authors.lastname: Hay
authors.forename: Richard T
authors.initials: RT
authors.lastname: Buck
authors.forename: Claire S
authors.initials: CS
authors.lastname: Colville
authors.forename: David J
authors.initials: DJ
authors.lastname: Phillips
authors.forename: David I C
authors.initials: DI
authors.lastname: Scopes
authors.forename: Faye C
authors.initials: FC
authors.lastname: Pollard
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Page
authors.forename: James M
authors.initials: JM
authors.lastname: Bennett
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Hircock
authors.forename: Edward A
authors.initials: EA
authors.lastname: McKenzie
authors.forename: Maina
authors.initials: M
authors.lastname: Bhaman
authors.forename: Robert
authors.initials: R
authors.lastname: Felix
authors.forename: Colin R
authors.initials: CR
authors.lastname: Stubberfield
authors.forename: Paul R
authors.initials: PR
authors.lastname: Turner
mesh_terms: D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000097:blood; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000099175:Heparanase
chemical_list: D000085:Acetates; D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D005966:Glucuronidase; D013844:Thiazoles; D000099175:Heparanase