77119-85-8

Usage

Chemical Properties

White or tan crystalline powder

Upstream product

• 87694-53-9 Boc-Phe-OH N,O-dimethyl hydroxamate 
• 19901-50-9 methyl (2R)-2-(t-butoxycarbonylamino)-3-phenylpropionate 
• 115186-33-9 (R)-tert-butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate 
• 106454-69-7 N-tert-butoxycarbonyl-D-Phenylalaninol 
• 144775-04-2 Boc-(R)-dolaphenine 
• 18942-49-9 Boc-D-Phe-OH 
• 24424-99-5 di-tert-butyl dicarbonate 
• 1117-97-1 N,0-dimethylhydroxylamine 
• 3744-87-4 Boc-(R)-Ala 
• 79069-13-9 (R)-2-tertbutoxycarbonylamino-1-propanol 
• 673-06-3 D-(R)-phenylalanine 
• 179077-79-3 ((R)-2-Phenyl-1-thiazol-2-yl-ethyl)-[(1R,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-(2E)-ylidene]-amine 
• 179238-80-3 (1S,2S,5S)-2,6,6-Trimethyl-3-[(E)-(R)-2-phenyl-1-thiazol-2-yl-ethylimino]-bicyclo[3.1.1]heptan-2-ol 
• 144774-97-0 [R-(-)-2-phenyl-1-(2-thiazolyl)ethylamine] 

Downstream Products

• 210427-84-2 (E)-(R)-3-tert-Butoxycarbonylamino-4-phenyl-but-1-ene-1-sulfonic acid methyl ester 
• 117088-23-0 (S)-2-((R)-2-Amino-3-phenyl-propylamino)-4-methyl-pentanoic acid amide 
• 117088-24-1 L-Pheψ-Leu-NH2 
• 199926-83-5 ethyl (R)-(+)-6-(N-tert-butoxycarbonyl)amino-3-ethoxy-7-phenylhepta-2,4-dienoate 
• 482374-27-6 (1-benzyl-2-hydroxy-3-methyl-but-3-enyl)-carbamic acid tert-butyl ester 
• 854301-00-1 (Z)-(R)-2-Benzyloxycarbonylamino-4-tert-butoxycarbonylamino-5-phenyl-pent-2-enoic acid methyl ester 
• 944835-76-1 C₄₀H₆₂N₂O₁₁ 

Relevant academic research and scientific papers

Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L

Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is a promising drug target for novel antivirals against SARS-CoV-2. The marine natural product gallinamide A and several synthetic analogues were identified as potent inhibitors of cathepsin L with IC50 values in the picomolar range. Lead molecules possessed selectivity over other cathepsins and alternative host proteases involved in viral entry. Gallinamide A directly interacted with cathepsin L in cells and, together with two lead analogues, potently inhibited SARS-CoV-2 infection in vitro, with EC50 values in the nanomolar range. Reduced antiviral activity was observed in cells overexpressing transmembrane protease, serine 2 (TMPRSS2); however, a synergistic improvement in antiviral activity was achieved when combined with a TMPRSS2 inhibitor. These data highlight the potential of cathepsin L as a COVID-19 drug target as well as the likely need to inhibit multiple routes of viral entry to achieve efficacy.

Synthesis of α-Ketoamide-Based Stereoselective Calpain-1 Inhibitors as Neuroprotective Agents

Calpain inhibitors have been proposed as drug candidates for neurodegenerative disorders, with ABT-957 entering clinical trials for Alzheimer's disease and mild cognitive impairment. The structure of ABT-957 was very recently disclosed, and trials were te

Pyridone [1, 2-b] [1,5] triazepine derivatives as well as preparation and application thereof (by machine translation)

The invention discloses a hydroxypyridone [1, a-b] [1,5] triazepine derivatives as well as preparation and application thereof. Experiments prove that the hydroxypyridinone [1, 2-b] [1,triazepine derivatives (general formula I) have a good inhibition effect on the RNA polymerase activity of influenza A virus RNA, and can be used as an influenza virus RNA polymerase inhibitor to treat influenza caused by influenza virus. General Formula I is as follows. (by machine translation)

Design of Gallinamide A Analogs as Potent Inhibitors of the Cysteine Proteases Human Cathepsin L and Trypanosoma cruzi Cruzain

Gallinamide A, originally isolated with a modest antimalarial activity, was subsequently reisolated and characterized as a potent, selective, and irreversible inhibitor of the human cysteine protease cathepsin L. Molecular docking identified potential modifications to improve binding, which were synthesized as a suite of analogs. Resultingly, this current study produced the most potent gallinamide analog yet tested against cathepsin L (10, Ki = 0.0937 ± 0.01 nM and kinact/Ki = 8 730 000). From a protein structure and substrate preference perspective, cruzain, an essential Trypanosoma cruzi cysteine protease, is highly homologous. Our investigations revealed that gallinamide and its analogs potently inhibit cruzain and are exquisitely toxic toward T. cruzi in the intracellular amastigote stage. The most active compound, 5, had an IC50 = 5.1 ± 1.4 nM, but was relatively inactive to both the epimastigote (insect stage) and the host cell, and thus represents a new candidate for the treatment of Chagas disease.

A practical diastereoselective synthesis of (?)-bestatin

Diastereoselective addition of nitromethane to Boc-D-Phe-H in the presence of sodium hydride in diethyl ether/hexane containing 15-crown-5 and subsequent N,O-protection with 2,2-dimethoxypropane gave trans-oxazolidine in a diastereomeric ratio of >16:1. T

Synthesis of Enantiomerically Pure 3-Substituted Piperazine-2-acetic Acid Esters as Intermediates for Library Production

The piperazine heterocycle is broadly exploited in FDA-approved drugs and biologically active compounds, but its chemical diversity is usually limited to ring nitrogen substitutions, leaving the four carbon atoms underutilized. Using an efficient six-step synthesis, chiral amino acids were transformed into 3-substituted piperazine-2-acetic acid esters as diastereomeric mixtures whose cis and trans products (dr 0.56 a? 2.2:1, respectively) could be chromatographically separated. From five amino acids (both antipodes) was obtained a complete matrix of 20 monoprotected chiral 2,3-disubstituted piperazines, each as a single absolute stereoisomer, all but one in multigram quantities. In keeping with our overall purpose of constructing more Csp3-enriched compound libraries for drug discovery, these diverse and versatile piperazines can be functionalized on either nitrogen atom, allowing them to be used as scaffolds for parallel library synthesis and as intermediates for the production of novel piperazine compounds.

Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding

Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2-AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4-substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5-position of the piperidine ring provided ultrapotent inhibitor 38 (DH376) with picomolar activity. Compound 38 temporarily reduces fasting-induced refeeding of mice, thereby emulating the effect of cannabinoid CB1-receptor inverse agonists. This was mirrored by 39 (DO34) but also by the negative control compound 40 (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple molecular targets.

As cell necrosis inhibitors of the indole compounds (by machine translation)

The invention relates to chemical formula (1) indole compounds, or its pharmaceutically acceptable salt or isomer, and in containing the same as the characteristic, as an active ingredient for the prevention or treatment of cell necrosis and its associated disease composition and method of manufacturing. (by machine translation)

INDOLE COMPOUND AS INHIBITOR OF NECROSIS

The present invention relates to an indole compound represented by formula (1), a pharmaceutically acceptable salt or isomer thereof, a composition for prevention or treatment of necrosis and necrosis-associated diseases, and a method for preparing the composition, the composition comprising the indole compound or the pharmaceutically acceptable salt or isomer thereof as an active ingredient.

Highly enantioselective hydrogenation of α-oxy functionalized α,β-unsaturated acids catalyzed by a ChenPhos-Rh complex in CF3CH2OH

Rhodium complexes coordinated by Chenphos are very effective catalysts for the enantioselective hydrogenation of α-aryloxy- and α-alkoxy-substituted α,β-unsaturated carboxylic acids under mild conditions in CF3CH2OH. The catalytic system could be successfully employed in building the core structure of a new FDA approved drug LCZ 696.