Efficient synthesis of 3-aminocyclobut-2-en-1-ones: squaramide surrogates as potent VLA-4 antagonists.
A novel series of uniquely functionalized 3-aminocyclobut-2-en-1-ones has been prepared by facile condensation of a variety of cyclobuta-1,3-diones with a phenylalanine-derived primary amine. These systems subsequently lend themselves to substitution at C-2 by reaction with a variety of electrophilic reagents including N-halosuccinimides, sulfenyl chlorides, and Eschenmoser's salt. Compounds from this novel series are potent antagonists of VLA-4. [reaction: see text]
Brand
Stephen
S
Medicinal Chemistry, Celltech Group plc, 216 Bath Road, Slough SL1 4EN, UK.
de Candole
Benjamin C
BC
Brown
Julien A
JA
D003503:Cyclobutanes / Q000737:chemistry* / Q000494:pharmacology*; D007202:Indicators and Reagents; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives
D003503:Cyclobutanes; D007202:Indicators and Reagents; D039041:Integrin alpha4beta1; D007659:Ketones; D010649:Phenylalanine