A One-Step Synthesis of 4-Oxo-2-thioxopyrimidine Derivatives by the Ternary Condensation of Ethyl Cyanoacetate, Aldehydes, and Thiourea

Kambe, Satoshi; Saito, Koji; Kishi, Hiroshi; Sakurai, Akio; Midorikawa, Hiroshi

doi:10.1055/s-1979-28650

Cited by 89 publications

(49 citation statements)

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“…The first part of this synthesis involved the preparation of 2-chloromethyl-1H-benzo[d] imidazole 1 as previously reported 30,31) (Chart 1). The second part of this synthesis involved the preparation of different amino and mercapto pyrimidines 2a-h and 3a-h by ternary condensation of the appropriate aldehyde with thiourea or guanidine hydrochloride and ethylcyanoacetate according to reported procedures 30,[32][33][34] (Chart 1). Aiming to study the influence of substitution at different positions of the phenyl ring linked to pyrimidine, different substituted benzaldehydes were used to obtain the two series 2a-f and 3a-f.…”

Section: Resultsmentioning

confidence: 99%

“…General Method for Preparation of 4g, h To a well stirred mixture of the appropriate thiouracil 2g, h 32,33) (12.05 mmol) and anhydrous potassium carbonate (1.66 g, 12.05 mmol) in dry acetone (25 mL), a solution of 1 (2 g, 12.05 mmol) in dry acetone was added portion wise. The reaction mixture was stirred for 10 h at room temperature then heated under reflux for additional 6 h, cooled, filtered and the solid was washed with acetone.…”

Section: Preparation Of 2-((1h-benzo[d]imidazol-2-yl)methyl Thio)-16mentioning

confidence: 99%

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Synthesis, Molecular Modeling, and Biological Evaluation of Novel Benzimidazole Derivatives as Inhibitors of Hepatitis C Virus RNA Replication

Diwani¹,

Abdel‐Mohsen²,

Salama

et al. 2014

Chem. Pharm. Bull.

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In this study, synthesis and docking studies of a series of new benzimidazole derivatives linked to substituted pyrimidines either through the methylenethio linkage or its bioisosteric methylene amino bridge were carried out. All the synthesized compounds were evaluated for their hepatitis C virus (HCV) RNA replication-inhibitory activity. Compounds 4d, 4f, and 4h were found to be more potent than VX-950 (IC 50/ Key words synthesis; benzimidazole; pyrimidine; hepatitis C virus; viral RNA replication inhibitor As estimated by WHO, 170 million persons worldwide are infected with hepatitis C virus (HCV) which causes chronic liver disease. HCV is a positive stranded RNA virus and is a member of the Flaviviridae family of viruses.1,2) Combined therapy of HCV infections with pegylated alpha interferon (IFN-α) and ribavirin is only effective in 50-60% of infected individuals and is associated with serious side effects such as depression, flu-like symptoms, fatigue and hemolytic anemia caused by ribavirin. 3,4)There is an unmet need for potent and selective inhibitors of HCV replication. Significant research efforts are currently directed towards targeting viral enzymes especially NS3-4A serine protease [5][6][7][8] and NS5B RNA-dependent RNA polymerase which are both required for virus propagation. 9-11)The NS3-4A serine protease has been an attractive target in the development of new antivirals with activities against HCV since it is essential for viral replication.9-11) The serine protease activity of NS3 in complex with the NS4A cofactor is responsible for the proteolytic cleavage at four junctions of the HCV polyprotein precursor: NS3-NS4A (self cleavage), NS4A-NS4B, NS4B-NS5A, and NS5A-NS5B. 7,[12][13][14][15][16][17] Crystal structure of the serine protease domain of the NS3, with its essential cofactor NS4A, 18,19) revealed that the NS3-4A complex adopts a chymotrypsin/trypsin-like fold with structurally conserved regions typical of small chymotrypsin-like proteases. 20,21) The N-terminal region of NS3-4A (residues 1-93 of NS3 and residues 21-34 of NS4A) contains an eightstranded β-barrel motif, with one of the strands contributed by the NS4A cofactor.20) The C-terminal region (residues 94-175) contains a six-stranded-barrel that ends with a helix. The active site (His: 57, Asp: 81, and Ser: 139) is located between these two regions and is formed by a shallow solvent exposed pocket to which the inhibitors bind in an extended conformation. 18-21)Sofosbuvir (GS-7977), a uridine nucleotide analogue, and an inhibitor of HCV NS5B polymerase is effective against HCV genotypes 1, 2, 3, 4, and 6. Sofosbuvir, especially in interferon-free combinations, represents a very promising option in the treatment of chronic hepatitis C. 22)Currently, different anti-HCV treatments depend on the inhibition of HCV NS3-4A serine protease. Telaprevir (VX-950), boceprevir and BILN 2061 (Fig. 1) are examples of well known HCV NS3-4A serine protease inhibtors. 23,24) Telaprevir, a small molecule peptidomimetic, forms a covalent but revers...

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Section: Resultsmentioning

confidence: 99%

Section: Preparation Of 2-((1h-benzo[d]imidazol-2-yl)methyl Thio)-16mentioning

confidence: 99%

Synthesis, Molecular Modeling, and Biological Evaluation of Novel Benzimidazole Derivatives as Inhibitors of Hepatitis C Virus RNA Replication

Diwani¹,

Abdel‐Mohsen²,

Salama

et al. 2014

Chem. Pharm. Bull.

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“…All reactions were carried out under an air atmosphere. 5-Cyano-4-oxo-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine 1 was synthesized via a multicomponent reaction (MCR) by a one pot condensation reaction according to the literature; 31 (4). A mixture of compound 3 (20 g, 66 mmol) in an excess amount of phosphorus oxychloride (60 ml) was heated under reflux on a water bath for 5 h. After cooling, the reaction mixture was poured into an ice-cooled water mixture (600 g), and then neutralized using sodium carbonate solution.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and antimicrobial activity of some new thienopyrimidine derivatives

Tolba¹,

El‐Dean²,

Ahmed³

et al. 2017

Arkivoc

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“…The reaction of malononitrile with phenyl isothiocyanate in the presence of potassium hydroxide afford the potassium salt of ketene N,S-acetal (39). Compound (39) was allowed to react with p-bromophenacyl bromide or chloroacetone to afford the S-alkylated derivatives (40) which underwent cyclization in the presence of sodium ethoxide into compound (41).…”

Section: From O-ketoaminothiophenementioning

confidence: 99%

Synthesis of Thienopyrimidine Derivatives Starting From Thiophene Ring and Pyrimidine Ring

Saddik

2017

ECB

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Thienopyrimidines derivatives continue to attract great interest due to the wide variety of interesting biological activities observed for compounds characterized by this heterocyclic system. This review results from the literature survey containing the synthesis of thieno [2,3-d]pyrimidines, thieno[3,2-d]pyrimidines and thieno [3,4-d]pyrimidines from thiophene ring then build pyrimidine ring and from pyrimidine ring then build thiophene ring. * Corresponding Authors

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A One-Step Synthesis of 4-Oxo-2-thioxopyrimidine Derivatives by the Ternary Condensation of Ethyl Cyanoacetate, Aldehydes, and Thiourea

Cited by 89 publications

References 0 publications

Synthesis, Molecular Modeling, and Biological Evaluation of Novel Benzimidazole Derivatives as Inhibitors of Hepatitis C Virus RNA Replication

Synthesis, Molecular Modeling, and Biological Evaluation of Novel Benzimidazole Derivatives as Inhibitors of Hepatitis C Virus RNA Replication

Synthesis and antimicrobial activity of some new thienopyrimidine derivatives

Synthesis of Thienopyrimidine Derivatives Starting From Thiophene Ring and Pyrimidine Ring

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