180977-37-1

Upstream product

• 703-55-9 1-naphthylmagnesiumbromide 
• 100959-22-6 methyl 2-bromo-4-nitrobenzoate 
• 16426-64-5 2-bromo-4-nitrobenzoic acid 
• 180977-38-2 4-nitro-2-(1-naphthyl)benzoic acid methyl ester 
• 13922-41-3 1-Naphthylboronic acid 

Downstream Products

• 180977-42-8 4-nitro-2-naphthylbenzoyl-leucine methyl ester 
• 180977-39-3 N-[4-nitro-2-(1-naphthyl)benzoyl]-methionine methyl ester 
• 1613316-08-7 C₂₅H₂₆N₂O₅S 
• 1613316-20-3 C₄₉H₄₆N₄O₄S₂ 
• 1613316-14-5 C₂₅H₂₈N₂O₃S 
• 1613316-26-9 C₃₀H₃₂N₄O₄S₂ 
• 1613315-69-7 C₂₇H₂₆N₄O₄S₂ 
• 180977-43-9 (S)-2-[4-((R)-2-tert-Butoxycarbonylamino-3-tritylsulfanyl-propylamino)-2-naphthalen-1-yl-benzoylamino]-4-methyl-pentanoic acid methyl ester 
• 478909-61-4 (S)-2-(4-Amino-2-naphthalen-1-yl-benzoylamino)-4-methyl-pentanoic acid methyl ester 
• 180977-40-6 N[4-[N-[2(R)-(tert-butoxycarbonyl)amino-3-(triphenylmethyl)thio]propyl]amino-2-(1-naphthyl)benzoyl]-methionine methyl ester 
• 191102-99-5 (S)-2-(4-Amino-2-naphthalen-1-yl-benzoylamino)-4-methylsulfanyl-butyric acid methyl ester 

Relevant academic research and scientific papers

Farnesyltransferase inhibitors: CAAX mimetics based on different biaryl scaffolds

Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed as farnesyltransferase (FTase) inhibitors (FTIs) by replacing AA with o-aryl or o-heteroaryl substituted p-hydroxy- or p-aminobenzoic acid, while maintaining the replacement of C with 1,4-benzodioxan-2-ylmethyl or 2-amino-4- thiazolylacetyl residue as in previous CAAX mimetics. Both FTase inhibition and antiproliferative effect were showed by two thiazole derivatives, namely those with 1-naphthyl (10 and 10a) or 3-furanyl (15 and 15a) in the central spacer, and by the benzodioxane derivative with 2-thienyl (6 and 6a) in the same position. Accumulation of unprenylated RAS was demonstrated in cells incubated with 15a. Consistently with FTIs literature, such results delineate the biaryl scaffold not only as a spacer but also as a sensible area of these mimetic molecules, where modifications at the branching aromatic ring are not indifferent and should be matter of further investigation.

Probing the hydrophobic pocket of farnesyltransferase: Aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors

Cysteine farnesylation at the carboxylate terminal tetrapeptide CAAX of Ras protein is catalyzed by farnesyltransferase. This lipid modification is necessary for regulatory function of both normal and oncogenic Ras. The high frequency of Ras mutation in human cancers has prompted an intensive study on finding ways of controlling oncogenic Ras function. Inhibition of farnesyltransferase is among the most sought after targets for cancer chemotherapy. We report here the design, synthesis and biological characterization of a series of peptidomimetics as farnesyltransferase inhibitors. These compounds are extremely potent towards farnesyltransferase with IC50 values ranging from subnanomolar to low nanomolar concentrations. They have a high selectivity for farnesyltransferase over the closely related geranylgeranyltransferase-I. Structure-activity relationship studies demonstrated that a properly positioned hydrophobic group significantly enhanced inhibition potency, reflecting an improved complementarity to the large hydrophobic pocket in the CAAX binding site. Copyright (C) 1999 Elsevier Science Ltd.

Selective inhibition of type-I geranylgeranyltransferase in vitro and in whole cells by CAAL peptidomimetics

In this paper we describe the synthesis of a family of CAAL peptidomimetics as GGTase-I inhibitors. These inhibitors lack the central dipeptide AA in the key CAAL carboxy terminal sequence of geranylgeranylated proteins and are more selective for GGTase-I over FTase. In whole cells, these compounds are very potent inhibitors of the processing of the geranylgeranylated protein Rap1A without affecting the farnesylated protein H-Ras. One derivative, GGTI-298, inhibited cell division by blocking cells in the G1 phase of the cell cycle.