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ID: ALA1137997

Journal: Bioorg Med Chem Lett

Title: Synthesis and activity of 1-aryl-1'-imidazolyl methyl ethers as non-thiol farnesyltransferase inhibitors.

Authors: Li Q, Wang GT, Li T, Gwaltney SL, Woods KW, Claiborne A, Wang X, Gu W, Cohen J, Stoll VS, Hutchins C, Frost D, Rosenberg SH, Sham HL.

Abstract: A series of imidazole-containing methyl ethers (4-5) have been designed and synthesized as potent and selective farnesyltransferase inhibitors (FTIs) by transposition of the D-ring to the methyl group on the imidazole of the previously reported FTIs 3. Several compounds such as 4h and 5b demonstrate superior enzymatic activity to the current benchmark compound tipifarnib (1) with IC(50) values in the lower subnanomolar range, while maintaining excellent cellular activity comparable to tipifarnib. The compounds are characterized as being simple, easier to make, and possess no chiral center involved.

CiteXplore: 15454229

DOI: 10.1016/j.bmcl.2004.08.011