2-thiouracil Derivatives Research Articles

Synthesis and phosphonylation of <i>S</i>-methylthiouracil and its derivatives

A series of S -methylated derivatives of 2-thiouracil were prepared and then phosphonylated with diethyl chlorophosphate. The reaction conditions were optimized, the structure of the obtained compounds was determined by 1Н, 13С, 31Р NMR spectroscopy methods.

AMINATION OF 2-(2-OXO-2-ARYLETHYLTHIO)-PYRIMIDIN-4(3H)-ONE DERIVATIVES USING THE SULFONATE METHOD

A Derivatives of 2-thiouracil are characteri­zed by wide spectrum of biological activity, which is characteristic of most representatives this heterocycles class. In particular, 2-(2-oxo-2-phenylethylthio)-pyrimi­din-4(3H)-ones belong to the group of non-nucleoside inhibitors of HIV-1 reverse transcriptase. The antimalarial properties of 2-(2-oxo-2-phenylethyl­thio)-4-R-pyrimidine derivatives, which proved to be effective inhibitors of CIpP protease of Plasmodium falciparum, are being studied. Known examples of 2-(2-oxo-2-phenylethyl­thio)-pyrimidines modification at the "4" position of the heterocycle are limited to use 4-chloro derivatives, which, in turn, are formed according to the classical method by reaction of pyrimidine-4(3H)-ones with POCl3 at boiling point of reaction mixture. In this work, we present an alternative version of modification the above-mentioned class of compounds. By amination amide function of 6-R-2-(2-oxo-2-arylethylthio)-pyrimidin-4(3H)-ones derivati­ves of with ethanolamine and 1-aminopropa­ne-2,3-diol using sulfonate method, synthesized and characterized new compounds a 6-R-2-(2-oxo-2-phenylethylthio)-pyrimidines series by spectral methods. The advantages of this scheme are discussed (the formation of intermediate sulfonates and the amination stage do not require harsh conditions and are carried out with satisfactory yields). The proposed scheme can be recommended in cases where the original substrate contains functio­nal groups that are labile at high temperatures and sensitive to an acidic environment.

Some Features of the Tscherniac‒Einhorn Reaction with 2-Thiouracil Derivatives

The Tscherniac–Einhorn reaction of 6-methyl and 6-(trifluoromethyl) derivatives of 2-thiouracil with N-(bromomethyl)phthalimide in under basic catalysis leads to the formation of S-amidomethylation products. When using 6-amino-2-thiouracil, decomposition of the alkylation products occurs. An in vitro study of the compounds obtained showed their lack of cytotoxicity and anti-HIV-1/2 activity.

Synthesis and Antiglycation Activity of Novel S-Carboxyalkyl Derivatives of 2-Thiouracil

S-carboxyalkyl derivatives of 2-thiouracil were synthesized and their pharmacological activity was studied. Several of the compounds were characterized by antiglycation activity. These compounds had no effect on PPAR or glucokinase activity and had weak activity in cleaving protein crosslinks.

Synthesis, antimicrobial activity and high cell viability of copper derivatives of 2-thiouracil, purine-6-thione and 2,4,6-trimercaptotriazine

Reactions of copper(II) acetate with 2-thiouracil (tucH2) and triphenyl phosphine (1:1:1 or 1:1:2 molar ratios) in methanol-acetonitrile/chloroform mixture yielded a light brown N,S-bridged dinuclear CuI complex, [Cu(PPh3)2(µ-N,S-tucH)Cu(PPh3)2Cl] 1, incorporating uninegative 2-thiouracilate. X-ray crystallography has shown that the crystals of complex 1 comprise a two component twin system and belong to the space group Ia. The major component 1a is about 77% and the minor component 1b is about 23%. One Cu is four-coordinate tetrahedral with center {CuP2SCl} and the other Cu is three-coordinate distorted trigonal planar with {CuP2N} center. Crystal data: 1, formula, C76H63ClCu2N2OP4S; space group: Ia; monoclinic, a, 22.2638(9); b, 11.8050(4); c, 27.4455(10) Å; β, 113.358(5); R, 4.80%;173(2) K. The antimicrobial activities of dinuclear 1 as well as that of the previously reported 2-thiouracil, 2,4,6-trimercaptotriazine (tmtH3) and purine-6-thione (purSH2) complexes, [CuCl(κ1-S-tucH2)(PPh3)2] 2, [Cu2Br2(μ-S-tucH2)2(PPh3)2] 3, [Cu(tmtH2)(PPh3)2] 4, [Cu3Br2(k1-N,k1-S,µ-S-tmtH2)(PPh3)6] 5 and [Cu(k1-N,k1-S-purSH)(PPh3)2] 6, have been screened against gram negative, Escherichia coli (MTCC 119) and Shigella flexneri (MTCC 1457), gram positive, Enterococcus faecalis (MTCC 439) and Staphylococcus aureus (MTCC 740) microorganism. High percentage of cell viability (96–97%) is observed in some cases.

ChemInform Abstract: Boron-Containing Thiouracil Derivatives for Neutron-Capture Therapy of Melanoma.

Boron-containing derivatives of 2-thiouracil and 2,4-dithiouracil and the corresponding 6-propyl compounds, containing a dihydroxyboryl group in the 5-position, have been prepared. These compounds accumulate in B16 melanoma in mice in concentrations up to 30 micrograms of boron per gram tissue. The uptake persists. The toxicity of both 2-thiouracil derivatives is low. These compounds are therefore good candidates for boron neutron-capture therapy of malignant melanoma.

A practical synthesis and spectroscopic study of new potentially biologically active S-lithocholic acid-substituted derivatives of 2-thiouracil

Abstract Five new S -3α-acetoxy-5β-lithocholic acid methyl ester-substituted derivatives of 2-thiouracil and 6-methyl-2-thiouracil have been prepared. 5-Morpholino-methyl-2-thiouracil, 5-piperidinomethyl-2-thiouracil, and 5-(4-methylpiperidino)methyl-2-thiouracil have been obtained via the Mannich reaction between 6-methyl-2-thiouracil, paraformaldehyde, and the cyclic secondary amines morpholine, piperidine, or 4-methylpiperidine in ethanol. The structures of the compounds were confirmed by spectral ( 1 H NMR, 13 C NMR, and FT-IR) analyses and mass spectrometry. Estimation of the pharmacotherapeutic potential has been accomplished for the synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS).

Preparation of [76Br] 5-bromo-2-thiouracil, a positron-emitting melanoma localizing agent

Derivatives of 2-thiouracil are known to incorporate into the growing melanin pigment of melanomas as false melanin precursors. Animal and pilot patient studies have demonstrated, that radioiodinated 5-iodo-2-thiouracil is a promising agent for visualization of melanotic melanomas. In this study, 2-bromo-2-thiouracil was labeled using the positron-emitting isotope 76Br (T 1/2 = 16.2 h), which potentially enables to use such advantages of PET as superior spatial resolution and possibility to quantify radioactivity concentration in vivo. The use of Chloramine-T as oxidant provided a labeling efficiency of about 70%.

Synthesis and spectral characteristics of organometallic derivatives of 2-thioquinazolinone: influence of metallation on tautomerism

The compounds R n MHTQ (R=Me, Ph; n=1 (M=Hg), 2 (M=TI); H 2TQ=2-thioquinazolinone) and (RHg) 2TQ (R=Me, Ph) have been prepared and their coordinative characteristics studied using vibrational (IR and Raman) and NMR ( 1H, 13C, 205TI) spectroscopy. Spectroscopic data in DMSO solution indicate that these complexes are closer to the enol form than the corresponding derivatives of 2-thiouracil.

Boron-containing thiouracil derivatives for neutron-capture therapy of melanoma

Boron-containing derivatives of 2-thiouracil and 2,4-dithiouracil and the corresponding 6-propyl compounds, containing a dihydroxyboryl group in the 5-position, have been prepared. These compounds accumulate in B16 melanoma in mice in concentrations up to 30 micrograms of boron per gram tissue. The uptake persists. The toxicity of both 2-thiouracil derivatives is low. These compounds are therefore good candidates for boron neutron-capture therapy of malignant melanoma.

The tautomeric equilibria of thio analogues of nucleic acid bases. Part 1. 2-Thiouracil: background, preparation of model compounds, and gas-phase proton affinities

The preparation is reported of all four of the monoalkyl derivatives of 2-thiouracil and of four of the six possible dialkyl derivatives required as models for a study of the tautomeric equilibria by physical methods. Gas-phase proton affinities are determined using ion cyclotron resonance mass spectrometry, and are used to provide quantitative estimates of individual tautomer stabilities in the vapour state. These quantitative results agree well with qualitative deductions of predominant structures for the monoalkyl derivatives from i.r. spectroscopy.

Organomercury(II) derivatives of 2-thiouracil. An infrared and proton magnetic resonance study of structures

The novel complexes RHg(s 2UraH −1) (R = Me, Ph) where s 2UraH −1 is the monoanion of 2-thiouracil, have been synthesized. Comparison of the infrared spectra of the solid complexes and of 1H nuclear magnetic resonance spectra of the complexes in dimethyl-d 6 sulfoxide with spectra of s 2 Ura and Na[s 2UraH −1] allows the recognition of the existence of isomers in the solid, with bonding to exocyclic sulfur and to pyrimidine nitrogens. In solution, a simpler pattern is observed, with 2J( 1H 199Hg) indicating bonding to sulfur only.

Methods of activating S-methylmercapto derivatives of purine and pyrimidine in reactions with weakly nucleophilic compounds

The authors have found that mercuric chloride has a catalytic effect on animation of 6-methylmercapto-purine by aromatic amines and on alcoholysis of S-methyl derivatives of 2-thiouracil and 2-thio-6-methyl-uracil. 2. Introduction of an acetyl group in the 9 position activates 6-methylmercaptopurine in amination.

Nucleic acid components and their analogues. CXI. Decyanoethylation of the cyanoethyl derivatives of uracil, 2-thiouracil, and 6-azauracil

Nucleic acid components and their analogues. CXI. Decyanoethylation of the cyanoethyl derivatives of uracil, 2-thiouracil, and 6-azauracil