Synthesis and bioactivity of 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-xylopyranosyl-1,3,4-oxa(thia)diazol-2-amines

A series of new N′-[N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)thiocarbamoyl]-2-[(1-aryl-1H-tetrazol-5-yl)sulfanyl]acetohydrazides 5a–5e were synthesized rapidly in high yields from 2-(1-aryl-1H-tetrazol-5-ylsulfanyl)acetohydrazides 3a–3e and 2,3,4-tri-O-acetyl-β-d-xylopyranosyl isothiocyanate 4, then 5a–5e were converted to a series of new 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)-1,3,4-oxadiazole-2-amines 6a–6e and 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)-1,3,4-thiadiazole-2-amines 7a–7e, respectively under mercuric acetate/alcohol system or acetic anhydride/phosphoric acid system, then deacetylated in the solution of CH₃ONa/CH₃OH. All of the novel compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS and elemental analysis. The structures of compounds 2e, 3e, 5a and 5c have been determined by X-ray diffraction analysis. Some of the synthesized compounds displayed PTP1B inhibition and microorganism inhibition.     

Syntheses of 1-[(2-Hydroxyethoxy)methyl]- and 1-[(1,3-Dihydroxy-2-Propoxy)methyl]- Derivatives of 5-Substituted-2,4-difluorobenzene: Unnatural Acyclo Thymidine Mimics for Evaluation as Anticancer and Antiviral Agents

Abstract

A group of 1-[(2-hydroxyethoxy)methyl]- (12) and 1-[(1,3-dihydroxy-2-propoxy)methyl]- (13) derivatives of 2,4-difluorobenzene possessing a variety of C-5 substituents (R = Me, H, I, NO₂) were designed with the expectation that they may serve as acyclic 5-substituted-2′-deoxyuridine (thymidine) mimics. Compounds 12 and 13 (R = Me, H, I) were inactive as anticancer agents (C₅₀ = 10^?3 to 10^?4 M range), whereas the 5-nitro compounds (12d, 13d) exhibited weak-to-moderate cytotoxicity (CC₅₀ = 10^?5 to 10^?6 M range) against a variety of cancer cell lines. All compounds prepared (12a-d, 13a-d) were inactive as antiviral agents in a broad-spectrum antiviral screen that also included the human immunodeficiency virus (HIV-1 and HIV-2) and herpes simplex virus (HSV-1 and HSV-2).     

Biosynthesis of Resorcylic Acid Lactone (5S)-5-Hydroxylasiodiplodin in Lasiodiplodia theobromae

An administration study of ²H-labeled precursors showed that the 9-hydroxydecanoyl unit, the acyl intermediate of lasiodiplodin (1), was also the intermediate of (5S)-5-hydroxylasiodiplodin (2) in Lasiodiplodia theobromae. The incorporation of [O-methyl-²H₃]-lasiodiplodin (6) into 2 indicated that hydroxylation at C-5 occurred after cyclization.     

Synthesis of AZT analogues: 7-(3-azido-2hydroxypropyl)-, 7-(3-amino-2-hydroxypropyl)-, 7-(3-triazolyl-2-hydroxypropyl)theophyllines

Nucleophilic displacement of the tosyloxy group in 7-(2-hydroxy-3-p-toluenesulfonyloxypropyl)theophylline (1) with azide anion afforded 7-(3-azido-2-hydroxypropyl)theophylline (2). Reduction of the 3-azido group in 2 with Ph₃P/Py/NH₄OH afforded the 3-amino derivative 4, alternatively obtained by regioselective amination of 7-(2,3-epoxypropyl)theophylline (3). Selective acetylation of 4 gave the N-acetyl derivative 5. 1,3-Dipolar cycloaddition of the azide group in 2 with N¹-propargyl thymine (6) afforded the regioisomeric triazole 7.     

Synthesis,Antitumor, and DNA Binding Behavior of Novel 4-(2-Hydroxyquinolin-3-yl)-6-Phenyl-5, 6 Dihydropyrimidin Derivatives in Aqueous Medium

This article deals with the synthesis of 4-(2-hydroxyquinolin-3-yl)-6-phenyl-5,6-dihydropyrimidin derivatives (2a–f), on condensation with various aromatic aldehydes and ketones in aqueous ethanolic NaOH solution yielding the corresponding chalcones (3). These chalcones were further reacted with thiourea/urea in the presence of a base, which led to the formation of the titled derivatives (2a–f). The newly synthesized heterocyles were characterized by elemental analysis, FTIR, ¹HNMR, and electronic and mass spectral data. The compounds (2a and 2b) were evulated for in vitro cyctotoxicity against human breast adenocarcinoma cell (MCF-7). In MTT cytotoxicity studies, both quinolinde derivatives were found most effective. The binding interaction behavior of the compound (2a) and (2d) with calf thymus-DNA (CT-DNA) was studied by electronic spectra, viscosity measurements, and thermal denaturation studies. On binding to CT-DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. The binding constant (K_b) observed 4.3 × 10⁵ M^?1 for (2a), and 3.8 × 10⁵ M^?1 for (2d) suggested that compound (2a) binds more strongly with base pairs than (2d).     

Rhodium(III) and iridium(III) complexes with 1,2-naphthoquinone-1-oximate as a bidentate ligand: synthesis,structure, and biological activity

The synthesis and characterization of three novel iridium(III) complexes and one rhodium(III) complex with 1-nitroso-2-naphthol (3) chelating as a 1,2-naphthoquinone-1-oximato ligand are described. The reaction of μ₂-halogenido-bridged dimers [(η⁵-C₅Me₅)IrX₂]₂ [X is Cl (1a), Br (1b), I (1c)] and [(η⁵-C₅Me₅)RhCl₂]₂ (2a) with 3 in CH₂Cl₂ yields the mononuclear complexes (η⁵-C₅Me₅)IrX(η²-C₁₀H₆N₂O) (4a, 4b, 4c) and (η⁵-C₅Me₅)RhCl(η²-C₁₀H₆N₂O) (5a). All compounds were characterized by their ¹H and ¹³C NMR, IR, and mass spectra, UV/vis spectra were recorded for 4a and 5a. The X-ray structure analyses revealed a pseudo-octahedral “piano-stool” configuration for the metals with bidentate coordination through oximato-N and naphthoquinone-O, forming a nearly planar five-membered metallacycle. The metal complexes 4a and 5a were evaluated in respect to their cytotoxicity and binding affinity toward double-stranded DNA. As determined in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, both exerted a much stronger cytotoxic effect toward HeLa and HL60 cancer cell lines than did cisplatin. The remarkable cytotoxicity of the compounds tested may be attributed to necrosis, rather than to apoptosis, as it is evidenced by the caspase-3/7 activation assay. No clear evidence was found for interaction with double-stranded DNA. The melting experiments showed no significant differences between thermodynamic parameters of intact DNA and DNA incubated with 3, 4a, or 5a, although these derivatives altered DNA recognition by the BamHI restriction enzyme. Therefore, the screened iridium and rhodium complexes 4a and 5a may still be interesting as potential anticancer drugs owing to their high cytotoxicity toward cancer cell lines, whereas they do not modify DNA in a way similar to that of cisplatin.     

Synthesis of l-(4-2H)erythrose,l-)1-13C, 5-2H)arabinose and l-(2-13C, 5-2H)arabinose and identification of the intermediates by 2H and 13C-N.M.R. spectroscopy

l-(1-¹³C, 5-²H)Arabinose (6D) and l-(2-¹³C, 5-²H)arabinose (8D) have been synthesized by degradation of 2,3-O-isopropylidene-α-l-rhamnofuranose (2) to l-(4-²H)erythrose (5β,5αD), with subsequent chain elongation to 6D plus l-(1-¹³C, 5-²H)ribose (7D), the latter being converted into 8D. Intermediates were identified by complete assignment of the ¹³C chemical shifts employing carbon-carbon and carbon-deuterium coupling constants, deuteration shifts, differential isotope-shifts, and deuterium spectra. The anomeric carbon atoms of 2 and 2,3-O-isopropylidene-l-(1-²H) erythrose (4D) gave only single ¹³C resonances, suggesting that these two compounds exists in only one major anomeric configuration, clarifying previously reported work. The synthesis of 2,3-O-isopropylidene-l-(1-²H)rhmanitol (3D) facilitated the assignment of the signals in the ¹³C spectra of the nondeuterated analog. Specific deuterium-enrichment and the observed carbon-deuterium coupling (¹J_C,D ∼22 Hz) not only served to identify the deuterated carbon atom unambiguously in 3 but also permitted assignment of closely spaced resonances. The deuterium spectrum of 2,3-O-isopropylidene-l-(1-²H)erythrofuranose (4D) showed only a single resonance, indicating preponderance of one anomer, in accord with the observation of a single C-1 resonance in the ¹³C spectrum.     

Synthesis, crystal structures, cytotoxicity and qualitative structure-activity relationship (QSAR) of cis-bis{5-[(E)-2-(aryl)-1-diazenyl]quinolinolato}di-n-butyltin(IV) complexes, (n)Bu2Sn(L)2

A series of cis-bis{5-[(E)-2-(aryl)-1-diazenyl]quinolinolato}di-n-butyltin(IV) complexes has been synthesized and characterized by ¹H-, ¹³C-, ¹¹⁹Sn NMR, ESI-MS (electrospray ionization mass spectrometry), IR and ^119mSn Mössbauer spectroscopic techniques in combination with elemental analyses. The structures of four di-n-butyltin(IV) complexes, viz., ⁿBu₂Sn(L³)₂ (3), ⁿBu₂Sn(L⁴)₂ (4), ⁿBu₂Sn(L⁵)₂ (5) and ⁿBu₂Sn(L⁷)₂ · 0.5C₆H₆ (7) (LH = 5-[(E)-2-(aryl)-1-diazenyl)quinolin-8-ol) were determined by single crystal X-ray diffraction. In general, the complexes were found to adopt a distorted cis-octahedral arrangement around the tin atom. These complexes retain their solid-state structure in non-coordinating solvent as evidenced by ¹¹⁹Sn and ¹³C NMR spectroscopic results. The in vitro cytotoxicity of di-n-butyltin(IV) complexes (3-8) is reported against seven well characterized human tumour cell lines. The basicity of the two quinolinolato donor N and O atoms of the ligands are discussed in relation to the cytotoxicity data.     

Novel Pt(II) and Pt(IV) complexes with 3-amino-5-methyl-5-(4-pyridyl)-2,4-imidazolidenedione. Synthesis, physicochemical, chemometric and pharmacological investigation

Platinum(II) and platinum(IV) complexes with 3-amino-5-methyl-5-(4-pyridyl)-2,4-imidazolidenedione (L) with general formulaе cis-[PtL₂X₂]·nH₂O and [PtL₂Cl₄], where X = Cl⁻, Br⁻, I⁻ and n = 2-4) were synthesized. The novel compounds were fully characterized by elemental analysis, IR, ¹H, ¹³C, ¹⁹⁵Pt NMR spectra, thermal analysis and molar conductivity. The geometry of Pt(II) complexes and of the organic ligand in the gas phase were optimized using the hybrid DFT method B3LYP with LANL2DZ and 6-31G** basis sets. Some physicochemical parameters as dipole moment, HOMO, LUMO energies and ESP charges were calculated. The comparison of the bond length and angles, obtained from the X-ray analysis and DFT calculations is realized. The cytotoxic effects of these complexes in human T-cell leukemia KE-37 (SKW-3) are reported.     

Synthesis and biological evaluation of tricarbonyl Re(I) and Tc(I) complexes anchored by poly(azolyl)borates: application on the design of radiopharmaceuticals for the targeting of 5-HT<Subscript>1A</Subscript> receptors

The building blocks fac-[^99mTc{κ³-HB(tim^Me)₃}(CO)₃] and fac-[^99mTc{κ³-R(μ-H)B(tim^Me)₂}(CO)₃] [R is H (4a), Ph (5a); tim^Me is 2-mercapto-1-methylimidazolyl] were obtained almost quantitatively by reacting fac-[^99mTc(CO)₃(H₂O)₃]⁺ with the corresponding scorpionate. These compounds cross the intact blood–brain barrier in mice, with significant retention in the case of 4a and 5a. Using 4a as the lead structure, we have synthesized the functionalized complexes fac-[M{κ³-H(μ-H)B(tim^Bu-pip)₂}(CO)₃] [M is Re (8), ^99mTc (8a); tim^Bu-pip is methyl[4-((2-methoxyphenyl)-1-piperazinyl)butyl](2-mercapto-1-methylimidazol-5-yl)methanamide] and fac-[M{κ ³-H(μ-H)B(tim^Me)(tim^Bu-pip)}(CO)₃] [M is Re (9), ^99mTc (9a)] and evaluated their potential as radioactive probes for the targeting of brain 5-HT_1A serotonergic receptors. The Re complexes exhibit excellent affinity [IC₅₀=0.172 ± 0.003 nM (8); IC₅₀=0.65 ± 0.01 nM (9)] for the 5-HT_1A receptor. The radioactive congeners (^99mTc) have shown an initial brain uptake of 1.38 ± 0.46%ID g⁻¹ (8a) and 0.43 ± 0.12%ID g⁻¹ (9a), but suffer from a relatively fast washout.     

Design and synthesis of (5-amino-1, 2, 4-triazin-6-yl)(2-(benzo[d] isoxazol-3-yl) pyrrolidin-1-yl)methanone derivatives as sodium channel blocker and anticonvulsant agents

Abstract

A series of novel (5-amino-3-substituted-1, 2, 4-triazin-6-yl) (2-(6-halo-substituted benzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5a–5r was synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test and neurotoxicity was evaluated by the rotorod test. The MES test showed that (5-amino-3-phenyl-1, 2, 4-triazin-6-yl)(2-(6-fluorobenzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5c was found to be the most potent compound with ED₅₀ value of 6.20?mg/kg (oral/rat) and a protective index (PI?=?ED₅₀/TD₅₀) value of >48.38, which was much higher than the PI of the reference drug phenytoin. To explain the possible mechanism of action of selected derivatives 5b, 5c, 5i and 5o, their influence on sodium channel was evaluated in vitro.     

Designing,synthesis and bioactivities of 4-[3-(4-hydroxyphenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]benzenesulfonamides

In this study, 4-[3-(4-hydroxyphenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]benzenesulfonamide (1–9) types compounds were synthesized and their chemical structures were confirmed by ¹H NMR, ¹³C NMR and HRMS spectra. Cytotoxic and carbonic anhydrase (CA) inhibitory effects of the compounds were investigated. Cytotoxicity experiments pointed out that compound 4, (4-[5-(4-chlorophenyl)-3-(4-hydroxyphenyl)-4,5-dihydro-pyrazol-1-yl]benzenesulfonamide), exerting the highest tumor selectivity (TS) and potency selectivity expression (PSE) values, can be considered as a lead compound of this study in terms of development of novel anticancer agents. All synthesized sulfonamides showed a good inhibition profile on hCA IX and XII in the range of 53.5–923?nM and 6.2–95?nM, respectively. These compounds were 2.5–13.4 times more selective for the inhibition of hCA XII versus hCA IX, except compound 2 which had similar inhibitory action towards both isoenzymes.     

N5-(l-1-Carboxyethyl)-l-ornithine: NADP+ oxidoreductase inStreptococcus lactis: Distribution,constitutivity, and regulation

N⁵-(l-1-Carboxyethyl)-l-ornithine: NADP⁺ oxidoreductase [N⁵-(CE)ornithine synthase] catalyzes the NADPH-dependent reductive condensation between pyruvic acid and the terminal amino group ofl-ornithine andl-lysine to yield N⁵-(l-1-carboxyethyl)-l-ornithine and N⁶-(l-1-carboxyethyl)-l-lysine respectively. Polyclonal antibodies against N⁵-(CE)ornithine synthase purified fromStreptococcus lactis K1 have been used for the immunochemical (Western blot) detection and sizing of this enzyme in various lactic acid bacteria. The enzyme was confined to about one-half of the strains ofS. lactis examined. N⁵-(CE)ornithine synthase is constitutive, and in strains K1, 6F3, and (plasmid-free)H₁-4125 the native enzyme is a tetramer composed of identical subunits of M_r=38,000. However, in other strains, including 133 (ATCC 11454), C₁₀, and ML₈, the molecular weight of the native enzyme is approximately 130,000 and the corresponding subunit M_r=35,000. Analyses of the amino acid pool components maintained byS. lactis K1 during growth in medium containing [¹⁴C] labeled and unlabeled arginine have revealed that (i) exogenous arginine is the precursor of intracellular ornithine, citrulline, and N⁵-(CE)ornithine, and (ii) the rates of turnover of ornithine and citrulline were considerably faster than that of N⁵-(CE)ornithine. These data account for the biosynthesis and accumulation of N⁵-(CE)ornithine byS. lactis.     

Evolution of 1, 3, 5-trisubstituted bipyrazole scaffold based platinum(II) complexes as a biological active agent

Abstract

Square planar mononuclear platinum(II) complexes having general formula [Pt(Lⁿ)Cl₂], (where, Lⁿ?=?L^1–4) were synthesized with neutral bidentate heterocyclic 1,3,5-trisubstituted bipyrazole based ligands. The synthesized compounds were characterized by physicochemical method such as TGA, molar conductance, micro-elemental analysis and magnetic moment, and spectroscopic method such as, FT-IR, UV–vis, ¹H NMR, ¹³C NMR and mass spectrometry. Biological applications of the compounds were carried out using in vitro brine shrimp lethality bioassay, in vitro antimicrobial study against five different pathogens, and cellular level cytotoxicity against Schizosaccharomyces pombe (S. Pombe) cells. Pt(II) complexes were tested for DNA interaction activities using electronic absorption titration, viscosity measurements study, fluorescence quenching technique and molecular docking assay. Binding constants (K_b) of ligands and complexes were observed in the range of 0.23–1.07?×?10⁵?M^?1 and 0.51–3.13?×?10⁵?M^?1, respectively. Pt(II) complexes (I–IV) display an excellent binding tendency to biomolecule (DNA) and possess comparatively high binding constant (K_b) values than the ligands. The DNA binding study indicate partial intercalative mode of binding in complex-DNA. The gel electrophoresis activity was carried out to examine DNA nuclease property of pUC19 plasmid DNA.     

Synthesis,DNA Binding,and Oxidative Cleavage Studies of Fe(II) and Co(III) Complexes Containing Bioactive Ligands

The two complexes containing bioactive ligands of the type and [Fe(L)] (PF₆)₂ (1) (where L = [1-{[2-{[2-hydroxynaphthalen-1-yl)methylidine]amino}phenyl)imino] methyl}naphthalene-2-ol]) and [Co(L₁L₂)] (PF₆)₃ (2) (where L₁L₂ = mixed ligand of 2-seleno-4-methylquinoline and 1,10-phenanthroline in the ratio 1:2, respectively) were synthesized and structurally characterized. The DNA binding property of the complexes with calf thymus DNA has been investigated using absorption spectra, viscosity measurements, and thermal denaturation experiments. Intrinsic binding constant K_b has been estimated at room temperature. The absorption spectral studies indicate that the complexes intercalate between the base pairs of the CT-DNA tightly with intrinsic DNA binding constant of 2.8 × 10⁵ M^?1 for (1) and 4.8 × 10⁵ M^?1 for (2) in 5 mM Tris-HCl/50 mM NaCl buffer at pH 7.2, respectively. The oxidative cleavage activity of (1) and (2) were studied by using gel electrophoresis and the results show that complexes have potent nuclease activity.     

Interactions of 5-(1-Pyrenyl)-10,15,20-tris(4-methylpyridinium)porphine with Double-Helix and Triple-Helix Nucleic Acids

Abstract

5-(1 -Pyrenyl)-10,15,20-tris(4-methylpyridinium)porphine (H₂PTMPP) having a porphyrin ring and a pyrenyl substituent was synthesized. The compound H₂PTMPP bound to poly(dA)?poly(dT) double helix and poly(dA)?2poly(dT) triple helix in different styles. The results of H₂PTMPP binding to oligonucleotides, dA₁₄?dT₁₄ and dA₁₄?2dT₁₄, was also shown.

     

SYNTHESIS AND BIOLOGICAL ACTIVITY OF 4-SUBSTITUTED 1-[1-(2-HYDROXYETHOXY)- METHYL-1,2,3-TRIAZOL-(4 & 5)-YLMETHYL]-1H-PYRAZOLO[3,4-d]PYRIMIDINES

The chemical synthesis of some 4-substituted 1-[1-(2-hydroxyethoxy)methyl-1,2,3-triazol-(4 and 5)-ylmethyl]-1H-pyrazolo[3,4-d]pyrimidines 12a,b, 13a,b and 14–23 as acyclic nucleosides is described. Treatment of (2-acetoxyethoxy)methylbromide with sodium azide afforded (2-acetoxyethoxy)methylazide 9. The heterocycles 6a,b were alkylated, separately, with propargyl bromide to obtain, regioselectively, 4-(methyl and benzyl)thio-1-(prop-2-ynyl)-1H-pyrazolo[3,4-d]pyrimidines 7a,b. These N₁-alkylated products were condensed with compound 9 via a 1,3-dipolar cycloaddition reaction to obtain, after separation and deprotection, 1,4 and 1,5-regioisomers 12a,b and 13a,b. The deprotected acyclic nucleosides 12a and 13a served as precursors for the preparation of 4-amino (14 and 15), 4-methylamino (16 and 17), 4-benzylamino (18 and 19), 4-methoxy (20 and 21) and 4-hydroxy (22 and 23) analogues. Compounds 7a,b and all deprotected acyclic nucleosides were evaluated for their inhibitory effects against the replication of HIV-1(III_B) and HIV-2(ROD) in MT-4 cells and for their anti-tumor activity. No marked activity was found. However, initial evaluation of 6a,b, 7a,b, 12a,b, 13a,b and 14–23 showed that compound 7b has marked activity against M. tuberculosis.     

An Improved Synthesis of 1-β-D-Arabinofuranosylcytosine 5′-Phosphate-L-1,2-diacylglycerols

Abstract

5′-O-MMTr-cytosine arabinoside was prepared on a large scale from 5′-O-MMTr-cytidine with diphenyl carbonate via 5′-protected cytidine-2′,3′-carbonate-aracytidine-2′,2-anhydro derivative at a 67 % yield. The synthesis of 1,2-L-dipalmitoyl-snglycerol, 1,2-L-distearoyl-sn-glycerol and 1,2-L-dioleoyl-sn-glycerol described here using 9-fluorenylmethoxycarbonyl (FMOC) group for protection of 3-position of glycerol which can be selectively removed by Et₃N treatment on the overall 60–70 % yield based on 1.2,-isopropilidene-sn-glycerol. These glycerols were phosphorylated first with 2-chlorophenyl-phosphoro-bis-triazolide quantitatively¹ in order to avoid acyl migration, then the glycerophosphate intermediates were condensed with 2′,3′,N⁴-trileulinyl-l-β-D-arabinofuranosylcytosine in the presence of 2-mesytilenesulphonyl chloride (MsCl) and 1 -methylimidazole (Melm)-which was used in the coupling of nucleotides²-^? in an 85–95 % yield compared with the low yielding diester method of Ryu³. Deblocking was carried out in two steps with tetrabutylammonium fluoride (TBAF) and hydrazine hydrate, producing target compouns (14a, 14b, 14c) at a 50 % yield.     

The structures of bis(1H,5H-S-methylisothiocarbonohydrazidium) di-μ-chloro-octachlorodibismuthate(III) tetrahydrate and tris(1H-S-methylisothiocarbonohydrazidium) esachlorobismuthate(III)

The structures of bis(1H⁺,5H⁺-S-methylisothiocarbonohydrazidium) di-μ-chlorooctachlorodibismuthate(III) tetrahydrate: (C₂H₁₀N₄S)₂(Bi₂Cl₁₀)· 4H₂O (compound [I]) and of tris(1H⁺-S-methylisothiocarbonohydrazidium) esachlorobismuthate(III): (C₂H₉N₄S)₃(BiCl_5.67I_0.33) (compound [II]) were determined from single crystal X-ray diffractometer data. Both compounds crystallize as triclinic (P ); crystals [I] with Z = 1 formula unit in a cell of constants: A = 10.621(3), B = 9.989(5), C = 7.439(3) Å, α = 88.31(2), β = 84.51(2), γ = 68.88(2)°, final R = 0.0427 for 2229 unique reflections with I 2σ(I); crystals [II] with Z = 2 and cell dimensions: A = 14.109(4), B = 12.209(9), C = 8.206(7) Å, α = 103.54(3), β = 104.95(2), γ = 81.96(2)°, final R = 0.0411 for 3637 unique reflections (1 2σ(I)). The structure of [I] is built up of diprotonated organic cations, water molecules and dinuclear centrosymmetric [Bi₂Cl₁₀]⁴⁻ anions held together by N-HCl, N-HO, O-HCl hydrogen bonds and Van der Waals interactions. The [Bi₂Cl₁₀]⁴⁻ complex consists of two edge-sharing octahedra in which three pairs of bonds of similar length are observed (Bi-Cl_av = 2.602(5), 2.712(4), 2.855(5) Å). The structure of [II] consists of monoprotonated cations and [BiCl_5.67I_0.33]³⁻ anions held together by a tridimensional network of hydrogen bonds. Each bismuth atom is octahedrally surrounded by six chlorine atoms, one of which is statistically substituted by a iodine atom.     

SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME 4-SUBSTITUTED 1-[1-(4-HYDROXYBUTYL)-1,2,3-TRIAZOL-(4 & 5)-YLMETHYL]-1H-PYRAZOLO-[3,4-d]PYRIMIDINES

The synthesis of 1-[1-(4-hydroxybutyl)-1,2,3-triazol-(4 and 5)-ylmethyl] -1H-pyrazolo[3,4-d]pyrimidines 11a,b, 12a,b and 13–17 as carboacyclic nucleosides is described. The compounds 8a,b were condensed, separately, with compound 7 via 1,3-dipolar cycloaddition reaction to afford, after separation and deprotection, 1,4-regioisomers 11a,b and 1,5-regioisomers 12a,b. The deprotected carboacyclic nucleosides 11a served as precursor for the preparation of 4-amino 13, 4-methylamino 14, 4-benzylamino 15, 4-methoxy 16 and 4-hydroxy 17 analogues. All deprotected carboacyclic nucleosides were evaluated for their inhibitory effects against the replication of HIV-1(III_B), HIV-2(ROD), various DNA viruses, a variety of tumor-cell lines and tuberculosis. No marked biological activity was found.