Synthesis and structural study of a new series of 2‐methylsulfanyl‐tetrahydropyrimidines from β‐alkoxyvinyl trihalomethyl ketones

Zanatta, Nilo; Madruga, Claudia C.; Marisco, Patricia C.; Rosa, Luciana S. da; Fernandes, Liana da Silva; Flores, Darlene C.; Flores, Alex F. C.; Burrow, Robert A.; Bonacorso, Hélio G.; Martins, Marcos A. P.

doi:10.1002/jhet.5570450127

Cited by 8 publications

(1 citation statement)

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“…A variety of chemical structures identified as Cz inhibitors have been studied, such as those derived from ureas, carbazones, chalcones, carboxyamides, carboxylic acids, triazoles, vinylsulfones, hydrazones, and others (Figure 1) [14,15,16,17,18]. Among these compounds, thiazolylhydrazones have been proven powerful agents with a capacity to inhibit replication of the epimastigote (IC 50 = 0.3 μM) with a higher trypanocidal activity than benznidazole (IC 50 = 1.8 μM) [4].…”

Section: Introductionmentioning

confidence: 99%

Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors

Herrera-Mayorga

Lara-Ramírez

Chacón-Vargas

et al. 2019

IJMS

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Chagas disease (CD), or American trypanosomiasis, causes more than 10,000 deaths per year in the Americas. Current medical therapy for CD has low efficacy in the chronic phase of the disease and serious adverse effects; therefore, it is necessary to search for new pharmacological treatments. In this work, the ZINC15 database was filtered using the N-acylhydrazone moiety and a subsequent structure-based virtual screening was performed using the cruzain enzyme of Trypanosoma cruzi to predict new potential cruzain inhibitors. After a rational selection process, four compounds, Z2 (ZINC9873043), Z3 (ZINC9870651), Z5 (ZINC9715287), and Z6 (ZINC9861447), were chosen to evaluate their in vitro trypanocidal activity and enzyme inhibition. Compound Z5 showed the best trypanocidal activity against epimatigote (IC50 = 36.26 ± 9.9 μM) and trypomastigote (IC50 = 166.21 ± 14.5 μM and 185.1 ± 8.5 μM on NINOA and INC-5 strains, respectively) forms of Trypanosoma cruzi. In addition, Z5 showed a better inhibitory effect on Trypanosoma cruzi proteases than S1 (STK552090, 8-chloro-N-(3-morpholinopropyl)-5H-pyrimido[5,4-b]-indol-4-amine), a known cruzain inhibitor. This study encourages the use of computational tools for the rational search for trypanocidal drugs.

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Section: Introductionmentioning

confidence: 99%

Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors

Herrera-Mayorga

Lara-Ramírez

Chacón-Vargas

et al. 2019

IJMS

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ChemInform Abstract: Synthesis and Structural Study of a New Series of 2‐Methylsulfanyl‐tetrahydropyrimidines from β‐Alkoxyvinyl Trihalomethyl Ketones.

et al. 2008

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Fused pyrimidine derivatives R 0515Synthesis and Structural Study of a New Series of 2-Methylsulfanyl-tetrahydropyrimidines from β-Alkoxyvinyl Trihalomethyl Ketones. -A variety of novel tetrahydropyrimidines is readily obtained by reaction of trihalomethyl ketones with S-methylisothiourea (II). The cyclization of ketones (IX) and (XI) is accompanied by elimination of the trichloromethyl group. The majority of the cyclocondensation reactions proceed highly stereoselective furnishing a single isomer. A detailed structure elucidation of the reaction products is carried out. -(ZANATTA*, N.; MADRUGA, C. C.; MARISCO, P. C.; DA ROSA, L. S.; FERNANDES, L. D. S.; FLORES, D. C.; FLORES, A. F. C.; BURROW, R. A.; BONACORSO, H. G.; MARTINS, M. A. P.; J.

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Highly Chemoselective Synthesis of 6‐Alkoxy‐1‐alkyl(aryl)‐3‐trifluoroacetyl‐1,4,5,6‐tetrahydropyridines and 1‐Alkyl(aryl)‐6‐amino‐3‐trifluoroacetyl‐1,4,5,6‐tetrahydropyridines

et al. 2009

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A simple and highly chemoselective method for the synthesis of a large series of novel 6-alkoxy-1-alkyl(aryl)-3-trifluoroacetyl-1,4,5,6-tetrahydropyridines and 1-alkyl(aryl)-6-amino-3-trifluoroacetyl-1,4,5,6-tetrahydropyridines, from the reaction of 6-alkoxy-3-trifluoroacetyl-4,5-dihydro-6H-pyrans with primary alkyl and arylamines, in good yields, is reported. Preliminary in vitro antimicrobial activity of the 1-alkyl(aryl)-6-amino-

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Synthesis and structural study of a new series of 2‐methylsulfanyl‐tetrahydropyrimidines from β‐alkoxyvinyl trihalomethyl ketones

Cited by 8 publications

References 48 publications

Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors

Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors

ChemInform Abstract: Synthesis and Structural Study of a New Series of 2‐Methylsulfanyl‐tetrahydropyrimidines from β‐Alkoxyvinyl Trihalomethyl Ketones.

Highly Chemoselective Synthesis of 6‐Alkoxy‐1‐alkyl(aryl)‐3‐trifluoroacetyl‐1,4,5,6‐tetrahydropyridines and 1‐Alkyl(aryl)‐6‐amino‐3‐trifluoroacetyl‐1,4,5,6‐tetrahydropyridines

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