170112-07-9

Basic information

• Product Name: Carbamic acid, [(1S)-1-formyl-3-phenylpropyl]-, 1,1-dimethylethyl ester
• Synonyms: (S)-tert-butyl (1-formyl-3-phenylpropyl)carbamate;tert-butyl (S)-1-formyl-3-phenylpropylcarbamate;Carbamic acid,[(1S)-1-formyl-3-phenylpropyl]-,1,1-dimethylethyl ester;(2S)-2-tert-Butoxycarbonylamino-4-phenylbutanal;N-(tert-butoxycarbonyl)-L-homophenylalaninal;N-Boc-L-homophenylalanal;N-tert-butoxycarbonyl-homophenylalanal
• CAS NO: 170112-07-9
• Molecular Formula: C15H21NO3
• Molecular Weight: 263.337
• Mol File: 170112-07-9.mol

Chemical Properties

• CAS DataBase Reference: Carbamic acid, [(1S)-1-formyl-3-phenylpropyl]-, 1,1-dimethylethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: Carbamic acid, [(1S)-1-formyl-3-phenylpropyl]-, 1,1-dimethylethyl ester(170112-07-9)
• EPA Substance Registry System: Carbamic acid, [(1S)-1-formyl-3-phenylpropyl]-, 1,1-dimethylethyl ester(170112-07-9)

Safety Data

• Hazardous Substances Data: 170112-07-9(Hazardous Substances Data)

Upstream product

• 183444-03-3 tert-butyl (S)-(1-(methoxy(methyl)amino)-1-oxo-4-phenylbutan-2-yl)-carbamate 
• 116611-54-2 (1S-hydroxymethyl-3-phenylpropyl)carbamic acid tert-butyl ester 
• 82732-07-8 Boc-L-homophenylalanine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 943-73-7 D-homophenylalanine 

Downstream Products

• 294885-24-8 (2RS,3S)-3-(tert-Butoxycarbonyl)amino-2-hydroxy-5-phenylpentanenitrile 
• 294885-19-1 2S-amino-1-oxazol-2-yl-4-phenylbutan-1-ol trifluoroacetic acid salt 
• 294885-20-4 tert-butyl 2-hydroxy-2-oxazol-2-yl-1S-phenethylethylcarbamate 
• 1354894-16-8 N-((S)-1-oxo-3-phenyl-1-(((S,E)-5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)amino)propan-2-yl)-4-(prop-2-yn-1-yl)piperazine-1-carboxamide 
• 1354894-27-1 (S,E)-5-phenyl-1-((4-(prop-2-yn-1-yloxy)phenyl)sulfonyl)pent-1-en-3-amine trifluoroacetate 
• 1354894-17-9 4-ethynylbenzyl((S)-1-oxo-3-phenyl-1-(((S,E)-5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)amino)propan-2-yl)carbamate 
• 1354894-18-0 N-((S)-1-oxo-3-phenyl-1-(((S,E)-5-phenyl-1-((4-(prop-2-yn-1-yloxy)phenyl)sulfonyl)pent-1-en-3-yl)amino)propan-2-yl)morpholine-4-carboxamide 
• 233277-99-1 4-Methyl-piperazine-1-carboxylic acid [(S)-1-((E)-(S)-3-benzenesulfonyl-1-phenethyl-allylcarbamoyl)-2-phenyl-ethyl]-amide 
• 862388-09-8 (3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-5-phenylpentanoic acid 

Relevant articles and documents

Fluorovinylsulfones and -Sulfonates as Potent Covalent Reversible Inhibitors of the Trypanosomal Cysteine Protease Rhodesain: Structure-Activity Relationship, Inhibition Mechanism, Metabolism, and in Vivo Studies

Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, a pathogen causing Human African Trypanosomiasis, and a validated drug target. Recently, we reported the development of α-halovinylsulfones as a new class of covalent reversible cysteine protease inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, the most potent and selective inhibitor in the series, shows a single-digit nanomolar affinity and high selectivity toward mammalian cathepsins B and L. Enzymatic dilution assays and MS experiments indicate that 2d is a slow-tight binder (Ki = 3 nM). Furthermore, the nonfluorinated 2d-(H) shows favorable metabolism and biodistribution by accumulation in mice brain tissue after intraperitoneal and oral administration. The highest antitrypanosomal activity was observed for inhibitors with an N-terminal 2,3-dihydrobenzo[b][1,4]dioxine group and a 4-Me-Phe residue in P2 (2e/4e) with nanomolar EC50 values (0.14/0.80 μM). The different mechanisms of reversible and irreversible inhibitors were explained using QM/MM calculations and MD simulations.

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.

Vinyl sulfone-based inhibitors of trypanosomal cysteine protease rhodesain with improved antitrypanosomal activities

The number of reported cases of Human African Trypanosmiasis (HAT), caused by kinetoplastid protozoan parasite Trypanosoma brucei, is declining in sub-Saharan Africa. Historically, such declines are generally followed by periods of higher incidence, and one of the lingering public health challenges of HAT is that its drug development pipeline is historically sparse. As a continuation of our work on new antitrypanosomal agents, we found that partially saturated quinoline-based vinyl sulfone compounds selectively inhibit the growth of T. brucei but displayed relatively weak inhibitory activity towards T. brucei's cysteine protease rhodesain. While two nitroaromatic analogues of the quinoline-based vinyl sulfone compounds displayed potent inhibition of T. brucei and rhodesain. The quinoline derivatives and the nitroaromatic-based compounds discovered in this work can serve as leads for ADME-based optimization and pre-clinical investigations.

Peptidomimetic Vinyl Heterocyclic Inhibitors of Cruzain Effect Antitrypanosomal Activity

Cruzain, an essential cysteine protease of the parasitic protozoan, Trypanosoma cruzi, is an important drug target for Chagas disease. We describe here a new series of reversible but time-dependent inhibitors of cruzain, composed of a dipeptide scaffold appended to vinyl heterocycles meant to provide replacements for the irreversible reactive "warheads" of vinyl sulfone inactivators of cruzain. Peptidomimetic vinyl heterocyclic inhibitors (PVHIs) containing Cbz-Phe-Phe/homoPhe scaffolds with vinyl-2-pyrimidine, vinyl-2-pyridine, and vinyl-2-(N-methyl)-pyridine groups conferred reversible, time-dependent inhibition of cruzain (Ki? = 0.1-0.4 μM). These cruzain inhibitors exhibited moderate to excellent selectivity versus human cathepsins B, L, and S and showed no apparent toxicity to human cells but were effective in cell cultures of Trypanosoma brucei brucei (EC50 = 1-15 μM) and eliminated T. cruzi in infected murine cardiomyoblasts (EC50 = 5-8 μM). PVHIs represent a new class of cruzain inhibitors that could progress to viable candidate compounds to treat Chagas disease and human sleeping sickness.

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Quantum Chemical-Based Protocol for the Rational Design of Covalent Inhibitors

We propose a structure-based protocol for the development of customized covalent inhibitors. Starting from a known inhibitor, in the first and second steps appropriate substituents of the warhead are selected on the basis of quantum mechanical (QM) computations and hybrid approaches combining QM with molecular mechanics (QM/MM). In the third step the recognition unit is optimized using docking approaches for the noncovalent complex. These predictions are finally verified by QM/MM or molecular dynamic simulations. The applicability of our approach is successfully demonstrated by the design of reversible covalent vinylsulfone-based inhibitors for rhodesain. The examples show that our approach is sufficiently accurate to identify compounds with the desired properties but also to exclude nonpromising ones.

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Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: Design, synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibition

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