180977-38-2

Upstream product

• 100959-22-6 methyl 2-bromo-4-nitrobenzoate 
• 13922-41-3 1-Naphthylboronic acid 
• 16426-64-5 2-bromo-4-nitrobenzoic acid 
• 703-55-9 1-naphthylmagnesiumbromide 

Downstream Products

• 1613316-20-3 C₄₉H₄₆N₄O₄S₂ 
• 1613316-14-5 C₂₅H₂₈N₂O₃S 
• 1613316-08-7 C₂₅H₂₆N₂O₅S 
• 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 
• 180977-42-8 4-nitro-2-naphthylbenzoyl-leucine methyl ester 
• 478909-61-4 (S)-2-(4-Amino-2-naphthalen-1-yl-benzoylamino)-4-methyl-pentanoic acid methyl ester 
• 1027488-86-3 4-methyl-2-(2-naphthalen-1-yl-4-{[(1-trityl-1H-imidazol-4-ylmethyl)-amino]-methyl}-benzoylamino)-pentanoic acid methyl ester 
• 225920-51-4 4-(N-Boc-aminomethyl)-2-(1-naphthyl)benzoylleucine methyl ester 
• 225938-41-0 2-(4-{[(1H-imidazol-4-ylmethyl)-amino]-methyl}-2-naphthalen-1-yl-benzoylamino)-4-methyl-pentanoic acid methyl ester 
• 748755-06-8 (S)-2-(4-Aminomethyl-2-naphthalen-1-yl-benzoylamino)-4-methyl-pentanoic acid methyl ester 
• 225920-50-3 4-cyano-2-(1-naphthyl)benzoylleucine methyl ester 
• 225920-49-0 4-cyano-2-naphthalen-1-yl-benzoic acid 

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.

Inhibitors of protein isoprenyl transferases

Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2—, and (i) heterocyclic-L2—; R2 is selected from (a) (b) —C(O)NH—CH(R14)—C(O)OR15, (c) (d) —C(O)NH—CH(R14)—C(O)NHSO2R16 (e) —C(O)NH—CH(R14)-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R14)—C(O)NR17R18; R3 is heterocyclic, aryl, substituted or unsubstituted cycloalkyl; R4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L1 is absent or is selected from (a) —L4—N(R5)—L5—, (b) —L4—O—L5—, (c) —L4—S(O)n—L5— (d) —L4-L6—C(W)—N(R5)—L5—, (e) —L4-L6—S(O)m—N(R5)—L5—, (f) —L4—N(R5)—C(W)—L7-L5—, (g) —L4—N(R5)—S(O)p—L7—L5—, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, and (j) optionally substituted alkynylene are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.

Potent, highly selective, and non-thiol inhibitors of protein geranylgeranyltransferase-I

The design, synthesis, and biological evaluation of a family of peptidomimetic inhibitors of protein geranylgeranyltransferase-I (PGGTase-I) are reported. The inhibitors are based on the C-terminal CAAL sequence of many geranylgeranylated proteins. Using

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.