1191-69-1Relevant articles and documents
New lipophilic isoniazid derivatives and their 1,3,4-oxadiazole analogues: Synthesis, antimycobacterial activity and investigation of their mechanism of action
Vosátka, Rudolf,Krátky, Martin,?varcová, Markéta,Janou?ek, Ji?í,Stola?íková, Ji?ina,Madacki, Jan,Huszár, Stanislav,Miku?ová, Katarína,Korduláková, Jana,Trejtnar, Franti?ek,Vin?ová, Jarmila
, p. 824 - 835 (2018)
The development of novel drugs is essential for the treatment of tuberculosis and other mycobacterial infections in future. A series of N-alkyl-2-isonicotinoylhydrazine-1-carboxamides was synthesized from isoniazid (INH) and then cyclized to N-alkyl-5-(pyridin-4-yl)-1,3,4-oxadiazole-2-amines. All derivatives were characterised spectroscopically. The compounds were screened for their in vitro antimycobacterial activity against susceptible and multidrug-resistant Mycobacterium tuberculosis (Mtb.) and nontuberculous mycobacteria (NTM; M. avium, M. kansasii). The most active carboxamides were substituted by a short n-alkyl, their activity was comparable to INH with minimum inhibitory concentrations (MICs) against Mtb. of 0.5–2 μM. Moreover, they are non-toxic for HepG2, and some of them are highly active against INH-resistant NTM (MICs ≥4 μM). Their cyclization to 1,3,4-oxadiazoles did not increase the activity. The experimentally proved mechanism of action of 2-isonicotinoylhydrazine-1-carboxamides consists of the inhibition of enoyl-ACP reductase (InhA) in a way similar to INH, which is blocking the biosynthesis of mycolic acids. N-Dodecyl-5-(pyridin-4-yl)-1,3,4-oxadiazol-2-amine as the most efficacious oxadiazole inhibits growth of both susceptible and drug-resistant Mtb. strains with uniform MIC values of 4–8 μM with no cross-resistance to antitubercular drugs including INH. The mechanism of action is not elucidated but it is different from INH. Obtained results qualify these promising derivatives for further investigation.
Triaminoformate long-carbon-chain organosilane quaternary ammonium salt compound as well as preparation and application thereof
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Paragraph 0037; 0039, (2019/07/04)
The invention relates to a triaminoformate long carbon chain organosilane quaternary ammonium salt compound as well as preparation and an application thereof. The structure of the compound is shown ina general formula (I). The preparation method comprises the following steps: firstly, using long-chain aliphatic amine as a raw material to prepare long-carbon-chain isocyanate in an organic solvent;reacting the long-carbon-chain isocyanate with triethanolamine in an organic solvent, and carrying out recrystallization to obtain a triaminoformate fatty chain intermediate; and reacting the obtained intermediate with haloalkyl trimethoxysilane to obtain an organosilane quaternary ammonium salt compound. The organosilane quaternary ammonium salt compound can be applied to preparation of a hierarchical pore ZSM-5 zeolite molecular sieve. The obtained hierarchical pore channel ZSM-5 zeolite molecular sieve is beneficial to diffusion of macromolecular reactants and products, and has a potentialapplication prospect in macromolecular reaction catalysis.
Discovery of a potent and highly β1 specific proteasome inhibitor from a focused library of urea-containing peptide vinyl sulfones and peptide epoxyketones
Van Der Linden, Wouter A.,Willems, Lianne I.,Shabaneh, Tamer B.,Li, Nan,Ruben, Mark,Florea, Bogdan I.,Van Der Marel, Gijs A.,Kaiser, Markus,Kisselev, Alexei F.,Overkleeft, Herman S.
experimental part, p. 181 - 194 (2012/01/12)
Syringolins, a class of natural products, potently and selectively inhibit the proteasome and show promising antitumour activity. To gain insight in the mode of action of syringolins, the ureido structural element present in syringolins is incorporated in
