7391-70-0Relevant academic research and scientific papers
Synthesis and antifungal activity of substituted 2,4,6-pyrimidinetrione carbaldehyde hydrazones
Neumann, Donna M.,Cammarata, Amy,Backes, Gregory,Palmer, Glen E.,Jursic, Branko S.
, p. 813 - 826 (2014/01/23)
Opportunistic fungal infections caused by the Candida spp. are the most common human fungal infections, often resulting in severe systemic infections - a significant cause of morbidity and mortality in at-risk populations. Azole antifungals remain the mainstay of antifungal treatment for candidiasis, however development of clinical resistance to azoles by Candida spp. limits the drugs' efficacy and highlights the need for discovery of novel therapeutics. Recently, it has been reported that simple hydrazone derivatives have the capability to potentiate antifungal activities in vitro. Similarly, pyrimidinetrione analogs have long been explored by medicinal chemists as potential therapeutics, with more recent focus being on the potential for pyrimidinetrione antimicrobial activity. In this work, we present the synthesis of a class of novel hydrazone-pyrimidinetrione analogs using novel synthetic procedures. In addition, structure-activity relationship studies focusing on fungal growth inhibition were also performed against two clinically significant fungal pathogens. A number of derivatives, including phenylhydrazones of 5-acylpyrimidinetrione exhibited potent growth inhibition at or below 10 μM with minimal mammalian cell toxicity. In addition, in vitro studies aimed at defining the mechanism of action of the most active analogs provide preliminary evidence that these compound decrease energy production and fungal cell respiration, making this class of analogs promising novel therapies, as they target pathways not targeted by currently available antifungals.
Development of pharmaceutical drugs, drug intermediates and ingredients by using direct organo-click reactions
Ramachary, Dhevalapally B.,Kishor, Mamillapalli,Reddy, Y. Vijayendar
supporting information; experimental part, p. 975 - 993 (2009/04/11)
Here we report on our studies of the use of combinations of amino acids, amines, K2CO3 or Cs2CO3 and CuSO4/Cu for catalysing green cascade reactions. We aimed to prepare the highly reactive and substituted olefin species 7 and 8, under very mild and environmentally friendly conditions, thus giving the hydrogenated products 10 and 12 through the action of Hantzsch ester (4) by self-catalysis through decreasing the HOMO-LUMO energy gaps between olefins 7/8 and Hantzsch ester (4) through biomimetic reductions. Highly useful compounds 10 to 14 were assembled from simple substrates such as aldehydes 1, ketones 2, CH acids 3, Hantzsch ester (4) and alkyl halides 5 by diversity-oriented green synthesis involving cascade olefination/hydrogenation (O/H), olefination/hydrogenation/alkylation (O/H/A) and hydrogenation/olefination/hydrogenation (H/O/H) reaction sequences in one-pot fashion with stereospecific organo- and organo-/metal-carbonate catalysis. Highly functionalized diverse compounds such as 10 to 14 are biologically active products and have found wide applications as pharmaceutical drugs, drug intermediates and drug ingredients. For the first time in organocatalysis, we report the O/H/A/TE reaction to furnish high yields of transesterification products 11 by simply mixing the reactants under proline/K2CO3 catalysis conditions. Additionally, a novel organocatalytic H/O/H reaction sequence for the synthesis of alkyl-substituted aromatics has been developed. Furthermore, for the first time we have developed organocatalysed cascade olefination/hydrogenation/hydrolysis (O/H/H) reactions to furnish highly useful materials such as 2-oxochroman-3-carboxylic acid (14kc) and 2-amino-4H-chromene-3-carbonitrile (14kj) in good yields. Experimentally simple and environmentally friendly organocatalytic two-carbon homologation through cascade O/H/H reactions of aldehydes 1, Meldrum's acid (3c), Hantzsch ester (4) and acetic acid/triethylamine in ethanol has been demonstrated. Additionally, we have developed a green synthesis of the highly substituted 1,2,3-triazole 17 from simple substrates through a two-step combination of olefination/hydrogenation/alkylation and Huisgen cycloaddition reaction sequences under stereospecific organocopper catalysis conditions. In this paper we have found strong support for our hypothesis that, "decreasing the HOMO-LUMO energy gap between olefins 7/8 and Hantzsch ester (4) will drive the biomimetic hydrogenation reaction by self-catalysis". This self-catalysis was further confirmed with many varieties of examples. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
Development of drug intermediates by using direct organocatalytic multi-component reactions
Ramachary, Dhevalapally B.,Kishor,Reddy, G. Babul
, p. 1641 - 1646 (2008/02/03)
Development of drug intermediates by using direct amino acid organocatalytic multi-component reaction was investigated. Hydrogenations of double-bond containing compounds including carbonyls, imines and olefins are important for living organisms as well as for the industrial production of chemicals. Amino acid catalysis has emerged as a powerful green synthetic tool for the development of both achiral and chiral catalysis of condensations and cycloadditions and the 1,2- and 1,4-additions of enals, enones and ketones including electrophiles. It was found that the amino acid proline 4a catalyzes the Knoevenagel condenstion of cyclohexanone 1a with the CH-acid ethyl cyanoacetate 2a to furnish the active olefin 9aa. This simple and environmentally friendly approach can be used to construct highly substituted hydrogenated products in a regioselective fashion with good yields.
Reductive C-alkylation of barbituric acid derivatives with carbonyl compounds in the presence of platinum and palladium catalysts
Jursic, Branko S.,Neumann, Donna M.
, p. 4103 - 4107 (2007/10/03)
Effective synthetic procedures for the preparation of mono- and di-C-alkylated barbituric acid derivatives through palladium and platinum catalytic hydrogenation of solutions of barbituric acids (unsubstituted, N-mono, and N,N′-disubstituted barbituric acids) and carbonyl compounds (aliphatic and aromatic aldehydes and ketones).
