6401-63-4

Upstream product

• 3005-89-8 ethyl N-benzyloxycarbonyl-L-leucyl-L-phenylalaninate 
• 10473-38-8 N-(benzyloxycarbonyl)-L-leucyl-L-phenylalanine methyl ester 
• 13171-96-5 Cbz-Leu-Phe-NH₂ 
• 6401-57-6 CBZ-Leu-Phe-OC(CH₃)3 
• 2072-92-6 Z-L-Leu-L-Phe-PNP 
• 2018-66-8 Z-Leu-OH 
• 63-91-2 L-phenylalanine 
• 15100-75-1 L-phenylalanine tert-butyl ester hydrochloride 
• 3081-24-1 H-Phe-OEt 
• 76863-45-1 (S)-benzyl (1-azido-4-methyl-1-oxopentan-2-yl)carbamate 
• 67-56-1 methanol 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 

Downstream Products

• 3063-05-6 Leu-Phe-OH 
• 3867-62-7 N-benzyloxycarbonyl-leucyl=>phenylalanyl=>glycine ethyl ester 
• 66013-86-3 Z-Leu-Phe-Phe-OMe 
• 2073-67-8 Z-S-Leu-S-Phe-S-Val-OtBu 
• 188837-71-0 Oxalic acid (E)-2-((S)-2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-1-ethoxycarbonyl-3-phenyl-propenyl ester ethyl ester 
• 150831-74-6 [(S)-1-((S)-1-Benzyl-3-diazo-2-oxo-propylcarbamoyl)-3-methyl-butyl]-carbamic acid benzyl ester 
• 199006-16-1 [(S)-1-((S)-1-{(E)-3-Cyano-1-[2-(trityl-carbamoyl)-ethyl]-allylcarbamoyl}-2-phenyl-ethylcarbamoyl)-3-methyl-butyl]-carbamic acid benzyl ester 
• 211869-49-7 (S)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-6-(trityl-carbamoyl)-hexanoic acid ethyl ester 
• 199005-84-0 [(S)-1-((S)-1-{(E)-(S)-3-Dimethylcarbamoyl-1-[2-(trityl-carbamoyl)-ethyl]-allylcarbamoyl}-2-phenyl-ethylcarbamoyl)-3-methyl-butyl]-carbamic acid benzyl ester 
• 199003-72-0 (E)-(S)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-6-(trityl-carbamoyl)-hex-2-enoic acid ethyl ester 
• 199006-18-3 [(S)-1-((S)-1-{(E)-(S)-3-Ethylcarbamoyl-1-[2-(trityl-carbamoyl)-ethyl]-allylcarbamoyl}-2-phenyl-ethylcarbamoyl)-3-methyl-butyl]-carbamic acid benzyl ester 
• 199005-82-8 [(S)-3-Methyl-1-((S)-1-{(E)-(S)-4-oxo-4-pyrrolidin-1-yl-1-[2-(trityl-carbamoyl)-ethyl]-but-2-enylcarbamoyl}-2-phenyl-ethylcarbamoyl)-butyl]-carbamic acid benzyl ester 
• 211869-50-0 [(S)-1-((S)-1-{(E)-(S)-4-(2,5-Dihydro-pyrrol-1-yl)-4-oxo-1-[2-(trityl-carbamoyl)-ethyl]-but-2-enylcarbamoyl}-2-phenyl-ethylcarbamoyl)-3-methyl-butyl]-carbamic acid benzyl ester 

Relevant academic research and scientific papers

A new class of α-ketoamide derivatives with potent anticancer and anti-SARS-CoV-2 activities

Inhibitors of the proteasome have been extensively studied for their applications in the treatment of human diseases such as hematologic malignancies, autoimmune disorders, and viral infections. Many of the proteasome inhibitors reported in the literature target the non-primed site of proteasome's substrate binding pocket. In this study, we designed, synthesized and characterized a series of novel α-keto phenylamide derivatives aimed at both the primed and non-primed sites of the proteasome. In these derivatives, different substituted phenyl groups at the head group targeting the primed site were incorporated in order to investigate their structure-activity relationship and optimize the potency of α-keto phenylamides. In addition, the biological effects of modifications at the cap moiety, P1, P2 and P3 side chain positions were explored. Many derivatives displayed highly potent biological activities in proteasome inhibition and anticancer activity against a panel of six cancer cell lines, which were further rationalized by molecular modeling analyses. Furthermore, a representative α-ketoamide derivative was tested and found to be active in inhibiting the cellular infection of SARS-CoV-2 which causes the COVID-19 pandemic. These results demonstrate that this new class of α-ketoamide derivatives are potent anticancer agents and provide experimental evidence of the anti-SARS-CoV-2 effect by one of them, thus suggesting a possible new lead to develop antiviral therapeutics for COVID-19.

Application of proteasome inhibitor in inhibition of novel coronavirus

The invention provides application of a proteasome inhibitor in inhibition of a novel coronavirus or preparation of novel coronavirus inhibitors. The proteasome inhibitor has a structure represented by a formula (I) or isomers, pharmaceutically acceptable salts thereof and prodrugs thereof. According to the application, by applying the proteasome inhibitor to inhibition of the novel coronavirus, good inhibiting activity is obtained, and a novel treatment way of think is provided for diseases such as pneumonia caused by the novel coronavirus.

Convenient green preparation of dipeptides using unprotected α-amino acids

Dipeptides and amides were obtained in high yields from N-carbobenzyloxy α-amino acids and 3-phenylpropanoic acid with unprotected α-amino acids via the corresponding mixed carbonic carboxylic anhydrides using ethyl chloroformate and triethylamine by an ecological and convenient method in which the protection of C-terminals is not needed.

Synthesis, bioactivity, docking and molecular dynamics studies of furan-based peptides as 20s proteasome inhibitors

Proteasome inhibitors are promising compounds for a number of therapies, including cardiovascular and eye diseases, diabetes, and cancers. We previously reported a series of furanbased peptidic inhibitors with moderate potencies against the proteasome b5 subunit, hypothesizing that the C-terminal furyl ketone motif could form a covalent bond with the catalytic residue, threonine 1. In this context, we describe further optimizations of the furan-based peptides, and a series of dipeptidic and tripeptidic inhibitors were designed and synthesized, aiming at improved potency and better solubility. Most of the tripeptidic inhibitors demonstrated improved potency and selectivity as b5 subunit inhibitors in both enzymatic and cellular assays, and good antineoplastic activities in various tumor cell lines were also observed. However, no inhibitory effects were observed for the dipeptidic compounds, which led us to presume that a noncovalent binding mode is adopted. Docking studies and molecular dynamics simulations were carried out to verify this presumption, with results showing that the distance between the furyl ketone motif and Thr1 is slightly too long to form covalent bond.

One-step C-terminal deprotection and activation of peptides with peptide amidase from stenotrophomonas maltophilia in neat organic solvent

Chemoenzymatic peptide synthesis is a rapidly developing technology for cost effective peptide production on a large scale. As an alternative to the traditional C→N strategy, which employs expensive N-protected building blocks in each step, we have investigated an N→C extension route that is based on activation of a peptide C-terminal amide protecting group to the corresponding methyl ester. We found that this conversion is efficiently catalysed by Stenotrophomonas maltophilia peptide amidase in neat organic media. The system excludes the possibility of internal peptide cleavage as the enzyme lacks intrinsic protease activity. The produced peptide methyl ester was used for peptide chain extension in a kinetically controlled reaction by a thermostable protease.

Endoperoxide carbonyl falcipain 2/3 inhibitor hybrids: Toward combination chemotherapy of malaria through a single chemical entity

We extend our approach of combination chemotherapy through a single prodrug entity (O'Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonyl-masking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action: iron(II) decomposition releases the carbonyl protease inhibitor and potentially cytotoxic C-radical species in tandem. Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.

Diastereoselective specificity for the hydrolysis of dipeptide esters in aqueous media

The diastereoselectivity for the hydrolysis of p-methoxycarbonylphenyl N-(benzyloxycarbonyl)-D(L)-phenylalanyl-L-leucinate in aqueous solution was inverted by changing concentrations of the substrates or the reaction temperature. The monomer-aggregate transition operated on the LL-substrate, which was suggested by the spectroscopic measurements, seems to be responsible for such behavior.

ARYLOXY AND ARYLACYLOXY METHYL KETONES AS THIOL PROTEASE INHIBITORS

Thiol protease inhibitors are disclosed having the formula: STR1 or an optical isomer thereof, or a pharmaceutically acceptable salt thereof, wherein:n is 0 or 1;m is 0, 1 or 2;X is H or an N-protecting group; each Y is independently an optionally protected α-amino acid residue;R is an optionally protected α-amino acid side chain that is H or CH 3 or that is bonded to the α-carbon atom to which it is attached by a methylene, methine or phenyl radical; andR' is optionally substituted aryl.

Method for reductive elimination of protecting groups

The invention provides a novel and efficient method for the elimination of protecting groups, e.g. benzyloxycarbonyl group, from a protected amino acid, peptide or derivative thereof having at least one functional group protected by a protecting group, e.g. a lower alkyl ester of N-benzyloxycarbonyl-α-L-aspartyl-L-phenylalanine by catalytic hydrogen reduction to produce free amino acid, peptide or derivative thereof. In contrast to the conventional procedures in which the reaction is carried out in a solvent dissolving both the starting compound and the product compound or a solvent dissolving the starting compound but not dissolving the product compound, the inventive method utilizes a binary two-phase reaction medium composed of water and an organic solvent not freely miscible with water such as toluene. The reaction takes place in the organic phase containing the starting compound dissolved and the catalyst dispersed therein whereas the reaction product which is water-soluble is smoothly and successively transferred into the aqueous phase so that advantages are obtained in the unexpectedly high yield of the product as well as in the easiness of handling the reaction mixture after completion of the reaction.