Synthesis of novel pyrimidine derivatives with (pyridin-3-ylmethyl)thio and phenylamino moieties and evaluation of their antifungal activity

A series of novel pyrimidine derivatives with (pyridin-3-ylmethyl)thio and phenylamino moieties were synthesized from ethyl acetoacetate, thiourea, 3-pyridinylmethyl chloride hydrochloride, and substituted anilines by multi-step reactions. The structures of the target compounds were characterized by IR, ¹H NMR, ¹³C NMR and elemental analysis. The in vitro antifungal activities against Botrytis cinerea and Sclerotinia sclerotiorum were evaluated. The result showed that N-phenyl-6-methyl-2- ((pyridin-3-ylmethyl)thio) pyrimidin-4-amine (4a) displayed high inhibition activity against Botrytis cinerea with 87.5%inhibition at 100 µg/mL; 4a, and N-(4-isopropylphenyl)-6-methyl-2-((pyridin-3-ylmethyl)thio)pyrimidin-4-amine (4c), N-(4-methoxyphenyl)-6-methyl-2-((pyridin-3-ylmethyl)thio)pyrimidin-4-amine (4d) and N-(2-hydroxy-5-chloro)-6-methyl-2-((pyridin-3-ylmethyl)thio)pyrimidin- 4-amine (4h) exhibited sufficient activities against Sclerotinia sclerotiorum with 86.6% –93.7% inhibitions at the same concentration.     

无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应

开发了无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应.应用该反应在甲醇中回流,以39%~83%的收率合成了一系列4-(N-(2,2-二氟乙基)(N-杂环芳基甲基)氨基)-5,5-二取代呋喃-2(5H)-酮,其结构经1H NMR,13C NMR和HR-ESI-MS表征,并进一步通过3-氯-4-(N-2,2-二氟乙基)(N-嘧啶-5-基甲基胺基)-5,5-螺(4-甲氧基环己基)呋喃-2(5H)-酮(8)的晶体衍射间接证实.测试了所合成化合物的生物活性,结果表明,在600μg·mL^-1浓度时4-(N-2,2-二氟乙基)(N-6-氯吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3a)和4-(N-2,2-二.氟乙基)(N-6-氟吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3c)对桃蚜的死亡率均为100%.     

New Quinoline Derivatives on the Basis of (4-Hydroxy-2-methylquinolin-3-yl)acetic Acid

A procedure was developed for the synthesis of (4-hydroxy-2-methylquinolin-3-yl)acetic acid and the corresponding acyl chloride. Reactions of the latter with o-aminobenzenethiol, o-phenylenediamine, o-aminophenol, anthranilic acid, and thiosemicarbazide gave, respectively, 2-(4-hydroxy-2-methylquinolin-3-ylmethyl)-1,3-benzothiazole, -benzoxazole, -benzimidazole, 2-(4-hydroxy-2-methylquinolin-3-ylmethyl)-4H-3,1-benzoxazin-4-one, and 4-hydroxy-2-methyl-3-(5-sulfanyl-1H-1,2,4-triazol-3-ylmethyl)quinoline.     

A new fluorescent-colorimetric chemosensor for fluoride anion based on benzimidazolium salt

Two new benzimidazolium salts with the same cationic moiety and different anions 3-(2′-((8″-hydroxy-9″,10″-dioxo-9″,10″-dihydroanthracen-1″-yl)oxy)ethyl)-1-(pyridin-2?-ylmethyl)-1H-benzo[d]imidazol-3-ium bromide and 3-(2′-((8″-hydroxy-9″,10″-dioxo-9″,10″-dihydroanthracen-1″-yl)oxy)ethyl)-1-(pyridin-2?-ylmethyl)-1H-benzo[d]imidazol-3-ium hexafluorophosphate were prepared and characterized. The single crystal structure of 3-(2′-((8″-hydroxy-9″,10″-dioxo-9″,10″-dihydroanthracen-1″-yl)oxy)ethyl)-1-(pyridin-2?-ylmethyl)-1H-benzo[d]imidazol-3-ium bromide was determined by X-ray single crystal diffraction. Particularly, anion recognition using 3-(2′-((8″-hydroxy-9″,10″-dioxo-9″,10″-dihydroanthracen-1″-yl)oxy)ethyl)-1-(pyridin-2?-ylmethyl)-1H-benzo[d]imidazol-3-ium hexafluorophosphate as a chemosensor was carried out via fluorescence and ultraviolet spectroscopy, ¹H NMR titrations, HRMS and IR spectra. The response of this chemosensor to fluoride anion can be observed through both remarkable fluorescence quenching and color change under visible light (from orange to purple). The results indicated that this chemosensor can distinguish fluoride anion from other anions via the instrument and naked eyes, and this is greatly convenient in practical operation.     

Rhenium tricarbonyl core complexes of thymidine and uridine derivatives

Thymidine and uridine were modified at the C2' and C5' ribose positions to form amine analogues of the nucleosides (1 and 4). Direct amination with NaBH(OAc)3 in DCE with the appropriate aldehydes yielded 1-{5-[(bis(pyridin-2-ylmethyl)amino)methyl]-4-hydroxytetrahydrofuran-2-yl}-5-methyl-1H-pyrimidine-2,4-dione (L1), 1-{5-[(bis(quinolin-2-ylmethyl)amino)methyl]-4-hydroxytetrahydrofuran-2-yl}-5-methyl-1H-pyrimidine-2,4-dione (L2), and 1-[3-(bis(pyridin-2-ylmethyl)amino)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidine-2,4-dione (L5), while standard coupling procedures of 1 and 4 with 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid (2) and 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid (3) in the presence of HOBT-EDCI in DMF provided a second novel series of bifunctional chelators: 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid [(3-hydroxy-5-(5-methyl-4-oxo-3,4-dihydro-2H-pyrimidin-1-yl)tetrahydrofuran-2-yl)methyl] amide (L3), 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid [(3-hydroxy-5-(5-methyl-4-oxo-3,4-dihydro-2H-pyrimidin-1-yl)tetrahydrofuran-2-yl)methyl] amide (L4), 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid [2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-3-yl] amide (L6), and 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid [2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-3-yl] amide (L7). The rhenium tricarbonyl complexes of L1-L4, L6, and L7, [Re(CO)3(LX)]Br (X=1-4, 6, 7: compounds 5-10, respectively), have been prepared by reacting the appropriate ligand with [NEt4][Re(CO)3Br3] in methanol. The ligands and their rhenium complexes were obtained in good yields and characterized by common spectroscopic techniques including 1D and 2D NMR, HRMS, IR, cyclic voltammetry, UV, and luminescence spectroscopy and X-ray crystallography. The crystal structure of complex 6.0.5NaPF6 displays a facial geometry of the carbonyl ligands. The nitrogen donors of the tridentate ligand complete the distorted octahedral spheres of the complex. Crystal data: monoclinic, C2, a = 24.618(3) A, b = 11.4787(11) A, c = 15.5902(15) A, beta = 112.422(4) degrees , Z = 4, D(calc) = 1.562 g/cm3.     

Spontaneous cyclization of (acridin-9-ylmethyl)thioureas to spiro [dihydroacridine-9′(10′H),5-imidazolidine]-2-thiones,a novel type of acridine spirocycles

Novel acridine spirocompounds, spiro[dihydroacridine-9′(10′H),5-imidazolidine]-2-thiones have been prepared by the spontaneous cyclization of 1-substituted 3-(acridin-9-ylmethyl)thioureas, which were obtained from 1-(acridin-9-yl)methanamine, N-(acridin-9-ylmethyl)propan-1-amine, and N-(acridin-9-ylmethyl)benzylamine and alkyl/aryl isothiocyanates, as continuation of our previous studies on new acridine spirocycles. Imidazolidine-2-thiones thus obtained were subsequently transformed with mesitylnitrile oxide to imidazolidine-2-one analogues, some of which partly reopened to the corresponding (acridin-9-ylmethyl)ureas. An unusual spirocyclization via a CH carbanion instead of the N-1 nitrogen has been found for 3-(acridin-9-ylmethyl)-1-(acridin-9-yl)thioureas possessing two acridine rings. Structural modifications in positions 1, 3, and 4 of the spiro ring together with ¹H, ¹³C, and ¹⁵N NMR spectroscopy and X-ray crystallography have been employed to rationalize a general propensity of various 9-substituted acridines to undergo easy spirocyclization.     

2,6,7-Trihydroxy-4,9-dioxodeca-2,5,7-trienoic and 2-hydroxy-2-(3-hydroxy-4-methyl-2,5-dioxocyclopent-3-en-1-ylidene)acetic acid esters: Synthesis and structural specificity

Claisen condensation of acetone and butan-2-one with diethyl oxalate in the presence of metallic sodium leads to the formation of ethyl 2,6,7-trihydroxy-4,9-dioxodeca-2,5,7-trienoate and ethyl 2-hydroxy-2-(3-hydroxy-4-methyl-2,5-dioxocyclopent-3-en-1-ylidene)acetate, respectively.     

Intercalating nucleic acids (INAs) with insertion of N-(pyren-1-ylmethyl)-(3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol. DNA (RNA) duplex and DNA three-way junction stabilities

N-(Pyren-1-ylmethyl)-(3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol was synthesised from (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol and (3R,4S)-4-[(1S)-1,2-dihydroxyethyl] pyrrolidin-3-ol using alkylation with 1-(chloromethyl)pyrene or reductive amination with pyrene-1-carbaldehyde and NaCNBH3. The incorporation of N-(pyren-1-ylmethyl)azasugar moiety into oligodeoxynucleotides (ODN) as a bulge to form an intercalating nucleic acid (INA) induced a slight destabilization of INA-DNA duplex, whereas the INA-RNA duplex was strongly destabilized and 9 degrees C difference per modification in thermal stability between INA-DNA over INA-RNA duplexes was observed. The stabilization of a DNA three way junction (TWJ) was improved when the intercalator moiety was inserted into the junction region as a bulge.     

Synthesis of Diazadi(and tri)thiacrown Ethers Containing Two 5-Substituent(or 2-methyl)-8-hydroxyquinoline Side Arms

Abstract

Sixteen new diazadi(or tri)thiacrown ethers containing two 5-substituent(or 2-methyl)-8-hydroxyquino-lin-2-ylmethyl side arms have been prepared by a three-step process. First, the appropriate bis(α-chloroamide)s were treated with five dimercaptans in base to form macrocyclic di(or tri)thiadiamides. The macrocyclic diamides were reduced by BH₃-THF to form 1,7-diaza-4-oxa-10,13-dithia-cyclopentadecane (11); 1,7-diaza-4,13-dioxa-10,16-dithiacyclooctadecane (12); 1,7-diaza-4-oxa-10,13,16-trithiacyclooctadecane (13); 1,7-diaza-4,13,16-trioxa-10,19-dithiacycloheneicosane (14); and 1,10-diaza-4,7-dioxa-13,16-dithiacyclooctadecane (15). The diazadi(or tri)thiacrown ethers were then treated with 8-hydroxyquinoline, 8-hydroxy-5-methylquinoline, 5-chloro-8-hydroxyquinoline, and 8-hydroxyquinaldine in the presence of paraformal-delyde in refluxing benzene to form the bis(8-hydroxy-5-substituent(or 2-methyl)quinolin-7-ymethy)-substituted diazadi(or tri)thiacrown ethers 16-31. The crown ethers containing two 8-hydroxyquinoline or 8-hydroxyquinaldine side arms proved to be mixtures of about 90% bis(8-hydroxyquinolin-7-ylmethyl)-substituted crown ethers; 9% mixed (8-hydroxyquinolin-7-ymethyl)-substituted and (8-hydroxyquinolin-5-ylmethyl)-substituted crown ethers; and 1% bis(8-hydroxyquinolin-5-ylmethyl)-substituted crown ethers.     

Midrange affinity fluorescent Zn(II) sensors of the Zinpyr family: syntheses, characterization, and biological imaging applications

The syntheses and photophysical characterization of ZP9, 2-{2-chloro-6-hydroxy-3-oxo-5-[(2-{[pyridin-2-ylmethyl-(1H-pyrrol-2-ylmethyl)amino]methyl}phenylamino)methyl]-3H-xanthen-9-yl}benzoic acid, and ZP10, 2-{2-chloro-6-hydroxy-5-[(2-{[(1-methyl-1H-pyrrol-2-ylmethyl)pyridin-2-ylmethylamino]methyl}phenylamino)methyl]-3-oxo-3H-xanthen-9-yl}benzoic acid, two asymmetrically derivatized fluorescein-based dyes, are described. These sensors each contain an aniline-based ligand moiety functionalized with a pyridyl-amine-pyrrole group and have dissociation constants for Zn(II) in the sub-micromolar (ZP9) and low-micromolar (ZP10) range, which we define as "midrange". They give approximately 12- (ZP9) and approximately 7-fold (ZP10) fluorescence turn-on immediately following Zn(II) addition at neutral pH and exhibit improved selectivity for Zn(II) compared to the di-(2-picolyl)amine-based Zinpyr (ZP) sensors. Confocal microscopy studies indicate that such asymmetrical fluorescein-based probes are cell permeable and Zn(II) responsive in vivo.     

Synthesis of N-cycloalkenylazoles

N-(1-Cycloalkenyl)pyrroles 3a,b, -pyrazoles 6a,b, and -imidazoles 9a,b were synthesized via elimination of benzotriazole or 5-phenyltetrazole from the corresponding 1-[1-(heterocycyl)cycloalkyl]benzotriazoles 2, 5, and 8 or 1-[1-(heterocycyl)cyclohexyl]-5-phenyltetrazole (12 and 14). Intermediates 2, 5, 8, 12 and 14 were obtained by cyclizations of dihaloalkanes with N-(benzotriazol-1-ylmethyl)heterocycles, 1-imidazol-1-ylmethyl-5-phenyltetrazole (11), or 1-pyrazol-1-ylmethyl-5-phenyltetrazole (13) in the presence of n-BuLi.     

Synthesis and studies of biological activity of N-(4-tert-butylbenzyl)-N-(pyridin-3-ylmethyl)-2-aminothiazolines as potential multifunctional agents for treatment of neurodegenerative diseases

Russian Chemical Bulletin - A number of N-(4-tert-butylbenzyl)-N-(pyridin-3-ylmethyl)-2-aminothiazolines with different substituents at position 5 of thiazoline ring was synthesized and their...     

C-hydroxyalkylation of N-adamantylanilines by hexafluoroacetone and methyl trifluoropyruvate

N-(1-Adamantyl)-4-(1-hydroxy-1-trifluoromethyl- 2,2,2- trifluoroethyl)aniline (III) and N-(1-adamantyl)-4-(1-hydroxy-1-methoxycarbony 1-2,2,2-trif luoroethyl) aniline (IV) were obtained by the reaction of N-(1-adamantyl)aniline with ketone (I) and ketoester (II). Analogous procedures gave N-(2-adamantyl)- 4- (1-hydroxy- 1-trifluoromethyl- 2, 2,2-trifluoroethyl)aniline (V) and N-(2-adamantyl)-4-(1-hydroxy-1-methoxycarbonyl-2,2,2-trifluoroethyl)aniline (VI). The action of hydrogen peroxide on (III) in the presence of sodium tungstenate gave N- (1- adamantyl)- 4- (1- hydroxy- 1- trifluoromethyl- 2,2,2- trifluoroethyl)aniline N-oxide (VII).Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2348–2350, October, 1989.     

Biomimetic iron(III) complexes of N3O and N3O2 donor ligands: protonation of coordinated ethanolate donor enhances dioxygenase activity

A series of iron(III) complexes 1-4 of the tripodal tetradentate ligands N,N-bis(pyrid-2-ylmethyl)-N-(2-hydroxyethyl)amine H(L1), N,N-bis(pyrid-2-ylmethyl)-N-(2-hydroxy- propyl)amine H(L2), N,N-bis(pyrid-2-ylmethyl)-N-ethoxyethanolamine H(L3), and N-((pyrid-2-ylmethyl)(1-methylimidazol-2-ylmethyl))-N-(2-hydroxyethyl)amine H(L4), have been isolated, characterized and studied as functional models for intradiol-cleaving catechol dioxygenases. In the X-ray crystal structure of [Fe(L1)Cl(2)] 1, the tertiary amine nitrogen and two pyridine nitrogen atoms of H(L1) are coordinated meridionally to iron(III) and the deprotonated ethanolate oxygen is coordinated axially. In contrast, [Fe(HL3)Cl(3)] 3 contains the tertiary amine nitrogen and two pyridine nitrogen atoms coordinated facially to iron(III) with the ligand ethoxyethanol moiety remaining uncoordinated. The X-ray structure of the bis(μ-alkoxo) dimer [{Fe(L5)Cl}(2)](ClO(4))(2)5, where HL is the tetradentate N(3)O donor ligand N,N-bis(1-methylimidazol-2-ylmethyl)-N-(2-hydroxyethyl)amine H(L5), contains the ethanolate oxygen donors coordinated to iron(III). Interestingly, the [Fe(HL)(DBC)](+) and [Fe(HL3)(HDBC)X] adducts, generated by adding ～1 equivalent of piperidine to solutions containing equimolar quantities of iron(III) complexes 1-5 and H(2)DBC (3,5-di-tert-butylcatechol), display two DBC(2-)→ iron(III) LMCT bands (λ(max): 1, 577, 905; 2, 575,915; 3, 586, 920; 4, 563, 870; 5, 557, 856 nm; Δλ(max), 299-340 nm); however, the bands are blue-shifted (λ(max): 1, 443, 700; 2, 425, 702; 3, 424, 684; 4, 431, 687; 5, 434, 685 nm; Δλ(max), 251-277 nm) on adding 1 more equivalent of piperidine to form the adducts [Fe(L)(DBC)] and [Fe(HL3)(HDBC)X]. Electronic spectral and pH-metric titration studies in methanol disclose that the ligand in [Fe(HL)(DBC)](+) is protonated. The [Fe(L)(DBC)] adducts of iron(III) complexes of bis(pyridyl)-based ligands (1,2) afford higher amounts of intradiol-cleavage products, whereas those of mono/bis(imidazole)-based ligands (4,5) yield mainly the auto-oxidation product benzoquinone. It is remarkable that the adducts [Fe(HL)(DBC)](+)/[Fe(HL3)(DBC)X] exhibit higher rates of oxygenation affording larger amounts of intradiol-cleavage products and lower amounts of benzoquinone.     

Cu(II), Ni(II) and Fe(II) complexes with a new substituted [1,2,4] triazole Schiff base derived from 4-amino-5-(thien-2-yl ethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one and 2-hydroxy-1-naphthaldehyde: synthesis,characterization and a comparison of theoretical and experimental results by Ab inito calculation

The synthesis and structural properties of two novel compounds, 4-amino-5-(thien-2-yl ethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one and 4-{[(2-hydroxy-1-naphthyl)methyl-ene]amino}-5-(thien-2-ylmethyl) − 2,4-dihydro-3H-1,2,4-triazol-3-one have been described. 4-Amino-5-(thien-2-ylmethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one was synthesized by treating N-propionyl-2-thien-2-ylethane-hydrazonoate with hydrazine hydrate and the Schiff base was obtained from condensation of substituted amine with 2-hydroxy-1-naphthaldehyde. The Cu(II), Ni(II) and Fe(II) complexes were prepared and characterized by elemental analyses, IR, magnetic moment, UV–Vis, mass spectral data and ¹H- and ¹³C-NMR IR spectra. The Schiff base is coordinated to the metal ions in a tridentate manner with OON donors of the phenolic O, carbonyl O and triazolic N. From the magnetic and UV spectral data, it was found the geometrical structure of Cu(II) and Fe(II) ions are octahedral while Ni(II) ion is square planar.Ab-inito 6-31 G* level calculations provided structural information and IR data that were in good agreement with experimental results.     

Synthesis of potential biologically active 1,2-benzothiazin-3-yl-quinazolin-4(3H)-ones

A series of potential biologically active 2-(4-hydroxy-1,1-dioxido-2H-1,2-benzothiazin-3-yl)quinazolin-4(3H)-ones was synthesized in a straight forward manner by condensation of respective 4-hydroxy-1,2-benzothiazine-1,1-dioxides with anthranilamide followed by simple and high throughput cyclization of N-[2-(aminocarbonyl)phenyl]-4-hydroxy-1,2-benzothiazine-3-carboxamide-1,1-dioxides. All the synthesized compounds were subjected to preliminary evaluation for their biological activity against Gram positive and Gram negative bacteria. Some of the assayed compounds showed marked activity against Bacillus subtilis.     

Synthesis and properties of sym-triazines. 10 Synthesis of 2,4-diamino-sym-triazines containing a sterically hindered phenol substituent

Condensation of N-(4-hydroxy-3,5-di-tert-butylphenyl)biguanide with esters in the presence of catalytic amounts of sodium ethylate gives 2-amino-4-(4-hydroxy-3,5-di-tert-butylanilino)-6-substituted sym-triazines. When the trichloroacetate ester is used the main product is 2-amino-4-(4-hydroxy-3,5-di-tert-butylanilino)-6-oxo-1(5)H-sym-triazine.For communication 9 see [1]Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1395–1399, October, 1992.     

Synthesis of new <Emphasis Type="Italic">N</Emphasis>-(pyridin-3-ylmethyl)-2-aminothiazoline derivatives possessing anticholinesterase and antiradical activity as potential multifunctional agents for the treatment of neurodegenerative diseases

New N-(pyridin-3-ylmethyl)-2-aminothiazolines containing various substituents at the 5 position of the thiazoline ring and the 4-tert-butylbenzyl, 4-isopropylbenzyl, or 4-fluorobenzyl moiety at the nitrogen atom of the amino group were synthesized. The inhibitory activity of the synthesized compounds against human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7), equine serum butyrylcholinesterase (BChE, EC 3.1.1.8), and porcine liver carboxylesterase (CaE, EC 3.1.1.1) was evaluated and their antioxidant properties were studied by ABTS assay. N-(Pyridin-3-ylmethyl)-2-aminothiazolines proveded to be very weak AChE inhibitors, while their inhibitory activity against BChE and CaE was structure-dependent. 2-Aminothiazolines containing the 4-tert-butylbenzyl moiety are more efficient BChE inhibitors compared to the derivatives containing the 4-isopropylbenzyl or 4-fluorobenzyl substituent. An analysis of the dependence of the esterase profile of N-(pyridin-3-ylmethyl)-2-aminothiazolines on the structure of the substituent at the 5 position of the thiazoline ring of these compounds demonstrated that the derivatives containing the iodomethyl substituent possess the highest anti-BChE activity, the compounds with R² = H and R³ = CH₂I have the optimal esterase profile. Regardless of the structure of the substituents in the benzyl moiety, all N-(pyridin-3-ylmethyl)-2-aminothiazolines containing the iodomethyl substituent at the 5 position of the thiazoline ring exhibited high radical scavenging activity comparable with that of the standard antioxidant Trolox. N-(Pyridin-3-ylmethyl)-2-aminothiazolines were shown to be a new promising class of compounds for the design of multifunctional agents for the treatment of neurodegenerative diseases.     

Comparison of the isolation of adducts of 2'-deoxycytidine and 2'-deoxyguanosine with phenylglycidyl ether by high-performance liquid chromatography on a reversed-phase column and a polystyrene-divinylbenzene column

2'-Deoxycitidine (dCyd) and 2'-deoxyguanosine (dGuo) were subjected to reaction with phenylglycidyl ether (PGE) in methanol in order to study the formation of the corresponding 2'-deoxynucleoside adducts. Separation methods were developed on analytical and semi-preparative scales using high-performance liquid chromatography with photodiode-array detection on a reversed-phase column and on a polystyrene-divinylbenzene column. The use of the latter column was prompted by decomposition of the preparatively isolated dGuo-PGE adducts on the reversed-phase column. The use of a polystyrene-divinylbenzene column solved this problem and also revealed the presence of one more peak in both the dCyd- and dGuo-PGE reaction mixtures. The adducts of dCyd and dGuo were isolated on preparative reversed-phase and polystyrene-divinylbenzene columns and characterized by UV, fast atom bombardment mass and 360 MHz 1H NMR spectrometry. The adducts of dCyd were the diastereomers of N-3-(2-hydroxy-3-phenoxypropyl)-2'-deoxycytidine and N4-(2-hydroxy-3-phenoxypropyl)-2'-deoxycytidine whereas those of dGuo were the two diastereomers of N-7-(2-hydroxy-3-phenoxypropyl)-2'-deoxyguanosine and a third peak which appeared to be mainly N2-(2-hydroxy-3-phenoxypropyl)-2'-deoxyguanosine.     

Reaction of 4-aryl-2-hydroxy-4-oxo-2-butenoic acid <Emphasis Type="Italic">N</Emphasis>-(4-acetylaminosulfonylphenyl)amides with hydrazine hydrate and phenylhydrazine

Reaction of 4-aryl-2-hydroxy-4-oxo-2-butenoic acid N-(4-acetylaminosulfonylphenyl)amides with hydrazine hydrate and phenylhydrazine in acetic acid has afforded N-[4-(acetylaminosulfonyl)phenyl]-5-arylpyrazole-3-carboxamides.