Furanyl-1,3-thiazol-2-yl and benzoxazol-5-yl acetic acid derivatives: novel classes of heparanase inhibitor.
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.
Courtney
Stephen M
SM
Department of Medicinal Chemistry, Celltech R&D Ltd, 4-10 The Quadrant, Abingdon Science Park, Abingdon, Oxfordshire OX14 4YS, UK.
Hay
Philip A
PA
Buck
Richard T
RT
Colville
Claire S
CS
Phillips
David J
DJ
Scopes
David I C
DI
Pollard
Faye C
FC
Page
Martin J
MJ
Bennett
James M
JM
Hircock
Margaret L
ML
McKenzie
Edward A
EA
Bhaman
Maina
M
Felix
Robert
R
Stubberfield
Colin R
CR
Turner
Paul R
PR
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
D000085:Acetates; D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D005966:Glucuronidase; D013844:Thiazoles; D000099175:Heparanase