210753-55-2Relevant academic research and scientific papers
N-arlalkyl pseudopeptide inhibitors of farnesyltransferase
DeSolms, S. Jane,Giuliani, Elizabeth A.,Graham, Samuel L.,Koblan, Kenneth S.,Kohl, Nancy E.,Mosser, Scott D.,Oliff, Allen I.,Pompliano, David L.,Rands, Elaine,Scholz, Thomas H.,Wiscount, Catherine M.,Gibbs, Jackson B.,Smith, Robert L.
, p. 2651 - 2656 (2007/10/03)
Inhibitors of Ras protein farnesyltransferrase are described which are reduced pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that signals farneslation. Reduction of the carbonyl groups linking the first three residues of the tetrapeptide leads to active inhibitors which are chemically unstable. Stability can be restored by alkylating the central amine of the tetrapeptide. Studies of the SAR of these alkylated pseudopeptides with concominant modification of the side of the third residue led to 2(S)-(2(S)-{[2(S)-2(R)-amino-3-mercaptopropylamino)-3-(S)- methylpentyl]napthalen-1-ylmethylamino}acetylamino)-4-methylsulfanylbutyric acid (11), a subnanomolar inhibitor. The methyl ester (10) of this compound exhibited submicromolar activity in the processing assay and selectively inhibited anchorage-independent growth of Rat1 cells transformed by v-ras at 2.5 - 5 μ.
