Synthesis of 3-Amino-l-CarboxymethyI-Benzodiazepine (BZA) Peptidomimetics
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Replacement of key structural or binding elements of a peptide lead with nonpeptide components can improve affinity and metabolic stability (1 –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.
![N-[2-[4-[[6-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethyl]-2-azaspiro[3.3]heptan-2-yl]methyl]cyclohexyl]-5-(2-hydroxypropan-2-yl)-1,3-benzothiazol-6-yl]-6-(trifluoromethyl)pyridine-2-carboxamide，Moligand™，阿拉丁](https://img1.dxycdn.com/p/s14/2024/0619/785/8670042233826733081.jpg!wh200)
