59190-99-7

Upstream product

• 56-41-7 L-alanin 
• 617-09-4 di-o-tolyl carbonate 
• 16480-55-0 sodium L-alaninate 
• 79-22-1 methyl chloroformate 
• 1437-22-5 p-nitrophenyl N-methoxycarbonyl-L-phenylalaninate 

Downstream Products

• 59190-97-5 Aethyl-Moc-L-Ala-p-aminobenzoat 
• 77447-97-3 (S)-2-<(Methoxycarbonyl)amino>-1-phenylpropanone 
• 77357-62-1 (R)-2-<(Methoxycarbonyl)amino>-1-phenylpropanone 
• 1512624-50-8 C₃₂H₄₀N₆O₈ 
• 1310695-63-6 methyl {(2S)-1-[(2S)-2-{5-[4’-(2-{(2S)-1-[N-(methoxycarbonyl)-L-alanyl]pyrrolidin-2-yl}-1,3-thiazol-5-yl)biphenyl-4-yl]-1,3-thiazol-2-yl}pyrrolidin-1-yl]-1-oxopropan-2-yl}carbamate 
• 1242088-46-5 C₃₈H₄₄N₈O₆ 
• 1228668-06-1 C₃₆H₄₈N₈O₆ 

Relevant academic research and scientific papers

Structural Analysis of Potent Hybrid HIV-1 Protease Inhibitors Containing Bis-tetrahydrofuran in a Pseudosymmetric Dipeptide Isostere

The design, synthesis, and X-ray structural analysis of hybrid HIV-1 protease inhibitors (PIs) containing bis-tetrahydrofuran (bis-THF) in a pseudo-C2-symmetric dipeptide isostere are described. A series of PIs were synthesized by incorporating bis-THF of darunavir on either side of the Phe-Phe isostere of lopinavir in combination with hydrophobic amino acids on the opposite P2/P2′ position. Structure-activity relationship studies indicated that the bis-THF moiety can be attached at either the P2 or P2′ position without significantly affecting potency. However, the group on the opposite P2/P2′ position had a dramatic effect on potency depending on the size and shape of the side chain. Cocrystal structures of inhibitors with wild-type HIV-1 protease revealed that the bis-THF moiety retained similar interactions as observed in the darunavir-protease complex regardless of the position on the Phe-Phe isostere. Analyses of cocrystal structures and molecular dynamics simulations provide insights into optimizing HIV-1 PIs containing bis-THF in non-sulfonamide dipeptide isosteres.

A novel, potent, and orally bioavailable thiazole HCV NS5A inhibitor for the treatment of hepatitis C virus

A medicinal chemistry program based on the small-molecule HCV NS5A inhibitor daclatasvir has led to the discovery of dimeric phenylthiazole compound 8, a novel and potent HCV NS5A inhibitor. The subsequent SAR studies and optimization revealed that the cycloalkyl amide derivatives 27a-29a exhibited superior potency against GT1b with GT1b EC50 values at picomolar concentration. Interestingly, high diastereospecificity for HCV inhibition was observed in this class with the (1R,2S,1′R,2′S) diastereomer displaying the highest GT1b inhibitory activity. The best inhibitor 27a was found to be 3-fold more potent (GT1b EC50 = 0.003 nM) than daclatasvir (GT1b EC50 = 0.009 nM) against GT1b, and no detectable in vitro cytotoxicity was observed (CC50 > 50 μM). Pharmacokinetic studies demonstrated that compound 27a had an excellent pharmacokinetic profiles with a superior oral exposure and desired bioavailability after oral administration in both rats and dogs, and therefore it was selected as a developmental candidate for the treatment of HCV infection.

HEPATITIS C VIRUS INHIBITORS

The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

Thermodynamic and Structural Investigation of Synthetic Actinide-Peptide Scaffolds

The complexation of uranium and europium, in oxidation states +VI and +III, respectively, was investigated with pertinent bio-inorganic systems. Three aspartate-rich pentapeptides with different structural properties were selected for study to rationalize the structure-affinity relationships. Thermodynamic results, crosschecked by both isothermal titration calorimetry and time-resolved laser fluorescence spectroscopy, showed different affinity depending on the peptide for both Eu(III) and U(VI). The thermodynamic aspects were correlated to structural predictions, which were acquired by density functional theory quantum chemical calculations and from IR and extended X-ray absorption fine structure experiments. The combination of these microscopic properties revealed that carbonyl-metal interactions affected the entropy in the case of europium, while the larger uranyl cation was mostly affected by preorganization and steric effects, so that the affinity was enhanced through enthalpy. The approach described here revealed various microscopic aspects governing peptide actinide affinity. Highlighting these mechanisms should certainly contribute to the rational synthesis of higher affinity biomimetic aspartic ligands.

Matched and mixed cap derivatives in the tetracyclic indole class of HCV NS5A inhibitors

A matched and mixed capping SAR study was conducted on the tetracyclic indole class of HCV NS5A inhibitors to examine the influence of modifications of this region on the overall HCV virologic resistance profiles.

BENZIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING BENZIDINE DERIVATIVE FOR TREATING LIVER DISEASE CAUSED BY HEPATITIS C VIRUS

The disclosed compounds have antiviral activity against C-type virus, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient for preventing or treating liver disease caused by hepatitis C virus. The benzidine derivative according to the present invention has excellent antiviral activity against hepatitis C virus and exhibits excellent medicinal activity in the living body, and thus the pharmaceutical composition containing the same as an active ingredient can be useful as a pharmaceutical composition for preventing or treating liver disease, such as acute hepatitis C, chronic hepatitis C, cirrhosis, or hepatocellular carcinoma, caused by C-type virus.

FUSED TRICYCLIC SILYL COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES

no abstract published

Potent hepatitis C virus NS5A inhibitors containing a benzidine core

Here we report the discovery of a series of potent hepatitis C virus (HCV) NS5A inhibitors based on the benzidine prolinamide backbone. Taking a simple synthetic route, we developed a novel inhibitor structure, which allows easy modification, and through optimization of the capping group, we identified compound 6 with highly potent anti-HCV activity. Compound 6 is nontoxic and is anticipated to be an effective HCV drug candidate.

HEPATITIS C VIRUS INHIBITORS

The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

HEPATITIS C INHIBITOR COMPOUNDS

Compounds of Formula (I) and (II) wherein R1, R2, R3, R6, A and A' are defined herein. The compounds are useful as inhibitors of the function of NS5A protein encoded by HCV for the treatment of hepatitis C viral infection.