Squaric acid derivatives as VLA-4 integrin antagonists.
SAR studies aimed at improving the rate of clearance by the incorporation of a 3,4-diamino-3-cyclobutene-1,2-dione group as an amino acid isostere in a series of VLA-4 integrin antagonists are described.
Porter
John R
JR
Celltech R&D Ltd, 216 Bath Road, Slough SL1 4EN, UK. john.porter@celltechgroup.com
Archibald
Sarah C
SC
Childs
Kirstie
K
Critchley
David
D
Head
John C
JC
Linsley
Janeen M
JM
Parton
Ted A H
TA
Robinson
Martyn K
MK
Shock
Anthony
A
Taylor
Richard J
RJ
Warrellow
Graham J
GJ
Alexander
Rikki P
RP
Langham
Barry
B
D000588:Amines / Q000737:chemistry; D000818:Animals; D018926:Anti-Allergic Agents / Q000037:antagonists & inhibitors*; D003503:Cyclobutanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins / Q000037:antagonists & inhibitors*; D008657:Metabolic Clearance Rate; D051381:Rats; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors*; D016029:Receptors, Very Late Antigen; D013329:Structure-Activity Relationship
D000588:Amines; D018926:Anti-Allergic Agents; D003503:Cyclobutanes; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; C030042:squaric acid