10418-01-6

Upstream product

• 1080-06-4 L-Tyr-OMe 
• 65-85-0 benzoic acid 
• 3417-91-2 L-tyrosine methyl ester HCl 
• 60-18-4 L-tyrosine 
• 98-88-4 benzoyl chloride 
• 67-56-1 methanol 
• 24486-16-6 4-(4-hydroxybenzyl)-2-phenyloxazol-5(4H)-one 

Downstream Products

• 67-56-1 methanol 
• 2566-23-6 N-benzoyl-L-tyrosine 
• 934221-09-7 N-(N-benzoyl-L-tyrosyl)-L-phenylalaninol 

Relevant academic research and scientific papers

Process development of clinical anti-HBV drug Y101: Identification and synthesis of novel impurities

Nine novel process impurities of N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol (Y101) observed during the laboratory optimization and later during its bulk synthesis are described in this article. The impurities were monitored by HPLC,

Discovery of Modified Amidate (ProTide) Prodrugs of Tenofovir with Enhanced Antiviral Properties

This study describes the discovery of novel prodrugs bearing tyrosine derivatives instead of the phenol moiety present in FDA-approved tenofovir alafenamide fumarate (TAF). The synthesis was optimized to afford diastereomeric mixtures of novel prodrugs in

Design, synthesis and evaluation of novel phenyl propionamide derivatives as non-nucleoside hepatitis B virus inhibitors

As an ongoing search for potent non-nucleoside anti-HBV agents with novel structures, we described a series of phenyl propionamide derivatives (3a-b, 4a-e, 7a-g, 8a-h and 9a-b) by pharmacophore fusion strategy in the present work. All the compounds exhibited an anti-HBV activity to some extent. Among them, compounds 8d and 9b displayed most potent anti-HBV activity with IC50 values on HBV DNA replication of 0.46 and 0.14 μM, respectively. And the selective index values of 8d and 9b were more than 217.39 and 153.14, suggesting that 8d and 9b exhibited favorable safety profiles. Interestingly, 8d and 9b possessed significantly antiviral activities against lamivudine and entecavir resistant HBV mutants with IC50 values of 0.77 and 0.32 μM. Notably, preliminary anti-HBV action mechanism studies showed that 8d could inhibit intracellular HBV pgRNA and RT activity of the HBV polymerase. Molecular docking studies suggested that compound 8d could fit into the dimer-dimer interface of HBV core protein by hydrophobic interaction. In addition, in silico prediction of physicochemical properties showed that 8d conformed well to the Lipinski's rule of five, suggesting its potential for use as a drug like molecule. Taken together, 8d possessed significantly anti-HBV activity, low toxicity, diverse anti-HBV mechanism and favorable physicochemical properties, and warranted further investigation as a promising non-nucleoside anti-HBV candidate.

Synthesis and Biological Evaluation of Matijin-Su Derivatives as Potential Antihepatitis B Virus and Anticancer Agents

A series of Matijin-Su (MTS, (2S)-2-{[(2S)-2-benzamido-3-phenylpropanoyl]amino}-3-phenylpropyl acetate) derivatives were synthesized and evaluated for their anti-HBV and cytotoxic activities in?vitro. Six compounds (4g, 4j, 5c, 5g, 5h and 5i) showed signi

Synthesis and anti-tumor activity evaluation of Matijin-Su derivatives

A series of Matijin-Su (MTS, N-(N-benzoyl-l-phenylalanyl)-O-acetyl-l- phenylalanol) derivatives was synthesized and evaluated for their anti-tumor activities in hepatocellular carcinoma cells. The IC50 of compounds 1, 3, 4, 11, 13 were less than 20 μM, and compound 1 and 3 showed an IC 50 value of less than 9 μM. Expansion inhibition could be found significantly in compound 1 and 3-treated human hepatoma cell HepG2 and PLC/PRF/5, while both compounds exhibit lower toxicity to human hepatocyte cell line L-02. Compound 1 and 3 could induce cell cycle arrest at G1/S phase. This may be attributed to increase level of intracellular reactive oxygen species (ROS). Up-regulation of p38 MAPK activity in responding the ROS stabilize p53 and activate p21 transcription, the critical regulatory in G1/S checkpoint. Observations in this study shed light on the potential of MTS derivatives compound 1 and 3 as novel suppressors to human liver cancer.

Synthesis and biological evaluation of Matijing-Su derivatives as potent anti-HBV agents

A series of Matijing-Su (MTS, N-(N-benzoyl-l-phenylalanyl)-O-acetyl-l- phenylalanol) derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity in 2.2.15 cells. The IC50 of compounds 14a (0.71 μM), 13c (2.85 μM), 13b (4.37 μM), etc. and the selective index of 13g (161.01), 13c (90.45), 13a (85.09) etc. of the inhibition on the replication of HBV DNA were better than those of the positive control lamivudine (IC50: 82.42 μM, SI: 41.59). Compounds 13o, 13p, and 16a also exhibited significant anti-HBV activity.

Chemical approaches to protein engineering 20: The transformation of coded amino acid tyrosine to pro-templates having metal uptake potential in peptide/protein segments

From vantage of inorganic chemistry, the inability of any of the coded amino acid side chains to carry metal ions should appear as a grave omission in the genetic code, particularly since, metallo-enzymes play a pivotal role in diverse facets of life processes. The ready transformation of the coded amino acid tyrosine to metal uptake systems forms the core of the present work. 3-Acetyl-tyrosine [Tyr(3-Ac)]- readily derived from tyrosine is amenable to normal protocols in peptide synthesis and offers ideal ligand dispositions to craft protemplates. This aspect has been illustrated by three broad strategies. The reaction of Tyr(3-Ac) with AEH, the mono Schiff base of acetylacetone and ethylenediamine (EDA), yields the protemplates II [TYr(3-Ac)-AEH] which can also be conveniently assembled, in situ, from acetylacetone, EDA and Tyr(3-Ac). Tripeptide, where Tyr(3-Ac) is flanked by Ala and Ser has been prepared and protemplate formation demonstrated in a peptide environment. Thus, either by normal peptide synthesis or by insertion of peptides containing Tyr(3-Ac), active sites for metal uptake can be constructed, thereby, in principle, obviating the need for 50-70 residues normally required. Protemplates for metal uptake can be readily crafted by cross linking of Tyr(3-Ac) with EDA. This has also been illustrated with Ala-Tyr(3-Ac)-Ser-OMe. Thus, peptides where Tyr(3-Ac) is placed at appropriate locations, with EDA, can provide conformationally restrained metal uptake systems. Conversely, the oxime of Tyr(3-Ac) as well as the Schiff bases with β-ethanolamine and Gly-OMe can bring together proximate residues by metal complexation. This aspect has been experimentally realized. The protemplates from Tyr(3-Ac) [Schiff bases with AEH / EDA / β-ethanolamine / Gly-OMe / and oximes] readily take up Cu(II), Co(II), and Ni(II) to form stable, well defined templates. The EPR spectra of the Cu(II) templates are that for typical square planar complexes, although in few sterically crowded examples rhombohedral distortion was seen. The observed A and g parameters compared favorably with that reported for metalloproteins, with particular closeness to laccase. Cyclic voltammetric studies were complicated by incursion of ligand oxidation, although in two cases clear E° values of 340 mV and 305 mV were obtained, which lie in the range reported for metallo-proteins. The Ni(II) templates exhibited the expected 1H NMR profile; in one example, coordination with two water molecules was seen. The Co(II) templates exhibited typical d-d transition at ～600 nm in the visible spectrum.

Design and synthesis of amidino-tyrosine derivatives as non-peptide fibrinogen receptor antagonists

The design, synthesis and antiaggregation activity of amidino-tyrosine derivatives based on Arg-Gly-Asp (RGD) tripepride sequence as non-peptide fibrinogen receptor antagonists is described. Optimization of the spacer and the substituent at the C-terminal is reported.

Enzymatic Asymmetric Synthesis of α-Amino Acids. Enantioselective Cleavage of 4-Substituted Oxazolin-5-ones and Thiazolin-5-ones

A general enzymatic asymmetric synthesis of L-α-amino acids has been developed.This method entails the use of the Pseudomonas cepacia lipase (P-30) to catalyze the enantioselective methanolysis of a variety of 4-substituted 2-phenyloxazolin-5-one derivatives in a nonpolar organic solvent to furnish optically active N-benzoyl-L-α-amino acid methyl esters (ee = 66-98 percent), which in turn is subjected to a protease-catalyzed kinetic resolution yielding enantiomerically pure N-benzoyl-L-α-amino acids.This synergistic coupling of two enzymes allows the ready preparation of L-α-amino acids of high enantiopurity in yields greater than 50 percent, an inherent advantage over conventional resolution procedures.Two proteases were found to catalyze the enantioselective hydrolysis of a variety of 4-substituted 2-phenylthiazolin-5-one derivatives to give N-(thiobenzoyl)-L-α-amino acids of high optical purity.

FACILE CHEMICAL SYTHESIS OF S,S-ISODITYROSINE, A NATURALLY-OCCURRING CROSS-LINKING AMINO ACID

Ullmann coupling of the two protected S-tyrosine derivatives 6 and 9 afforded the protected isodityrosine 10 which was converted into the natural bis-amino acid S,S-isodityrosine 1 in good yield.