58990-53-7

Upstream product

• 1820-81-1 5-chlorouracil 
• 10416-59-8 N,O-bis-(trimethylsilyl)-acetamide 
• 75-77-4 chloro-trimethyl-silane 
• 1820-81-1 2,4-dihydroxy-5-chloropyrimidine 
• 999-97-3 1,1,1,3,3,3-hexamethyl-disilazane 
• 25561-30-2 N,O-Bis(trimethylsilyl)trifluoroacetamide 

Downstream Products

• 1321580-95-3 1-(3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-β-D-erythro-pentofuranos-1-yl)-5-chlorouracil 
• 2852-99-5 2′,3′,5′-tri-O-benzoyl-5-chlorouridine 
• 1351862-50-4 3-chloro-5-(4-chloro-2-(2-(5-chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy)phenoxy)benzonitrile 
• 1351862-41-3 1-(2-(2-benzyl-4-chlorophenoxy)ethyl)-5-chloropyrimidine-2,4(1H,3H)-dione 
• 1351862-52-6 3-(2-(5-chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy)-4-(3-chloro-5-cyanophenoxy)benzonitrile 
• 956478-09-4 C₃₂H₃₂ClN₃O₅S 
• 81777-50-6 1-<(2-hydroxyethoxy)methyl>-5-chlorouracil 

Relevant academic research and scientific papers

Efficient and selective catalytic N-Alkylation of pyrimidine by ammonium Sulfate?Hydro-thermal carbone under eco-friendly conditions

Abstract: An efficient and inexpensive method for the N-alkylation of pyrimidines using ammonium sulfate coated Hydro-Thermal-Carbone (HTC) (AS?HTC) as reused heterogeneous catalyst was developed. The catalyst was characterized by several analytical techniques such as SEM, XRD, and FTIR. The effect of various parameters was studied including catalyst loading, mole ratio, to achieve excellent selectivity and yields in 80–90%. Significantly, the present protocol offers the use of an inexpensive and environmentally friendly catalyst and simple workup. The simplicity of the procedure, excellent yield of the products, and the recyclability of the catalyst are the main advantages of this method. Graphic Abstract: Ammonium sulfate coated Hydro-Thermal-Carbone (HTC) (AS?HTC); an efficient and reused heterogeneous catalyst of the N-alkylation of pyrimidines was developed. Excellent selectivity and yields (80–90%) toward N1-alkylpyrimidines were achieved. Significantly, the present protocol offers the use of an inexpensive and environmentally friendly catalyst and simple workup.[Figure not available: see fulltext.]

HMDS/KI a simple, a cheap and efficient catalyst for the one-pot synthesis of N-functionalized pyrimidines

The syntheses of N-Alkylpyrimidine derivatives by reacting pyrimidin-2,4-diones with appropriate alkyl halide under microwave irradiation at 400 W were compared to the conventional synthesis route. These methodologies are regioselective and compatible with numerous substrates and furnish the corresponding N-alkylpyrimidines in good yields using a cheap catalyst HMDS/KI in MeCN. A comparison study between these two different modes of heating was investigated.

A solid-supported acidic oxazolium perchlorate as an easy-handling catalyst for the synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation

A solid-supported acidic oxazolium perchlorate was investigated as a heterogeneous catalyst in N-glycosylation reactions using silylated modified pyrimidines and an acylated ribose or glucose to afford the corresponding pyrimidine nucleosides. This salt is a nonhygroscopic and stable powder whose activity is comparable to that of 2-methyl-5-phenylbenzoxazolium perchlorate. A reaction with this polymer catalyst can be conducted on a gram scale. Reusability of the solid-supported catalyst was also investigated.

Scaffold hopping: Exploration of acetanilide-containing uracil analogues as potential NNRTIs

In order to identify novel nonnucleoside inhibitors of HIV-1 reverse transcriptase two series of amide-containing uracil derivatives were designed as hybrids of two scaffolds of previously reported inhibitors. Subsequent biological evaluation confirmed acetamide uracil derivatives 15a-k as selective micromolar NNRTIs with a first generation-like resistance profile. Molecular modeling of the most active compounds 15c and 15i was employed to provide insight on their inhibitory properties and direct future design efforts.

Synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation catalyzed by 2-methyl-5-phenylbenzoxazolium perchlorate

Several acidic azolium salts prepared from oxazole, thiazole, and imidazole derivatives were investigated as catalysts in N-glycosylation reaction using a silylated modified pyrimidine and an acylated ribose or glucose to afford the corresponding pyrimidine nucleoside. Among the salts, 2-methyl-5- phenylbenzoxazolium perchlorate showed the highest catalytic activity. This salt is a nonhygroscopic crystalline compound that shows higher activity than the frequently used trimethylsilyl triflate. Reactions with this salt can be conducted in gram scales.

Design, synthesis and biological evaluation of 2′-deoxy-2′, 2′-difluoro-5-halouridine phosphoramidate ProTides

We report the synthesis of a series of novel 2′-deoxy-2′, 2′-difluoro-5-halouridines and their corresponding phosphoramidate ProTides. All compounds were evaluated for antiviral activity and for cellular toxicity. Interestingly, 2′-deoxy-2′,2′-difluoro-5-iodo- and -5-bromo-uridines showed selective activity against feline herpes virus replication in cell culture due to a specific recognition (activation) by the virus-encoded thymidine kinase.

Computationally-guided optimization of a docking hit to yield catechol diethers as potent anti-HIV agents

A 5-μM docking hit has been optimized to an extraordinarily potent (55 pM) non-nucleoside inhibitor of HIV reverse transcriptase. Use of free energy perturbation (FEP) calculations to predict relative free energies of binding aided the optimizations by identifying optimal substitution patterns for phenyl rings and a linker. The most potent resultant catechol diethers feature terminal uracil and cyanovinylphenyl groups. A halogen bond with Pro95 likely contributes to the extreme potency of compound 42. In addition, several examples are provided illustrating failures of attempted grafting of a substructure from a very active compound onto a seemingly related scaffold to improve its activity. (Figure presented)

Synthesis of new oxabicyclo[3.3.0]octane nucleoside analogues with pyrimidine bases

Synthesis of new nucleosides with an oxabiciclo[3.3.0]octane fragment in the sugar moiety was performed by Vorbruggen nucleoside synthesis with silylated pyrimidine bases: 5-FU, 5-ClU, 5-BrU, C and 6-aza-U. The compounds were characterized by IR, MS, 1H-NMR and 13C-NMR spectra and tested for their antitumor activity comparatively with U-34 and 5IU-34. Our study points out that Cl-U-34, Br-U-34 and I-U-34 might be more efficient than U-34 against the multiplication of cancer cells, like Jurkat T lymphoblasts.

Design, synthesis and antibacterial activity of novel 1,3-thiazolidine pyrimidine nucleoside analogues

The synthesis of a new class of 1,3-thiazolidine nucleoside analogues in which furanose oxygen atom was replaced with nitrogen atom and 2′-carbon atom with sulfur atom is described. N-tert-butoxycarbonyl-2-acyloxy-4-trityloxymethyl-1,3-thiazolidine was coupled with the pyrimidine bases like uracil, thymine, etc. in the presence of lewis acids stannic chloride or trimethyl silyl triflate following Vorbruggen procedure. The antibacterial activity of the novel 1,3-thiazolidine pyrimidine nucleoside analogues is highlighted. All compounds (7a-e) with free NH group in the pyrimidine moiety showed significant biological activity against all the standard strains used and in that compounds 7d and 7e showed significant activity against 14 human pathogens tested.

Inhibition of hepatitis B virus (HBV) replication by pyrimidines bearing an acyclic moiety: Effect on wild-type and mutant HBV

Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. The main clinical limitation of a current antiviral drug for HBV, lamivudine, is the emergence of drug-resistant viral strains upon prolonged therapy. A group of 5-, 6-, or 5,6-substituted acyclic pyrimidine nucleosides with a 1-[(2-hydroxyethoxy)methyl] moiety were synthesized and evaluated for antiviral activities. The target compounds were prepared by the reaction of silylated uracils possessing a variety of substituents at the C-5 or C-6 positions or both with 1,3-dioxolane in the presence of potassium iodide and chlorotrimethylsilane by a convenient and single-step synthesis. Among the compounds tested, 5-chloro and 5-bromo analogues possessing an acyclic glycosyl moiety were the most effective and selective antiviral agents in the in vitro assays against wild-type duck HBV (EC50 = 0.4-2.2 and 3.7-18.5 μM, respectively) and human HBV-containing 2.2.15 cells (EC50 = 4.5-45.4 and 18.5-37.7 μM, respectively). These compounds were also found to retain sensitivity against lamivudine-resistant HBV containing a single mutation (M204I) and double mutations (L180M/M204V). The compounds investigated did not show cytotoxicity to host HepG2 and Vero cells, up to the highest concentration tested. The results presented here confirm and accentuate the potential of acyclic pyrimidine nucleosides as anti-HBV agents and extend our previous observations. We herein report the capability of acyclic pyrimidine nucleosides to inhibit the replication of both wild-type and drug-resistant mutant HBV.