875119-71-4Relevant academic research and scientific papers
Non-thiol farnesyltransferase inhibitors: Evaluation of different AA(X)-peptidomimetic substructures in combination with arylic cysteine replacements
Sakowski, Jacek,Boehm, Markus,Sattler, Isabel,Schlitzer, Martin
, p. 135 - 142 (2002)
In the course of our studies on non-thiol farnesyltransferase inhibitors based on the 2,5-diaminobenzophenone AAX-peptidomimetic substructure, we have developed the (4-nitrophenyl)butyryl (R1), the (2-naphthyl)acryloyl (R2), the 4-nitrocinnamoyl (R3), and the 5-(4-nitrophenyl)furylacryloyl (R4) groups as useful cysteine replacements. In this study, we combined these four groups with other AA(X)-peptidomimetic substructures (5-10: R = H) reported in the literature. The 5-(4-nitrophenyl)furylacryloyl moiety (R4) turned out to be the most useful non-thiol cysteine replacement yielding in all cases the most active inhibitors. By combination of this 5-(4-nitrophenyl)furylacryloyl moiety (R4) with the structurally simple AAX-peptidomimetics 4-aminobenzophenone (5) and 4-aminodiphenylsulfone (6) potent, readily accessible non-thiol farnesyltransferase inhibitors were obtained (IC50 = 12 nM and 10 nM).
