Synthesis and biological evaluation of nonpeptide integrin antagonists containing spirocyclic scaffolds.
Analogues of isoxazoline alpha(v)beta(3) antagonist 1 designed to further restrict the four carbon alkyl tether were prepared by incorporating two spirocyclic scaffolds, 1-oxa-2-azaspiro[4,5]dec-2-ene and 1-oxa-2,7-diazaspiro[4,4]non-2-ene. Additional optimization provided potent antagonists of both alpha(v)beta(3) and alpha(5)beta(1) which are selective over GPIIb/IIIa.
Smallheer
Joanne M
JM
Bristol-Myers Squibb Company, Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
Weigelt
Carolyn A
CA
Woerner
Francis J
FJ
Wells
Jennifer S
JS
Daneker
Wayne F
WF
Mousa
Shaker A
SA
Wexler
Ruth R
RR
Jadhav
Prabhakar K
PK
D001665:Binding Sites / Q000502:physiology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism
D007093:Imidazoles; D016023:Integrins