103127-52-2Relevant articles and documents
Solid phase synthesis of olefin and hydroxyethylene peptidomimetics
Rotella, David P.
, p. 12246 - 12247 (1996)
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Improved synthesis of chiral N-protected allylic amines
Wei,Knaus
, p. 1463 - 1466 (1994)
The α-ester group of N-protected α-amino esters was reduced with diisobutylaluminum hydride to an intermediate aluminoxy acetal that on reaction with a Wittig reagent afforded the title chiral compounds in 48-78% chemical yields.
Design and synthesis of novel phe-phe hydroxyethylene derivatives as potential coronavirus main protease inhibitors
Khorsandi, Zahra,Afshinpour, Maral,Molaei, Fatemeh,Askandar, Rafee Habib,Keshavarzipour, Fariba,Abbasi, Maryam,Sadeghi-Aliabadi, Hojjat
, (2021)
In response to the current pandemic caused by the novel SARS-CoV-2, we design new compounds based on Lopinavir structure as an FDA-approved antiviral agent which is currently under more evaluation in clinical trials for COVID-19 patients. This is the first example of the preparation of Lopinavir isosteres from the main core of Lopinavir conducted to various heterocyclic fragments. It is proposed that main protease inhibitors play an important role in the cycle life of coronavirus. Thus, the protease inhibition effect of synthesized compounds was studied by molecular docking method. All of these 10 molecules, showing a good docking score compared. Molecular dynamics (MD) simulations also confirmed the stability of the best-designed compound in Mpro active site. Communicated by Ramaswamy H. Sarma.
Peptidomimetic plasmepsin inhibitors with potent anti-malarial activity and selectivity against cathepsin D
Zogota, Rimants,Kinena, Linda,Withers-Martinez, Chrislaine,Blackman, Michael J.,Bobrovs, Raitis,Pantelejevs, Teodors,Kanepe-Lapsa, Iveta,Ozola, Vita,Jaudzems, Kristaps,Suna, Edgars,Jirgensons, Aigars
supporting information, p. 344 - 352 (2018/12/11)
Following up the open initiative of anti-malarial drug discovery, a GlaxoSmithKline (GSK) phenotypic screening hit was developed to generate hydroxyethylamine based plasmepsin (Plm) inhibitors exhibiting growth inhibition of the malaria parasite Plasmodium falciparum at nanomolar concentrations. Lead optimization studies were performed with the aim of improving Plm inhibition selectivity versus the related human aspartic protease cathepsin D (Cat D). Optimization studies were performed using Plm IV as a readily accessible model protein, the inhibition of which correlates with anti-malarial activity. Guided by sequence alignment of Plms and Cat D, selectivity-inducing structural motifs were modified in the S3 and S4 sub-pocket occupying substituents of the hydroxyethylamine inhibitors. This resulted in potent anti-malarials with an up to 50-fold Plm IV/Cat D selectivity factor. More detailed investigation of the mechanism of action of the selected compounds revealed that they inhibit maturation of the P. falciparum subtilisin-like protease SUB1, and also inhibit parasite egress from erythrocytes. Our results indicate that the anti-malarial activity of the compounds is linked to inhibition of the SUB1 maturase plasmepsin subtype Plm X.
Fluorocyclisation via I(I)/I(III) catalysis: A concise route to fluorinated oxazolines
Daniliuc, Constantin G.,Gilmour, Ryan,Kehr, Gerald,Meyer, Stephanie,Scheidt, Felix,Thiehoff, Christian,Yilmaz, Gülay
supporting information, p. 1021 - 1027 (2020/05/06)
Herein, we describe a catalytic fluorooxygenation of readily accessible N-allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor, whilst HF serves as both a fluoride source and Br?nsted acid activator. The C(sp3)–F bond of the mono-fluoromethyl unit and the C(sp3)–O bond of the ring are aligned in a synclinal relationship thereby engaging in stabilising hyperconjugative interactions with vicinal, electron-rich σ-bonds (σC–C→σ*C–F and σC–H→σ*C–O). This manifestation of the stereoelectronic gauche effect was established by X-ray crystallographic analysis of a representative example. Given the importance of fluorine in drug discovery, its ability to modulate conformation, and the prevalence of the 2-oxazoline scaffold in Nature, this strategy provides a rapid entry into an important bioisostere class.
