29053-23-4Relevant articles and documents
Cascade reactions of nitrogen-substituted isocyanates: A new tool in heterocyclic chemistry
Vincent-Rocan, Jean-Fran?ois,Ivanovich, Ryan A.,Clavette, Christian,Leckett, Kyle,Bejjani, Julien,Beauchemin, André M.
, p. 315 - 328 (2015/12/26)
In contrast to normal C-substituted isocyanates, nitrogen-substituted isocyanates (N-isocyanates) are rare. Their high reactivity and amphoteric/ambident nature has prevented the scientific community from exploiting their synthetic potential. Recently, we have developed an in situ formation approach using a reversible equilibrium, which allows controlled generation and reactivity of N-isocyanates and prevents the dimerization that is typically observed with these intermediates. This blocked (masked) N-isocyanate approach enables the use of various N-isocyanate precursors to assemble heterocycles possessing the N-N-CO motif, which is often found in agrochemicals and pharmaceuticals. Cascade reactions for the rapid assembly of several valuable 5- and 6-membered heterocycles are reported, including amino-hydantoins, acyl-pyrazoles, acyl-phthalazinones and azauracils. Over 100 different compounds were synthesized using amino-, imino- and amido-substituted N-isocyanates, demonstrating their potential as powerful intermediates in heterocyclic synthesis. Their reactivity also enables access to unprecedented bicyclic derivatives and to substitution patterns of azauracils that are difficult to access using known methods, illustrating that controlled reactivity of N-isocyanates provides new disconnections, and a new tool to assemble complex N-N-CO containing motifs.
Facile one-pot synthesis of 4-substituted semicarbazides
Bogolubsky, Andrey V.,Moroz, Yurii S.,Mykhailiuk, Pavel K.,Dmytriv, Yurii V.,Pipko, Sergey E.,Babichenko, Liudmyla N.,Konovets, Anzhelika I.,Tolmachev, Andrey
, p. 1063 - 1069 (2015/02/18)
A diverse library of twenty-five 4-mono- and disubstituted semicarbazides was prepared in a one-pot two-step approach. The method includes formation of a carbamate from bis(2,2,2-trifluoroethyl)carbonate or 2,2,2-trifluoroethylchloroformate and a primary or secondary amine and subsequent interaction of the carbamate with hydrazine to result in a semicarbazide. The approach allowed to obtain 4-substituted semicarbazides on a large scale in good yield and high purity. This journal is
Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?
Adkison, Kim K.,Barrett, David G.,Deaton, David N.,Gampe, Robert T.,Hassell, Anne M.,Long, Stacey T.,McFadyen, Robert B.,Miller, Aaron B.,Miller, Larry R.,Payne, J. Alan,Shewchuk, Lisa M.,Wells-Knecht, Kevin J.,Willard Jr., Derril H.,Wright, Lois L.
, p. 978 - 983 (2007/10/03)
Starting from potent aldehyde inhibitors with poor drug properties, derivatization to semicarbazones led to the identification of a series of semicarbazone-based cathepsin K inhibitors with greater solubility and better pharmacokinetic profiles than their parent aldehydes. Furthermore, a representative semicarbazone inhibitor attenuated bone resorption in an ex vivo rat calvarial bone resorption model. However, based on enzyme inhibition comparisons at neutral pH, semicarbazone hydrolysis rates, and 13C NMR experiments, these semicarbazones probably function as prodrugs of aldehydes.
Synthesis and anti-trypanosomal activity of novel 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives
Cerecetto, Hugo,Di Maio, Rossanna,Ibarruri, Gerardo,Seoane, Gustavo,Denicola, Ana,Peluffo, Gonzalo,Quijano, Celia,Paulino, Margot
, p. 89 - 94 (2007/10/03)
Several novel semicarbazones derivatives were prepared from 5-nitro-2-furaldehyde or 5-nitrothiophene-2-carboxaldehyde, and tested in vitro as potential anti-trypanosomal agents. The compounds were prepared in good to excellent yields in 2-3 steps from readily available starting materials. Some derivatives were found to be active against Trypanosoma cruzi with an activity similar to that of Nifurtimox.
