- Synthesis and Plant Growth Stimulating Action of 2-Amino-6-methylpyrimidine-4(3H)-thione Derivatives
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Abstract: A series of new pyrimidine derivatives, including those containing an azole or azine heterocycle linked through a sulfur atom or a thiomethylene group, was synthesized based on 2-amino-6-methylpyrimidine-4(3H)-thione. The synthesized compounds exhibited a pronounced stimulating effect on plants growth in the range of 43–96% compared to heteroauxin.
- Hambardzumyan, E. N.,Shahbazyan, L. V.,Vorskanyan, A. S.,Yengoyan, A. P.
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- Synthesis, crystal structure, and ADME prediction studies of novel imidazopyrimidines as antibacterial and cytotoxic agents
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In the present study, a novel series of polyfunctionalized imidazopyrimidines 6a–u and 9a–d were efficiently constructed by a domino reaction between 2-imino-6-substituted-2,3-dihydropyrimidin-4(1H)-ones 4a–d or 8a–c and 2-bromoacetophenones 5a–i under mild basic conditions. The synthesized series were screened for their antibacterial activity against Staphylococcus aureus and Bacillus subtilis as Gram-positive (+) bacteria, as well as against Gram-negative (?) bacteria Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella typhi. Most of the synthesized derivatives of imidazopyrimidines 6 and 9 showed remarkable selectivity against Gram(?) bacteria over the Gram(+) ones. Compounds 6c, 6f, and 6g displayed potent and broad-spectrum antibacterial activity against all tested strains. Compounds 6f and 6g displayed promising inhibitory activity on GryB ATPase from E. coli with IC50 = 1.14 and 0.73 μM, respectively. Simultaneously, some of the synthesized imidazopyrimidines were screened for their antiproliferative activity against 60 cancer cell lines at a concentration of 10 μM. Compound 9d showed potent activity against most of the tested cell lines, with a mean growth inhibition of 37%. The ADME (absorption, distribution, metabolism, and excretion) prediction study demonstrated that the synthesized hits have, in addition to their promising chemotherapeutic activity, acceptable pharmacokinetic properties, and a drug-likeness nature to be further developed.
- Abdel-Mohsen, Heba T.,Abood, Amira,El Diwani, Hoda I.,Flanagan, Keith J.,Meindl, Alina,Senge, Mathias O.
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- Regioselective synthesis of 6-substituted-2-amino-5-bromo-4(3H)- pyrimidinones and evaluation of their antiviral activity
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A series of 2-amino-5-bromo-4(3 H)-pyrimidinone derivatives bearing different substituents at the C-6 position were synthesized using a highly regioselective lithiation-substitution protocol, and the effect of structural variation at the C-6 position on their antiviral activity in cell culture was evaluated. Although some of the derivatives were found to be active against various virus strains, they were effective only close to their toxicity threshold.
- Singh, Kamaljit,Singh, Kawaljit,Balzarini, Jan
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- 2-Pivalamido-3H-pyrimidin-4-one derivatives: Convenient pivalamide hydrolysis using Fe(NO3)3 in MeOH
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A simple methodology for pivalamide (trimethylacetamide, pivaloylamino) hydrolysis has been discovered using Fe(NO3)3 in MeOH at room temperature. The pivalamido group of 2-pivalamido-3H-pyrimidin-4-ones or fused 2-pivalamido-3H-pyrimidin-4-ones such as 2-pivalamido-3H-quinazolin-4-ones and 2-pivalamido-3H-pteridines have been hydrolysed under these conditions to afford the corresponding amine.
- Bavetsias,Henderson,McDonald
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- Theoretical investigation on the reactivity and photophysical properties of cobalt(II) and manganese(II) complexes constructed using Schiff base ligands based on ALIE and TDDFT calculations
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Herein, we describe the synthesis of two novel Schiff base ligands, 2-[(3-bromo-5-hydroxybenzylidene)-amino]-6-methylpyrimidin-4-ol (1) and 3-bromo-5-[(5-methylthiazol-2-ylimino)methyl]phenol (2), and their Co(II) and Mn(II) complexes (4–6). The molecular
- Prasad, Kollur Shiva,Pillai, Renjith Raveendran,Armakovi?, Stevan,Armakovi?, Sanja J.
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- Ultrasound-assisted rapid synthesis of 2-aminopyrimidine and barbituric acid derivatives
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Novel, inexpensive, and relatively expeditious procedure to achieve the synthesis of different 2-aminopyrimidine and barbituric acid derivatives is presented here, starting from readily available compounds such as guanidine hydrochloride, urea, 1,3-dialkylurea, or thiourea. Under ultrasonic irradiation, base-driven (Na2CO3, NaOH, or NaOC2H5) heterocyclization reactions of the aforementioned substrates with diethyl malonate, diethyl-2-alkyl malonate, pentane-2,4-dione, or ethyl-3-oxobutanoate yielded corresponding products. Significant advantages of this sonochemical synthetic protocol with regard to the conventional thermal methods include easy reaction setup and work-up steps, reasonably mild conditions, shorter reaction times (～30 min) and comparably high product yields. The characterization of the synthesized compounds was based on melting points, FT-IR, GC-MS, 1H-NMR techniques, and the obtained data were also checked from the previously published studies.
- Bayramo?lu, Duygu,Kurtay, Gülbin,Güllü, Mustafa
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p. 649 - 658
(2020/02/11)
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- Synthesis and Investigation of Phthalazinones as Antitubercular Agents
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A series of 2- and 7-substituted phthalazinones was synthesised and their potential as anti-tubercular drugs assessed via Mycobacterium tuberculosis (mc26230) growth inhibition assays. All phthalazinones tested showed growth inhibitory activity (MIC 100 μm), and those compounds containing lipophilic and electron-withdrawing groups generally exhibited better anti-tubercular activity. Several lead compounds were identified, including 7-((2-amino-6-(4-fluorophenyl)pyrimidin-4-yl)amino)-2-heptylphthalazin-1(2H)-one (MIC=1.6 μm), 4-tertbutylphthalazin-2(1H)-one (MIC=3 μm), and 7-nitro-phthalazin-1(2H)-one (MIC=3 μm). Mode of action studies indicated that selected pyrimidinyl-phthalazinones may interfere with NADH oxidation, however, the mode of action of the lead compound is independent of this enzyme. MIC=minimum inhibitory concentration.
- Santoso, Kristiana T.,Cheung, Chen-Yi,Hards, Kiel,Cook, Gregory M.,Stocker, Bridget L.,Timmer, Mattie S. M.
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supporting information
p. 1278 - 1285
(2019/02/24)
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- Structure-based design, synthesis and evaluation of 2,4-diaminopyrimidine derivatives as novel caspase-1 inhibitors
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Interleukin-1β converting enzyme contributes in various inflammatory and autoimmune diseases by maturing pro-inflammatory cytokines IL-1β, IL-18 and IL-33. Therefore, inhibition caspase-1 may provide a potential therapeutic strategy for the treatment of chronic inflammatory diseases. Here we have reported structure-based design, synthesis and biological evaluation of 2,4-diaminopyrimidine derivatives (6a-6w) as potential caspase-1 inhibitors. Six compounds 6m, 6n, 6o, 6p, 6q and 6r showed significant enzymatic inhibition with IC5 0 ranging from 0.022 to 0.078 μM. These compounds also displayed excellent cellular potency at sub-micromolar concentration. Moreover, molecular docking studies provided the useful binding insights specific for caspase-1 inhibition. All these results indicated that compounds 6m, 6n and 6o could be potential leads for the development of newer caspase-1 inhibitors as anti-inflammatory agents.
- Patel, Shivani,Modi, Palmi,Ranjan, Vishal,Chhabria, Mahesh
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p. 258 - 268
(2018/04/05)
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- Synthesizing method of 2-amino-4-hydroxyl-6-methylpyrimidine
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The invention relates to a synthesizing method of 2-amino-4-hydroxyl-6-methylpyrimidine. The synthesizing method comprises the following steps of (a) synthesizing of 2-methoxyl-2-ethyl butyrate: mixing ethyl acetate and a catalyst, after heating and refluxing, performing self-condensation reaction of the ethyl acetate, so as to obtain the 2-methoxyl-2-ethyl butyrate; (b) synthesizing of 2-amino-4-hydroxyl-6-methylpyrimidine; dissolving the 2-methoxyl-2-ethyl butyrate into methyl alcohol, dissolving, mixing with guanidine hydrochloride, after heating and refluxing, evaporating the residual solvent, adding deionized water until completely dissolving, using diluted hydrochloric acid to adjust the pH (potential of hydrogen) value, separating solid and filtering, spraying the solid by deionized water, obtaining the 2-amino-4-hydroxyl-6-methylpyrimidine, and drying. The synthesizing method has the advantages that the toxicity of the raw material is low, the cost is low, and the green and environment-friendly effects are realized; the traditional synthesizing method using volatile acetone with stronger toxicity or phenylboronic acid with hypertoxicity is improved, the injury to production personnels and environments is decreased, and the difficulty in production is reduced.
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Paragraph 0025; 0026; 0027; 0028; 0029; 0034-0039
(2017/10/10)
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- 9-Benzoyl 9-deazaguanines as potent xanthine oxidase inhibitors
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A novel potent xanthine oxidase inhibitor, 3-nitrobenzoyl 9-deazaguanine (LSPN451), was selected from a series of 10 synthetic derivatives. The enzymatic assays were carried out using an on-flow bidimensional liquid chromatography (2D LC) system, which allowed the screening the measurement of the kinetic inhibition constant and the characterization of the inhibition mode. This compound showed a non-competitive inhibition mechanism with more affinity for the enzyme-substrate complex than for the free enzyme, and inhibition constant of 55.1 ± 9.80 nM, about thirty times more potent than allopurinol. Further details of synthesis and enzymatic studies are presented herein.
- Rodrigues, Marili V.N.,Barbosa, Alexandre F.,Da Silva, Júlia F.,Dos Santos, Deborah A.,Vanzolini, Kenia L.,De Moraes, Marcela C.,Corrêa, Arlene G.,Cass, Quezia B.
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p. 226 - 231
(2015/12/31)
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- Discovery and SAR of 6-alkyl-2,4-diaminopyrimidines as histamine H 4 receptor antagonists
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This report discloses the discovery and SAR of a series of 6-alkyl-2-aminopyrimidine derived histamine H4 antagonists that led to the development of JNJ 39758979, which has been studied in phase II clinical trials in asthma and atopic dermatitis. Building on our SAR studies of saturated derivatives from the indole carboxamide series, typified by JNJ 7777120, and incorporating knowledge from the tricyclic pyrimidines led us to the 6-alkyl-2,4-diaminopyrimidine series. A focused medicinal chemistry effort delivered several 6-alkyl-2,4-diaminopyrimidines that behaved as antagonists at both the human and rodent H4 receptor. Further optimization led to a panel of antagonists that were profiled in animal models of inflammatory disease. On the basis of the preclinical profile and efficacy in several animal models, JNJ 39758979 was selected as a clinical candidate; however, further development was halted during phase II because of the observation of drug-induced agranulocytosis (DIAG) in two subjects.
- Savall, Brad M.,Chavez, Frank,Tays, Kevin,Dunford, Paul J.,Cowden, Jeffery M.,Hack, Michael D.,Wolin, Ronald L.,Thurmond, Robin L.,Edwards, James P.
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p. 2429 - 2439
(2014/04/17)
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- Direct synthesis of 5- and 6-substituted 2-aminopyrimidines as potential non-natural nucleobase analogues
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A series of 2-aminopyrimidine derivatives, substituted at 5- and 6-positions, were synthesized. The reaction was carried out in a single step by treatment of the corresponding β-ketoester or β-aldehydoester with guanidine hydrochloride in the presence of K2CO3, in a microwave-assisted method without the requirement of solvent. A unique 1:1 co-crystal structure was obtained which shows that a 6-phenyl-2- aminopyrimidinone forms a strong nucleobase-pair with cytosine, involving three hydrogen bonds. The base-pair was found to be as strong as that of natural guanine:cytosine (G:C), signifying the potential application of the synthesized derivatives. Additionally, we also report a second co-crystal involving 5-isopropyl-6-methyl-2-aminopyrimidinone and cytosine in a 1:1 ratio, which also shows strong base-pairing properties. the Partner Organisations 2014.
- Radhakrishnan,Sharma, Namita,Kundu, Lal Mohan
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p. 15087 - 15090
(2014/04/17)
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- Synthesis and molecular structure of 1-(Pyrimidin-2-yl)-2-(4-aryl-1,3- thiazol-2-yl)hydrazines
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Reactions of some 2-hydrazinopyrimidine hydrochlorides with potassium thiocyanate gave 1-(pyrimidin- 2-yl)thiosemicarbazides which underwent Hantzsch condensation with aryl chloromethyl ketones to produce 1-(pyrimidin-2-yl)-2-(4- aryl-1,3-thiazol-2-yl)hydrazine hydrochlorides. The protonation was accompanied by mutually dependent tautomeric rearrangements of heterocyclic fragments. Pleiades Publishing, Ltd., 2011.
- Erkin,Krutikov
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experimental part
p. 1699 - 1704
(2011/12/03)
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- SUBSTANCES FOR DYEING KERATINOUS FIBERS
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Disclosed are substances which contain unsaturated, non-aromatic dialdehydes of formula (Ia) and/or the tautomer (Ib) thereof, wherein R1, R2, and R3 are defined as indicated in claim 1, along with at least one CH-acidic compound of formulas (II) and/or (III), wherein R6, R7, R8, R9, R10, Y, X?, Het, and X1 are defined as indicated in claim 1, in a cosmetic carrier. Said substances color keratinous fibers, especially human hair, in an intensive, colorfast, natural brown shade.
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- SUBSTITUTED AMINO-PYRIMIDONES AND USES THEREOF
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This invention relates to novel compounds having the structural formula Ia or formula Ib below: (Ia,Ib), and their phatmaceutically acceptable salts, tautomers or in vivo hydrolysable precursors, compositions and methods of use thereof. These novel compounds provide a treatment or prophylaxis of Abeta related pathologies such as cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.
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(2008/06/13)
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- Preparation of pyrrole and pyrrolidine derivatives of pyrimidine. 1-(2-Pyrimidinyl)pyrrole - An inhibitor of X. Phaseoli and X. Malvacearum
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Pyrrole and pyrrolidine derivatives of pyrimidine were prepared in which the nitrogen atom of the pyrrole or pyrrolidine ring is bonded directly to the 2- or 4-carbon atom of the pyrimidine ring. Pyrrole derivatives were prepared by the dry distillation of an intimate mixture of an aminopyrimidine with mucic acid and by the reaction of a chloropyrimidine with potassium pyrrole. Pyrrolidine derivatives were prepared by the reaction of a chloropyrimidine with pyrrolidine and, in a single instance, by the catalytic hydrogenation of a pyrimidinylpyrrole. At a concentration of 200 mcg/mL, 1-(2-pyrimidinyl)pyrrole inhibited two plant pathogenic bacteria -Xanthomanus phaseoli (pathogenic on the bean plant) and Xanthomanus malvacearum (pathogenic on the cotton plant).
- Becker, Irwin
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p. 343 - 348
(2007/10/03)
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- Two-layer imageable element comprising thermally reversible polymers
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The present invention includes a two-layer imageable element, including: a substrate, a top layer including a first thermally imageable composition including (a) a first thermally sensitive supramolecular polymer or (b) a thermally imageable composition free of the first thermally sensitive supramolecular polymer; and disposed between the substrate and the top layer, a bottom layer including a second thermally imageable composition, which includes a second thermally sensitive supramolecular polymer. The present invention also includes a method of producing the imaged element.
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- Structural studies on bioactive compounds. Part 29: Palladium catalysed arylations and alkynylations of sterically hindered immunomodulatory 2-amino- 5-halo-4,6-(disubstituted)pyrimidines
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The immunological agent bropirimine 5 is a tetra-substituted pyrimidine with anticancer and interferon-inducing properties. Synthetic routes to novel 5-aryl analogues of bropirimine have been developed and their potential molecular recognition properties analysed by molecular modelling methods. Sterically challenged 2-amino-5-halo-6-phenylpyrimidin-4-ones (halo=Br or I) are poor substrates for palladium catalysed Suzuki cross-coupling reactions with benzeneboronic acid because the basic conditions of the reaction converts the amphoteric pyrimidinones to their unreactive enolic forms. Palladium-mediated reductive dehalogenation of the pyrimidinone substrates effectively competes with cross-coupling. 2-Amino-5-halo-4-methoxy-6- phenylpyrimidines can be converted to a range of 5-aryl derivatives with the 5-iodopyrimidines being the most efficient substrates. Hydrolysis of the 2- amino-5-aryl-4-methoxy-6-phenylpyrimidines affords the required pyrimidin-4- ones in high yields. Semi-empirical quantum mechanical calculations show how the nature of the 5-substituent influences the equilibrium between the 1H- and 3H-tautomeric forms, and the rotational freedom about the bond connecting the 6-phenyl group and the pyrimidine ring. Both of these factors may influence the biological properties of these compounds. (C) 2000 Elsevier Science Ltd.
- Hannah, Duncan R.,Sherer, Edward C.,Davies, Roy V.,Titman, Roger B.,Laughton, Charles A.,Stevens, Malcolm F. G.
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p. 739 - 750
(2007/10/03)
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- 3-Ethyl-6-methyl-isocytosines: Synthesis and solid state structural analysis
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The syntheses and solid state structures of 3-ethyl-6- methyl-5-alkyl-isocytosines (alkyl=H, Me, Et, n-Pr, n-Bu) are presented. These heterocycles consistently self-assemble into N-H N hydrogen-bonded dimers, which further associate by N-H···O=C interactions, or N-H···O-H···O=C hydrogen bonds involving water of crystallization, generating extended supramolecular networks. Crystal packing analysis indicates that although hydrogen bonding is the primary intermolecular interaction in these molecular crystals, the dispersion forces may play a decisive role in determining their final three-dimensional arrangements. (C) 2000 Elsevier Science Ltd.
- Custelcean, Radu,Craciun, Liliana
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p. 5067 - 5075
(2007/10/03)
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- A C-13 nuclear magnetic resonance study of the pyrimidine synthesis by the reactions of 1,3-dicarbonyl compounds with amidines and ureas
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The detailed mechanistic pathways are elucidated for the reactions of acetylacetone, methyl acetoacetate, and dimethyl malonate with a variety of amidines and ureas.In many cases the identification of a single intermediate allows the definition of the reaction path and identification of two steps.Intermediates characterized include ring-closed dihydroxytetrahydropyrimidines, dihydrohydroxypyrimidinones, open-chain enamides, and carbonyl addition compounds.
- Katritzky, Alan R.,Yousaf, Taher I.
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p. 2087 - 2093
(2007/10/02)
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- 6-ALKYL- AND 5,6-DIALKYL-2-METHOXY-4-(3H)-PYRIMIDINONES IN THE TRANSFORMATIONS OF PYRIMIDINES. CONVERSION INTO 2-SUBSTITUTED AMINO- AND 4-CHLORO-PYRIMIDINE-DERIVATIVES
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6-Alkyl- and 5,6-dialkyl-2-methoxy-4(3H)-pyrimidinones are transformed into the 2-alkyl (and 2-aryl)amino-derivatives, in good yield, by reaction with the corresponding amines.Treatment with SOCl2-DMF gives 6-alkyl- and 5,6-dialkyl-2-methoxy-4-chloropyrimidines.
- Botta, M.,Angelis, F. De,Finizia, G.,Gambacorta, A.,Nicoletti, R.
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- NOVEL RING TRANSFORMATION REACTIONS AND THEIR APPLICATIONS TO THE SYNTHESES OF POTENTIAL ANTICANCER HETEROCYCLIC COMPOUNDS
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Novel heterocyclic ring trasformation reactions developed recently in our laboratory are described.They include pyrimidine to pyrimidine, pyrimidine to pyridine transformations.Also discussed are novel one-step procedures for conversion of 1,3-dimethyluracil derivatives into the pyridopyrimidine system.Some applications of these novel reactions to the syntheses of compounds of biological interest are also described.
- Watanabe, K. A.,Su, T.-L.,Pankiewicz, K. W.,Harada, K.
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p. 289 - 307
(2007/10/02)
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- Pyrimidine to pyrimidine transformation process
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There is provided a novel process for pyrimidine to pyrimidine transformations by the displacement of the 1,2,3-portion of a pyrimidine by a 1,3-ambident nucleophile. The novel process requires that the 1 and 3 nitrogens of the pyrimidine moiety be substituted. The novel process makes available, inter alia, novel uracils, simple methods of radioisotopically labeling pyrimidine nuclei, a simple and inexpensive method of preparing the important antiviral and antileukemic material pseudoisocytidine and its new active analog 2'-deoxypseudoisocytidine.
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