Amino Uracil Research Articles

Synthesis of Selenocyanates and Selenoethers of Amino Pyrazoles and Amino Uracils by In Situ Triselenium Dicyanide from Malononitrile and Selenium Dioxide.

Herein, we report an efficient method for synthesis of novel selenocyanates of amino pyrazole, amino uracil, and amino isoxazole derivatives using in situ triselenium dicyanide from the combination of malononitrile and selenium dioxide in DMSO medium. Using the same combination but changing the stoichiometry of reagents and sequence of addition and temperature, symmetrical selenoethers of amino pyrazoles and amino uracils were prepared in good yields. Furthermore, selenocyanates of amino pyrazoles were utilized for the synthesis of corresponding alkynyl selenides in the presence of CuI and Cs2CO3. The salient features of this methodology are inexpensive starting materials, short reaction time, and good to very good yields. This method is also applicable for the gram-scale synthesis of selenocyanates of amino pyrazoles and amino uracils.

Electro-organic synthesis of C-5 sulfenylated amino uracils: Optimization and exploring topoisomerase-I based anti-cancer profile

Cancer is spreading worldwide and is one of the leading causes of death. The use of existing chemotherapeutic agents is frequently limited due to side effects. As a result, it is critical to investigate new agents for cancer treatment. In this context, we developed an electrochemical method for the synthesis of a series of thiol-linked pyrimidine derivatives (3a-3p) and explored their anti-cancer potential. The biological profile of the synthesized compounds was evaluated against breast (MDAMB-231 and MCF-7) and colorectal (HCT-116) cancer cell lines. 3b and 3d emerged to be the most potent agents, with IC50 values ranging between 0.98 to 2.45 µM. Target delineation studies followed by secondary anticancer parameters were evaluated for most potent compounds, 3b and 3d. The analysis revealed compounds possess DNA intercalation potential and selective inhibition towards human topoisomerase (hTopo1). The analysis was further corroborated by DNA binding studies and in silico-based molecular modeling studies that validated the intercalating binding mode between the compounds and the DNA.

Electro-Organic Synthesis of C-5 Sulfenylated Amino Uracils: Optimization and Exploring Topoisomerase-I Based Anticancer Profile

Electro-Organic Synthesis of C-5 Sulfenylated Amino Uracils: Optimization and Exploring Topoisomerase-I Based Anticancer Profile

DFT Analysis and Synthesis of Medicinally Important Pyrrolo[2,3-d]Pyrimidines by Using Thiamine Hydrochloride as a Recyclable Organocatalyst in Aqueous Media

A facile, environmentally benign and proficient route has been developed for the diverse synthesis of pyrrolo[2,3-d]pyrimidine derivatives followed by heterocyclization starting from Amino uracil, arylgyoxal and malononitrile/thiols. Readily available thiamin hydrochloride organocatalyst was used as a green promoting medium. As well as the reaction progress was taken place under aqueous media. This procedure also offers a base and metal free approach which endowed high yields with better functional group tolerating ability and mild reaction conditions. Further, methodology had a widescope with recyclability and reuse of thiamin hydrochloride. DFT/TD-DFT calculations with B3LYP/6-311G++ level of theory were used to study the optimized geometry and HOMO-LUMO energy of the synthesized compounds (4b and 6i).

Visible Light-Mediated C(sp2)-H Selenylation of Amino Pyrazole and Amino Uracils in the Presence of Rose Bengal as an Organophotocatalyst.

Herein, we report an efficient methodology for the synthesis of alkyl, benzyl, and phenyl selenoethers of aminopyrazoles and aminouracils by C(sp2)-H functionalization in the presence of visible light and Rose Bengal as an organophotocatalyst. The reaction of amino pyrazole/iosothiazole/isoxazole or amino uracils with 0.5 equivalent of diphenyl/dibenzyl/diethyl diselenides in the presence of visible light in acetonitrile medium and a catalytic amount of Rose Bengal provided the corresponding phenyl, benzyl, or ethyl selenoethers in good to very good yields. We have also utilized some of the selenylated aminopyrazoles for the preparation of pyrazole-fused dihydropyrimidines tethered with arylselenoethers by a catalyst-free one-pot three-component reaction. The notable features of this methodology are metal-free reaction conditions, good to very good yields, use of an organic photocatalyst, and wide substrate scope; it is also applicable to gram-scale synthesis and provides selenoethers of medicinally important heterocycles such amio-pyrazole, isoxazole, isothiazole, and uracils.

Hydrogen Peroxide-Mediated Rapid Room Temperature Metal-Free C(sp2)-H Thiocyanation of Amino Pyrazoles, Amino Uracils, and Enamines.

A rapid metal- and additive-free room temperature method for C(sp2)-H thiocyanation of aminopyrazoles, aminoisoxazole, aminoisothiazole, amino uracils, and aliphatic enamines has been developed in an aqueous medium using hydrogen peroxide as a benign oxidant and ammonium thiocyanate as a thiocyanating agent. On the other hand, the reaction of hydrogen peroxide and ammonium thiocyanate followed by one-pot addition of NaOH provides the corresponding disulfides in the case of amino azoles, and pyrimidine-fused 2-amino thiazoles were observed in the case of aminouracils. The salient features of this method are the use of an eco-friendly oxidant, reaction tunability to access different products, wide substrate scope, and good to very good yields.

Synthesis of Thio and Selenoethers of Cyclic β-Hydroxy Carbonyls and Amino Uracils: A Metal-Free Regioselective I2 /DMSO Mediated Reaction

A simple and practical method has been developed using I2/DMSO for the construction of C−S and C−Se bonds in pharmaceutically important cyclic β-hydroxy carbonyls such as 4-hydroxy-6-methyl-2H-pyran-2-one, 4-hydroxy-1-methylquinolin-2(1H)-one, quinoline-2,4-diol and heterocyclic enamines such as amino uracil and amino pyrazole derivatives under mild reaction conditions. A series of thio and seleno ethers have been synthesized directly from thiols and selenols in the presence of in situ iodonium ion generated from the I2/DMSO combination in good to very good yields. This metal-free dehydrogenative C−S and C−Se coupling reaction goes via C(sp2)-H bond activation and works under conventional as well as microwave heating. Under microwave conditions, reactions complete within 15 minutes with very good yields.

Synthesis of Novel 5,6-Disubstituted Pyrrolo [2,3-d]Pyrimidine-2,4-Diones Via One-Pot Three-Component Reactions.

A simple and novel method for the synthesis of 5,6-disubstituted pyrrolo[2,3-d]pyrimidine-2,4-diones has been reported using arylglyoxal-based three-component reactions. Under microwave heating conditions, arylglyoxal, 6-amino uracil, or its derivatives reacts with various thiols in acetic acid medium to provide a series of pyrrolo[2,3-d]pyrimidine-2,4-diones (4) having a thioether and an aryl ring in 5 and 6 positions, respectively. On the other hand reaction of arylglyoxal, amino uracil and malononitrile in place of thiols, provided corresponding 5,6-disubstituted pyrrolo[2,3-d]pyrimidine-2,4-diones (5) with selectively converting one of the -CN to -CONH2 group both in conventional (method A) and microwave heating conditions (method B). This methodology is a simple and efficient protocol for the synthesis of diverse 5,6-disubstituted pyrrolo[2,3-d]pyrimidine-2,4-diones from the readily available starting materials in good yields.

Simple Three-Component Method for the Synthesis of Spiroindeno[1,2-b]pyrido[2,3-d]pyrimidine-5,3′-indolines

An efficient, simple, and catalyst-free synthesis of spiroindeno[1,2-b]pyrido[2,3-d]pyrimidine-5,3'-indolines and spiroacenaphthylene-1,4'-indeno-1,5'-pyrido[2,3-d]pyrimidines by the three-component reaction of 1,3-indandione, amino uracils and isatins or acenaphthylene-1,2-dione in refluxing ethanol is reported.

An Efficient Regiospecific Synthesis of Highly Functionalized Novel Dihydropyrimido[4,5-d]pyrimidine Derivatives by a Three-Component One-Pot ­Condensation under Solvent-Free Conditions

The environment-friendly three-component condensation of 6-[(dimethylamino)methylene]amino uracil, an aldehyde, and ammonium acetate in the presence of acetic acid afforded a one-pot synthesis of biologically significant novel dihydropyrimido[4,5-d]pyrimidine derivatives in high yields under solvent-free conditions.

Regiospecific one-pot synthesis of pyrimido[4,5-d]pyrimidine derivatives in the solid state under microwave irradiations

Electron rich 6-[(dimethylamino)methylene]amino uracil 1, undergoes [4+2] cycloaddition reactions with various in situ generated glyoxylate imine and imine oxides 6 to provide novel pyrimido[4,5-d]pyrimidine derivatives of biological significance, after elimination of dimethylamine from the (1:1) cycloadducts and oxidative aromatisation. This procedure provides a convenient method for the direct synthesis of pyrimido[4,5-d]pyrimidines in excellent yields when carried out in the solid state and under microwave irradiations.

“Tertiary amine effect” strategy in the synthesis of novel uracil analogues

6-Tertiary amino uracils 1 react with dimethyl acetylenedicarboxylate 2 to give 4,5-dihydropyrrolo[2,3-d]pyrimidine 3 and 4,5,6,7,8-pentahydropyrrolizino[2,3-d]pyrimidine analogues 5 in excellent yields.

Annelation of 5 or 6 membered heterocycles to uracil derivatives via phosgeniminium salt(1) condensation

AbstractPI salts condense with 1, 3‐dimethyl barbituric acid and 1, 3‐dimethyl‐4 ‐amino uracil to give new amide chlorides 4 and 5. These synthons lead to new aminated isoxazolo‐, or pyrimido‐ and pyrido‐pyrimidines 12, 16 & 18 on cyclisation with hydroxylamine, cyanamide and malononitrile, respectively.

Differences in mitotic cycle in various tissues of Vicia faba roots as revealed by 5-amino uracil synchronization of cell division

Longitudinal sections of lateral roots of Vicia faba, pre-treated with 5-amino uracil, were analyzed for the appearance of areas of synchronized cell division. The first evidence of a recovery from the inhibitory effect of amino uracil is seen in the pre-cortical tissues proximal to the root initials. This zone of cell division moves distally toward the apex. Cell division begins in the central cylinder later than in the cortex and moves distally to the pole, ultimately including all the apex except for a small field of interphase cells in the quiescent center.

Antitumor activity of 5-bis(2-chloroethyl) amino uracil against sarcoma 180 and Ehrlich carcinoma.

Conclusions5-Bis(2-chloroethyl) amino uracil (U-8344) is an effective agent against the solid and ascites forms of Ehrlich carcinoma and Sarcoma 180 under specified conditions.