W. Kinney
Feb 1, 1996
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Journal
Phosphorus Sulfur and Silicon and The Related Elements
Abstract
Abstract The 3,4-diamino-3-cyclobutene-1,2-dione group was utilized as a unique α-amino carboxylic acid bioisostere in a series of in vivo active NMDA antagonists, which have potential as neuroprotectants. In order to investigate SAR in this series, a new free radical approach to alkyl substituted 3-cyclobutene-1,2-diones was developed utilizing 3-isopropozy-4-tributyltin-3-cyclobutene-1,2-dione (Liebeskind's reagent). This methodology also allowed access to amino acids glycine, β-alanine, and GABA substituted with the 3-hydroxy-3-cyclobutene-1,2-dione group, which we had shown to be a carboxylic acid or tetrazole bioisostere in a series of angiotensin-II antagonists. The orally active hydroxycyclo-butenedione derivative was prepared by a palladium catalyzed Stille cross-coupling of an iodobiphenyl moiety with Liebeskind's reagent.