| Abstract
| - The benzodiazepinedione class of non-peptidal GPIIbIIIaantagonists has been modified to allowthe isolation of noninterconverting rotational isomers, oratropisomers, with the aim ofexamining their structure−activity relationships as compared toactive RGD-containing peptidesand other non-peptidal antagonists. Resolution of theseantagonists was accomplished by theintroduction of a tert-butyl group at N1 and a chlorine atC9 on the 3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione nucleus and enantiospecific substitution on theβ-alanine side chainattached to N4. The relative configuration was determined bysingle-crystal X-ray analysis.Further, conformational analyses using abinitio calculations were performed to assesstheconformational preferences about the β-alanine side chain. Thedata support a goodtopographical correlation between the benzodiazepinedione class ofantagonists and the “cupped”presentation of the RGD tripeptide sequence found in the cyclic peptideG4120. The relationshipbetween these compounds with other peptidal and non-peptidalantagonists is discussed.
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