52084-06-7

Upstream product

• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 371-40-4 4-fluoroaniline 
• 352-34-1 4-fluoro-1-iodobenzene 
• 5241-58-7 L-Phenylalanine amide 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 63-91-2 L-phenylalanine 
• 5123-55-7 Nα-phthaloyl-L-phenylalanine 
• 32150-91-7 phthaloyl-L-phenylalanyl chloride 

Downstream Products

• 1027402-84-1 {(R)-1-[(S)-1-(4-Fluoro-phenylcarbamoyl)-2-phenyl-ethylcarbamoyl]-3-methyl-butyl}-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Bifunctional Naphthoquinone Aromatic Amide-Oxime Derivatives Exert Combined Immunotherapeutic and Antitumor Effects through Simultaneous Targeting of Indoleamine-2,3-dioxygenase and Signal Transducer and Activator of Transcription 3

Indoleamine-2,3-dioxygenase 1 (IDO1) and signal transducer and activator of transcription 3 (STAT3) are important targets in the tumor microenvironment for cancer therapy. In the present study, a set of naphthoquinone aromatic amide-oxime derivatives were designed, which stimulated the immune response via IDO1 inhibition and simultaneously displayed powerful antitumor activity against three selected cancer cell lines through suppressing STAT3 signaling. The representative compound 8u bound effectively to IDO1, with greater inhibitory activity relative to the commercial IDO1 inhibitor 4-amino-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide (IDO5L) in addition to the efficient suppression of nuclear translocation of STAT3. Consistently, in vivo assays demonstrated a higher antiproliferative activity of compound 8u in both wild-type B16-F10 isograft tumors and an athymic HepG2 xenograft model relative to 1-methyl-l-tryptophan (1-MT) and doxorubicin (DOX). This bifunctional compound with dual immunotherapeutic and anticancer efficacy may represent a new generation of highly efficacious drug candidates for cancer therapy.

Caproamide derivatives, its preparation method, intermediate and application

The invention discloses a caproamide derivative represented by formula A or a pharmaceutically acceptable salt thereof, wherein R1 is H or halogen; R2 is halogen, or C1-C4 alkyl, C1-C4 alkoxy, or a C3-C7 heterocyclic ring, the number of heteroatom in the heterocyclic ring is 1-3, and the heteroatom is nitrogen and/or oxygen; R0 is benzyl, substituted benzyl or C4 alkyl, and a substituent of substituted benzyl is C1-C3 alkyl. The invention also discloses a preparation method, an intermediate and an application of the caproamide derivative. The caproamide derivative provided by the invention has effective and better antibacterial function, and has higher application value in the medical field.

Synthesis and antitumor activities of novel dipeptide derivatives derived from dehydroabietic acid

A series of dipeptide derivatives from dehydroabietic acid were designed and synthesized as novel antitumor agents. The antitumor activities screening indicated that many compounds showed moderate to high levels of inhibition activities against NCI-H460, HepG2, SK-OV-3, BEL-7404, HeLa and HCT-116 cancer cell lines and that some displayed more potent inhibitory activities than commercial anticancer drug 5-fluorouracil. The mechanism of representative compound 7b was studied by AO/EB staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which exhibited that the compound could induce apoptosis in HeLa cells. Further investigation showed that compound 7b induced apoptosis of HeLa cells through a mitochondrial pathway.

Synthesis of chiral amino acid anilides by ligand-free copper-catalyzed selective N-arylation of amino acid amides

An atom-economic, practical and cost-effective protocol for synthesis of chiral amino acid anilides via ligand-free copper-catalyzed selective C-N cross coupling of chiral amino acid amides and aryl halides, hetereoaryl halides and a vinyl bromide has been developed. No racemization occurred during the C-N coupling. A plausible mechanism is proposed. Copyright

Chymotrypsin inhibitory conformation induced by amino acid side chain-side chain intramolecular CH/π interaction

Dipeptide amides H-D-Leu-Phe-NH-R have been found to assume a conformation induced by the CH/π interaction and to inhibit chymotrypsin strongly. A series of benzyl amide derivatives H-D-Leu-Phe-NH-[CH2]n-C6H5 (n = 0-4) have been assayed for chymotrypsin. They inhibit the enzyme in a competitive manner and the highest inhibition is achieved by the amide of n = 1 (Ki = 3.6 × 10-6 M). The activity enhancement is dependent upon the length of methylene chain, not upon the increase in molecular hydrophobicity, indicating the presence of an optimal distance between dipeptide backbone and C-terminal phenyl group for chymotrypsin inhibition. The C-terminal phenyl group has been found to interact with chymotrypsin stereospecifically. The R-isomer of H-D-Leu-Phe-NH-CH(CH3)-C6H5 is as active as the benzyl amide, while the S-isomer is about twenty-fold less active. When the fluorine atom is introduced at a para-position of the C-terminal phenyl group, the resulting dipeptide H-D-Leu-Phe-NH-CH2-C6H4F-p exhibits about six-times increased inhibitory activity (Ki = 6.1 × 107 M; this dipeptide is one of the most potent chymotrypsin inhibitors to date). 1H NMR conformational analyses of these dipeptide amide derivatives show the CH/π interaction between D-Leu-isobutyl and Phe-phenyl as a key structural element for chymotrypsin inhibition. These structural examinations strongly suggest that in the inhibitory conformation the C-terminal phenyl group fits the chymotrypsin S1 site, while the hydrophobic core constructed by D-Leu-Phe CH/π interaction fits the chymotrypsin S2 or S1′ site.