151978-67-5Relevant articles and documents
Mono-N-Alkylation of Anthranylamides via Quinazolinones. An Efficient Synthesis of G5598, A Benzodiazepine Dione GpIIbIIIa Antagonist
Webb, Robert R., II,Barker, Peter L.,Baier, Mark,Reynolds, Mark E.,Robarge, Kirk D.,et al.
, p. 2113 - 2116 (1994)
The mono-N-alkylation of an anthranylamide derivative via the reductive ring opening of a quinazolinone precursors, enables the synthesis of benzodiazepine dione derivative G5598, a potent inhibitor of the in vitro binding of GpIIbIIIa to fibrinogen.
From peptide to non-peptide. 2. The de novo design of potent, non-peptidal inhibitors of platelet aggregation based on a benzodiazepinedione scaffold
McDowell, Robert S.,Blackburn, Brent K.,Gadek, Thomas R.,McGee, Lawrence R.,Rawson, Thomas,Reynolds, Mark E.,Robarge, Kirk D.,Somers, Todd C.,Thorsett, Eugene D.,Tischler, Maureen,Webb II, Robert R.,Venuti, Michael C.
, p. 5077 - 5083 (2007/10/02)
Earlier studies of peptides containing the arginine-glycine-aspartic acid (RGD) sequence led to the development of a structural model describing the three-dimensional presentation required for RGD-mediated inhibition of glycoprotein IIbIIIa/fibrinogen binding. We describe here the use of that structural model to design a rigid, non-peptidal lead series that reproduces the topography of the peptide backbone using a benzodiazepinedione scaffold. This scaffold is used to synthesize novel molecules which are highly potent inhibitors of platelet aggregation and which possess improved bioavailability. The importance of shape as a design criterion is demonstrated by constructing molecules that present alternative topographies; these molecules are shown to be significantly less potent.
