115186-33-9

Usage

Uses

Used in Pharmaceutical Industry:
N-Boc-D-phenylalanine N'-Methoxy-N'-MethylaMide is used as a protected intermediate for the synthesis of Darunavir (D193500), a second-generation HIV-1 protease inhibitor. Its role in the synthesis process is crucial, as it helps in the development of this potent antiretroviral drug, which is effective in treating HIV-1 infections and improving the quality of life for patients.
In the synthesis of Darunavir, N-Boc-D-phenylalanine N'-Methoxy-N'-MethylaMide contributes to the formation of the final drug molecule by providing a stable and protected building block. This allows for the efficient assembly of the complex structure of Darunavir, which is essential for its activity as an HIV-1 protease inhibitor. The compound's use in this application highlights its importance in the development of life-saving medications for the treatment of HIV-1.

Upstream product

• 18942-49-9 Boc-D-Phe-OH 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 1117-97-1 N,0-dimethylhydroxylamine 

Downstream Products

• 133657-45-1 (R)-2-Amino-N-methoxy-N-methyl-3-phenyl-propionamide 
• 188771-20-2 (3R)-3-(tert-butyloxycarbonylamino)-1,4-diphenylbutan-2-one 
• 854301-00-1 (Z)-(R)-2-Benzyloxycarbonylamino-4-tert-butoxycarbonylamino-5-phenyl-pent-2-enoic acid methyl ester 
• 911470-88-7 [(1S,3R)-3-(4-Chloro-benzylamino)-4-phenyl-1-(piperidine-1-carbonyl)-butyl]-carbamic acid benzyl ester 
• 482374-26-5 (1-benzyl-2-hydroxy-but-3-enyl)-carbamic acid tert-butyl ester 

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.

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)

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

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.

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.

Binding cooperativity between a ligand carbonyl group and a hydrophobic side chain can be enhanced by additional H-bonds in a distance dependent manner: A case study with thrombin inhibitors

One of the underappreciated non-covalent binding factors, which can significantly affect ligand-protein binding affinity, is the cooperativity between ligand functional groups. Using four different series of thrombin inhibitors, we reveal a strong positiv

Synthesis and biological evaluations of novel endomorphin analogues containing α-hydroxy-β-phenylalanine (AHPBA) displaying mixed μ/δ opioid receptor agonist and δ opioid receptor antagonist activities

A novel series of endomorphin-1 (EM-1) and endomorphin-2 (EM-2) analogues was synthesized, incorporating chiral α-hydroxy-β-phenylalanine (AHPBA), and/or Dmt1-Tic2 at different positions. Pharmacological activity and metabolic stabil

Rational construction of triazole/urea based peptidomimetic macrocycles as pseudocyclo-β-peptides and studies on their chirality controlled self-assembly

A tandem macro-dimerization reaction via a Cu(I) catalyzed azide/alkyne cycloaddition reaction has been employed to construct triazole/urea based peptidomimetic macrocycles considered as pseudocyclo-β-peptides. Introduction of one particular chirality in

Deglycobleomycin A6 analogues modified in the methylvalerate moiety

Previous studies have indicated that the methylvalerate subunit of bleomycin (BLM) plays an important role in facilitating DNA cleavage by BLM and deglycoBLM. Eleven methylvalerate analogues have been synthesized and incorporated into deglycoBLM congeners by the use of solid-phase synthesis. The effect of the valerate moiety in the deglycoBLM analogues has been studied by comparison with the parent deglycoBLM A5 using supercoiled DNA relaxation and sequence-selective DNA cleavage assays. All of the deglycoBLM analogues were found to effect the relaxation of the plasmid DNA. Those analogues having aromatic C4-substituents exhibited cleavage efficiency comparable to that of deglycoBLM A5. Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage.

Synthesis of new (-)-bestatin-based inhibitor libraries reveals a novel binding mode in the S1 pocket of the essential malaria M1 metalloaminopeptidase

The malarial PfA-M1 metallo-aminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-d-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the α-hydroxyβ-amino acid (P1) or the adjacent naturalα-amino acid (P1′). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBzl) 16 at the P1 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PfA-M1 pocket that interacts with the P1 side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.