250697-56-4

Upstream product

• 98-74-8 4-Nitrobenzenesulfonyl chloride 
• 2491-18-1 (S)-methyl 2-amino-4-(methylthio)butanoate hydrochloride 
• 250697-55-3 (S)-methyl 4-(methylthio)-2-(4-nitrophenylsulfonamido)butanoate 

Downstream Products

• 250697-69-9 N-[4-(3-tert-butoxycarbonylaminopropionyl)aminophenylsulfonyl]methionine methyl ester 
• 250697-77-9 (S)-4-Methylsulfanyl-2-{4-[3-((3E,7E)-4,8,12-trimethyl-trideca-3,7,11-trienoylamino)-propionylamino]-benzenesulfonylamino}-butyric acid methyl ester 

Relevant academic research and scientific papers

Design, synthesis and early structure-activity relationship of farnesyltransferase inhibitors which mimic both the peptidic and the prenylic substrate

Inhibition of the farnesylation of ras proteins has been identified as a promising target in tumor therapy. Only a few farnesyltransferase inhibitors are bisubstrate analogues displaying features of both substrates, the farnesylpyrophosphate and the C-terminal CAAX-tetrapeptide sequence of the ras protein. These known bisubstrate analogues consist of an AAX-tripeptide and a farnesyl residue connected through various linkers. We have developed a class of novel compounds that mimic a bisubstrate inhibitor structure and that differ from the known ones by lacking peptidic or farnesylic substructures. Long chain fatty acids and aryl-substituted carboxylic acids were used as farnesyl surrogates. These structures were linked to isoleucine amide, benzoic acid amide, N-substituted aminobenzenesulfonamides and N(α)-aryl-substituted methionine derivatives, respectively, which function as AA- or AAX-mimetics. Copyright (C) 2000 Elsevier Science Ltd.

Different amino acid replacements in CAAX-tetrapeptide based peptidomimetic farnesyltransferase inhibitors

In a series of CAAX-tetrapeptide based farnesyltransferase inhibitors it has been shown that the central AA-dipeptide can be replaced by tranexamic acid, 4-aminobenzenesulfonic acid, and 3-amino-N-(2,3- dimethylphenyl)benzenesulfonamide, respectively, yielding inhibitors active in the low micromolar range. Lipophilic derivatives of these compounds showed moderate antiproliferative activity against different tumor cell lines. A promising class of peptidomimetic farnesyltransferase inhibitors was discovered through the replacement of the terminal AAX motif of the CAAX- tetrapeptide by 2-acylamino-5-aminobenzophenones.

Synthesis and evaluation of homofarnesoyl-substituted CAAX-peptidomimetics as farnesyltransferase inhibitors and antiproliferative agents

Several CAAX-peptidomimetics were linked to homofarnesoic acid via a β-alanyl spacer with the intention to obtain a novel type of bisubstrate analogue farnesyltransferase inhibitors. However, the compounds were found to be only weakly active in the farnesyltransferase inhibition assay. Nevertheless, they displayed antiproliferative activity against different tumor cell lines in the low micromolar range. Replacement of the β-alanine moiety by aspartic acid-1-methyl ester resulted in a compound which inhibited the farnesyltransferase with an IC50 of 860 nM. The corresponding free acid showed a eightfold loss in activity (IC50 = 6.9 μM).