166967-59-5Relevant academic research and scientific papers
Identification of inhibitors of UDP-galactopyranose mutaseviacombinatorialin situscreening
Fu, Jian,Fu, Huixiao,Xia, Yufen,N'Go, Inès,Cao, Jun,Pan, Weidong,Vincent, Stéphane P.
, p. 1818 - 1826 (2021/03/14)
Anin situscreening assay for UDP-galactopyranose mutase (UGM, an essential enzyme ofM. tuberculosiscell wall biosynthesis) has been developed to discover novel UGM inhibitors. The approach is based on the amide-forming reaction of an amino acid core with various cinnamic acids, followed by a direct fluorescence polarization assay to identify the best UGM binders without isolation and purification of the screened ligands. This assay allows us to perform one-pot high-throughput synthesis and screening of enzyme inhibitors in a 384-well plate format. UGM ligands were successfully identified by this technology and their inhibition levels were established from pure synthetic compoundsin vitroand in a whole cell antibacterial assay. This study provides a blueprint for designing enamide structures as new UGM inhibitors and anti-mycobacterial agents.
NOVEL AMINOPEPTIDASE INHIBITORS AND METHODS OF USE
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Paragraph 0047, (2017/02/09)
An aminopeptidase inhibitor compound comprising a biaryl, hydroxamic acid based core of formula: wherein X is a 5 or 6-membered ring, and including pharmaceutically acceptable salts and solvates thereof.
SUBSTITUTED PHENYLALANINE DERIVATIVES
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Paragraph 0439; 0440, (2016/10/17)
The invention relates to substituted phenylalanine derivatives and to processes for preparation thereof, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of cardiovascular disorders and/or severe perioperative blood loss.
Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions
Drinkwater, Nyssa,Vinh, Natalie B.,Mistry, Shailesh N.,Bamert, Rebecca S.,Ruggeri, Chiara,Holleran, John P.,Loganathan, Sasdekumar,Paiardini, Alessandro,Charman, Susan A.,Powell, Andrew K.,Avery, Vicky M.,McGowan, Sheena,Scammells, Peter J.
, p. 43 - 64 (2016/01/30)
Malaria remains a global health problem, and though international efforts for treatment and eradication have made some headway, the emergence of drug-resistant parasites threatens this progress. Antimalarial therapeutics acting via novel mechanisms are urgently required. Plasmodium falciparum M1 and M17 are neutral aminopeptidases which are essential for parasite growth and development. Previous work in our group has identified inhibitors capable of dual inhibition of PfA-M1 and PfA-M17, and revealed further regions within the protease S1 pockets that could be exploited in the development of ligands with improved inhibitory activity. Herein, we report the structure-based design and synthesis of novel hydroxamic acid analogues that are capable of potent inhibition of both PfA-M1 and PfA-M17. Furthermore, the developed compounds potently inhibit Pf growth in culture, including the multi-drug resistant strain Dd2. The ongoing development of dual PfA-M1/PfA-M17 inhibitors continues to be an attractive strategy for the design of novel antimalarial therapeutics.
A versatile approach to noncoded β-hydroxy-α-amino esters and α-amino acids/esters from morita-baylis-hillman adducts
Ullah, Hamid,Ferreira, Andr V.,Bendassolli, Jos A.,Rodrigues, Manoel T.,Formiga, Andr Luiz B.,Coelho, Fernando
, p. 113 - 123 (2015/02/02)
A simple and straightforward approach to the diastereoselective synthesis of noncoded β-hydroxy-α-amino esters from Morita-Baylis-Hillman (MBH) adducts is described. The strategy is based on a one-pot sequence involving an oxidative cleavage of the double bond of silylated Morita-Baylis-Hillman adducts, followed by the reaction with hydroxylamine hydrochloride/pyridine to form oximes. The stereoselective reduction of the oximes with the mixture MoCl5·nH2O/NaBH3CN led to the corresponding anti-β-hydroxy-α-amino esters in four steps in good overall yield and with diastereoselectivity higher than 95%. A slight modification of the synthetic approach has allowed for the racemic synthesis of a set of noncoded α-amino esters/acids and DOPA
Fixation and recycling of nitrogen monoxide through carbonitrosation reactions
De Salas, Cristina,Heinrich, Markus R.
, p. 2982 - 2987 (2014/06/10)
The removal of nitrogen monoxide from gas streams through complexation to iron(ii) ions in aqueous dimethylsulfoxide can be combined with a new variant of the Meerwein arylation, which incorporates the previously complexed NO into organic compounds to give oximes as final products. The first step of this two-step process has been evaluated regarding the effectiveness of the NO absorption and the sensitivity of the aqueous iron(ii)-DMSO solution towards oxygen from air, in both cases in comparison with the known BioDeNOx process. The subsequent Meerwein arylation, which was designed with the intention to make use of nitrogen monoxide as the simplest nitrogen-centered radical scavenger, is shown to tolerate an exceptionally broad spectrum of substituents on the aromatic core of the diazonium salts including electron-donating as well as electron-withdrawing substituents. Under simple conditions the resulting oximes can be converted to racemic amino acid esters. This journal is the Partner Organisations 2014.
NOVEL COMPOUNDS FOR MODULATION OF ORPHAN NUCLEAR RECEPTOR RAR-RELATED ORPHAN RECEPTOR-GAMMA (RORγ GAMMA, NR1F3) ACTIVITY AND FOR THE TREATMENT OF CHRONIC INFLAMMATORY AND AUTOIMMUNE DISEASE
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Page/Page column 39, (2011/10/03)
The invention provides modulators for the orphan nuclear receptor RORγ and methods for treating RORγ mediated diseases by administrating these novel RORγ modulators to a human or a mammal in need thereof. Specifically, the present invention provides compounds of Formula (1) and the enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof.
Novel compounds for modulation of orphan nuclear receptor RAR-related orphan receptor-gamma (ROR gamma, NR1F3) activity and for the treatment of chronic inflammatory and autoimmune desease
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Paragraph 0097, (2013/03/26)
The invention provides modulators for the orphan nuclear receptor RORγ and methods for treating RORγ mediated diseases by administrating these novel RORγ modulators to a human or a mammal in need thereof. Specifically, the present invention provides compounds of formula (1) or (2) and the enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof.
4, 6-DISUBSTITUTED 2-AMINO-PYRIMIDINES AS HISTAMINE H4 RECEPTOR MODULATORS
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Page/Page column 128-129, (2010/07/09)
The present invention relates to substituted heterocyclic compounds of Formula (I) or pharmaceutically acceptable salts or N-oxides or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are histamine H4 receptor inhibitors/antagonists useful in the treatment of histamine H4 receptor-associated conditions or diseases or disorders including, for example, inflammatory diseases or disorders, pruritus, and pain.
