Synthesis of 3-Amino-l-CarboxymethyI-Benzodiazepine (BZA) Peptidomimetics
Replacement of key structural or binding elements of a peptide lead with nonpeptide components can improve affinity and metabolic stability (1, 2, 3, 4, 5). Such a strategy was successfully applied to the generation of potent, cell-permeable inhibitors of Ras famesyltransferase (FTase) (6,7). The central pair of amino acids in the CAAX tetrapeptide was replaced with the nonpeptide scaffold 3-methylamino-1-carboxymethyl-2,3-dihydro-5-phenyl-1H-1,4-benzodiazepin-2-one, (N-Me)BZA, shown below.
KeywordsAnhydrous Sodium Sulfate Methyl Iodide Hydrogen Fluoride Raney Nickel Cesium Carbonate
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