(3-苄基-4-芳酰基-1,2,4-三唑-5-基)(5-本基-1,3,4-噁二唑-2-基)硫醚的合成

通过3-苄基-4-芳酰基-1,2,4-三唑-5-巯基负离子在2-甲磺酰基-5-苯基-1,3,4-噁二唑环2-位上的亲核取代反应,制得13个新的(3-苄基-4-芳酰基-1,2,4-三唑-5-基)(5-苯基-1,3,4-噁二唑-2-基)硫醚衍生物.经元素分析、IR、~1H NMR和MS裂解碎片分析确认结构.初步观察了它们在0.01％浓度时对大肠杆菌繁殖的抑制作用.     

Synthesis and spectral studies of organotin(IV) 4-amino-3-alkyl-1,2,4-triazole-5-thionates: in vitro antimicrobial activity

Some di- and triorganotin(IV) triazolates of general formula, R(4-n)SnLn (where n=2; R=Me, n-Bu and Ph; n=1; R=Me, n-Pr, n-Bu and Ph and HL=4-amino-3-methyl-1,2,4-triazole-5-thiol (HL-1); and 4-amino-3-ethyl-1,2,4-triazole-5-thiol (HL-2)) were synthesized by the reaction of R(4-n)SnCln with sodium salt of HL-1 and HL-2. The bonding and coordination behavior in these derivatives have been discussed on the basis of IR and 119Sn M?ssbauer spectroscopic studies in the solid state. Their coordination behavior in solution is discussed by multinuclear (1H, 13C and 119Sn) NMR spectral studies. The IR and 119Sn M?ssbauer spectroscopic studies indicate that the ligands, HL-1 and HL-2 act as a monoanionic bidentate ligand, coordinating through Sexo- and Nring. The distorted skew trapezoidal-bipyramidal and distorted trigonal bipyramidal geometries have been proposed for R2SnL2 and R3SnL, respectively, in the solid state. In vitro antimicrobial screening of some of the newly synthesized derivatives and of some di- and triorganotin(IV) derivatives of 3-amino-1,2,4-triazole-5-thiol (HL-3) and 5-amino-3H-1,3,4-thiadiazole-2-thiol (HL-4) along with two standard drugs such as fluconazole and ciprofloxacin have been carried out against the bacteria, viz. Staphylococcus aureus and Escherichia coli, and against some fungi, viz. Aspergillus fumigatus, Candida albicans, Candida albicans (ATCC 10231), Candida krusei (GO3) and Candida glabrata (HO5) by the filter paper disc method. The studied organotin(IV) compounds show mild antifungal activity as compared to that of fluconazole, however, they show almost insignificant activity against the studied Gram-positive (Staphylococcus aureas) and Gram-negative (Escherichia coli) bacteria as compared to that of standard drug, ciprofloxacin.     

3-间硝基苯基/对硝基苯基-6-芳基-1, 2, 4-三唑并[3, 4-b]-1, 3, 4-噻二唑衍 生物的合成

报道了以3-间硝基苯基/对硝基苯基-4-氨基-5-巯基-1,2,4-三唑与芳酸在磷酰氯的作用下,合成了16个标题化合物,并研究了合成反应的条件。观察了部分标题化合物对金黄色葡萄球菌和大肠杆菌有明显的抑菌作用。     

Preparation of some 2,3,5,6,7,8,8a-heptahydrothiazolo[3,2-a]-s-triazine-5,7-diones

A number of 2-substituted-2-thiazolines have been found to react readily with two moles of isocyanic acid in ethereal solution to give 2, 3, 5, 6, 7, 8, 8a-heptahydrothiazolo-[3,2-a]-s-triazine-5, 7-diones (IIa-e). Preliminary reports indicate some activity of these compounds against Walker's carcinosarcoma 256 in rats.     

Binuclear copper(II) complexes of 5-nitrosalicylaldehyde N(3)-substituted thiosemicarbazones

Summary Binuclear copper(II) complexes with six 5-nitrosalicylaldehyde N(3)-substituted thiosemicarbazones have been prepared and characterized. I.r., electronic and e.s.r. spectra of the complexes, as well as i.r., electronic, and ¹H-and ¹³C-n.m.r. spectra of the thiosemicarbazones, have been obtained. The crystal structure of a monomeric copper(II) complex of 5-nitrosalicylaldehyde piperidyl-thiosemicarbazone, H₂5NO₂Sapip, grown from DMF solution, has been solved. Neither the thiosemicarbazones or their binuclear copper(II) complexes show growth inhibitory activity against Aspergillus niger, but the copper(II) complexes show some activity against the fungus Paecilomyces variotii.     

Photochemische und chemische Synthesen biologisch aktiver 3-Oxazoline

Photochemical and Chemical Syntheses of Biologically Active 3-Oxazolines Using the photoreaction of 2H-azirines with carbonyl compounds, the 2,2-dimethyl-3-oxazolines 5a, 5b , and 6a have been obtained which bear a mono- or dichlorophenyl substituent at C(4) of the five-membered heterocycle and pyridyl at C(5). These compounds exhibit interesting activities against phytopathogenic fungi. Because 6a had been selected for field testing, its photochemical preparation was supplemented by a chemical synthesis. However, the overall performance of 6a in the field was inferior to some of the recently introduced agricultural fungicides of the ergosterol biosynthesis inhibitor type. Although 16 additional 3-oxazolines with varied substituents have been prepared, the fungicidal activity found with 6a could not be improved.     

Synthesis of 5-alkoxymethyl derivatives of 3'-amino-2',3'-dideoxyuridine and evaluation of their activity against HIV and cancer.

5-Alkoxymethyluracils 2a-c have been prepared by acid-catalyzed etherification of 5-hydroxymethyluracil (1). Compounds 1, 2a-c, 5-methoxymethyl- and 5-benzyloxymethyl-uracil were silylated and coupled with 1,5-di-O-acetyl-3-phthalimido-2,3-dideoxy-beta- D-erythro-pentofuranose (3), in the presence of trimethylsilyl triflate as a catalyst, to give the corresponding 3'-phthalimido-2',3'-dideoxynucleosides 5a-f and 6 which on treatment with 33% methylamine-ethanol afforded the corresponding 3'-amino-2',3'-dideoxynucleosides 7a-f and 8 in high yields. Compound 7d showed colony inhibition when tested against human epidermoid cervical cancer cells. Nucleosides 5a-e, 7a-f and 8 did not show any significant activity against HIV-1.     

New synthesis of 2',3'-didehydro-2',3'-dideoxynucleosides.

The 3'-iodonucleoside 4 and the 3'-O-methylsulfonylthymidine 9 have been synthesized by condensation of silylated uracils 2 with methyl 5-O-tert-butyldiphensilyl-2,3-dideoxy-3-iodo-D-threo-pentofuran oside (3) and methyl 5-O-tert-butyldiphenylsilyl-2-deoxy-3-methylsulfonyl-D-erythro- pentofuranoside (8), respectively. The nucleoside 4 and 9 produced the corresponding 2',3'-didehydro-2',3'-dideoxynucleosides 5 in an elimination reaction on treatment with sodium methoxide. The compounds 5b showed no antiviral activity against HIV-1.     

3-(N-取代苯基-2-乙酰胺基)硫基-4-N-取代邻羟苯基亚胺基-5-甲基-1,2,4-三唑类化合物的合成及生物活性研究

以对称二氨基硫脲为原料,与冰醋酸反应生成5-甲基-4-氨基-1,2,4-三唑-3-硫酮(1);在弱酸性条件下,1与取代水杨醛反应生成席夫碱中间体5-甲基-4-(N-取代邻羟苯基)亚胺基-1,2,4-三唑-3-硫酮(2a～2c);最后在碱性条件下分别与N-取代苯基-2-氯乙酰胺发生烷基化反应生成15种未见报道的目标化合物3-(N-取代苯基-2-乙酰胺基)硫基-4-(N-取代邻羟苯基)亚胺基-5-甲基-1,2,4-三唑(3a～3o),其结构经IR,1H NMR,13C NMR确证.初步生物测试表明,质量分数为0.01%时,3a～3o对白色念珠菌的抑菌率均达90%以上,具有很强的抑菌活性;对金黄色葡萄球菌、大肠杆菌的抑菌率达80%以上,具有较强的抑菌活性.     

Wisanin und andere amide der 5-(2-methoxy-4,5-methylendioxyphenyl)-2,4-pentadiensäure: Synthesen,spektroskopische untersuchungen und prüfung auf antibakterielle wirksamkeit

Wisanine, a constituent of piper guineense (a plant of which antibacterial activity has been reported and other amides of 5 - (2 - methoxy - 4, 5 - methylenedioxyphenyl) - pentadienoic acid were synthesized from 3,4 -dioxymethylen - phenel and investigated spectroscopically. The amides prepared have been tested against grampositive and gramnegative bacteria. Only some of the amides prepared show weak antibacterial activity.     

Synthesis of some 3',5'-dideoxy-5'-C-phosphonomethyl nucleosides.

Ammonium [1-(3',5',6'-trideoxy-beta-D-erythro-hexofuranosyl)thymine]-6'- phosphonate (1), ammonium 3',5'-dideoxycytidine-5'-C-methylphosphonate (2) and 3',5'-dideoxyadenosine-5'-C-methyl phosphonic acid (3) have been synthesized and tested for anti-HIV activity. The key steps involved an Arbuzov reaction between triethyl phosphite and 3,5,6-trideoxy-6-iodo-1,2-O-isopropylidene-alpha-D-erythro- hexofuranose (7), followed by condensation with the appropriate nucleoside bases. The substances 1, 2 and 3 have been tested in vitro against HIV.     

Synthesis of Novel 3-Substituted Pyridothienopyrimidine Derivatives with Biological Evaluation as Antimicrobial Agents

Novel 3-substituted pyridothienopyrimidine derivatives have been synthesized via the reaction of 2-{7,9-dimethyl-4-oxopyrido[3',2':4,5]thieno[3,2-d]pyrimidin-3(4H)-yl}acetohydrazide(5) with a variety of active reagents and chemicals. Structures of the newly synthesized compounds were established based on spectral data. The resulting pyridothienopyrimidine derivatives were evaluated for their possible antimicrobial activity and some of them represent a new class of potentially antimicrobial compounds, especially compounds 9 and 18 which displayed the highest activity against Gram-positive bacteria, Gram-negative bacteria, and Fungi in MIC range of 0.12-1.95 μg/mL.     

3-(5′-乙氧基-1,3,4-噻二唑-2′-亚甲氨基)-2-氰基-3-取代-丙烯酸酯类化合物的合成、晶体结构及生物活性

采用氰基丙烯酸酯与5-乙氧基-1,3,4-噻二唑-2-甲氨在乙醇中加热回流的方法合成了一系列3-(5′-乙氧基-1,3,4-噻二唑-2′-亚甲氨基)-2-氰基-3-取代-丙烯酸酯类化合物.目标化合物结构均经1HNMR和元素分析确证.生物活性测试结果表明,部分化合物对双子叶杂草油菜和苋菜显示出较好的除草活性及良好的选择性,用化合物6j在600g/ha剂量下对油菜和苋菜茎叶进行处理,抑制率仍达100%和95.2%,与对照样B相当;氰基丙烯酸酯3位取代基体积对除草活性影响较大,3位为异丙基时活性最高.     

Synthesis and Anti‐inflammatory Screening of Some Mono and Bis‐Alkoxyphthalimide Linked Benzimidazole and their Quinazoline and Pyrimidine Derivatives

In the present study, synthesis of some nonsymmetrical 2‐(1H‐benzimidazol‐2‐ylamino)‐7,7‐dimethyl‐7,8‐dihydroquinazolin‐5(6H)‐one ( 3 ) and substituted‐(1H‐benzo[d]imidazol‐2‐yl)amino‐pyrimidine derivatives ( 4a , 4b , 4c and 5a , 5b ) is described as a three‐component reaction of 2‐guanidinobenzimidazole ( 2 ) with triethyl orthoformate and different reactive methylene compounds. Subsequent condensation of compounds 3 , 4a , 4b , 4c , and 5a , 5b with bromoethoxyphthalimide ( 1 ) gave final compounds 6 , 7a , 7b , 7c , and 8a , 8b . Synthesized final compounds have been screened for their in‐vivo anti‐inflammatory activity against carrageenan‐induced paw edema in albino rats. Diclofenac was used as standard anti‐inflammatory agents. Some of the compounds exhibited significant anti‐inflammatory activity, as compared to standard drug. Structures of synthesized compounds have been confirmed on the basis of chemical tests and spectral studies.     

Synthesis, antimicrobial and antiproliferative activity of novel silver(I) tris(pyrazolyl)methanesulfonate and 1,3,5-triaza-7-phosphadamantane complexes

Five new silver(I) complexes of formulas [Ag(Tpms)] (1), [Ag(Tpms)(PPh(3))] (2), [Ag(Tpms)(PCy(3))] (3), [Ag(PTA)][BF(4)] (4), and [Ag(Tpms)(PTA)] (5) {Tpms = tris(pyrazol-1-yl)methanesulfonate, PPh(3) = triphenylphosphane, PCy(3) = tricyclohexylphosphane, PTA = 1,3,5-triaza-7-phosphaadamantane} have been synthesized and fully characterized by elemental analyses, (1)H, (13)C, and (31)P NMR, electrospray ionization mass spectrometry (ESI-MS), and IR spectroscopic techniques. The single crystal X-ray diffraction study of 3 shows the Tpms ligand acting in the N(3)-facially coordinating mode, while in 2 and 5 a N(2)O-coordination is found, with the SO(3) group bonded to silver and a pendant free pyrazolyl ring. Features of the tilting in the coordinated pyrazolyl rings in these cases suggest that this inequivalence is related with the cone angles of the phosphanes. A detailed study of antimycobacterial and antiproliferative properties of all compounds has been carried out. They were screened for their in vitro antimicrobial activities against the standard strains Enterococcus faecalis (ATCC 29922), Staphylococcus aureus (ATCC 25923), Streptococcus pneumoniae (ATCC 49619), Streptococcus pyogenes (SF37), Streptococcus sanguinis (SK36), Streptococcus mutans (UA159), Escherichia coli (ATCC 25922), and the fungus Candida albicans (ATCC 24443). Complexes 1-5 have been found to display effective antimicrobial activity against the series of bacteria and fungi, and some of them are potential candidates for antiseptic or disinfectant drugs. Interaction of Ag complexes with deoxyribonucleic acid (DNA) has been studied by fluorescence spectroscopic techniques, using ethidium bromide (EB) as a fluorescence probe of DNA. The decrease in the fluorescence of DNA-EB system on addition of Ag complexes shows that the fluorescence quenching of DNA-EB complex occurs and compound 3 is particularly active. Complexes 1-5 exhibit pronounced antiproliferative activity against human malignant melanoma (A375) with an activity often higher than that of AgNO(3), which has been used as a control, following the same order of activity inhibition on DNA, i.e., 3 > 2 > 1 > 5 > AgNO(3)? 4.     

Synthesis and Biological Study of Some 4-oxo-Thiazolidine Derivatives of 2-Aminothiazole

Conventional and microwave assisted synthesis of new series of N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐5‐(substituted benzylidene)‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 5a–5m have been developed. The cycloaddition reaction of thioglycolic acid with N‐{2‐(substituted benzylidenehydrazino)‐ethyl}‐2‐aminothiazole 3a–3m in the presence of anhydrous ZnCl₂ afforded new heterocyclic compounds N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 4a–4m . The later product on treatment with several selected substituted aromatic aldehydes in the presence of C₂H₅ONa undergoes Knoevenagel reaction to yield 5a–5m . The structures of compounds 1 , 2 , 3a–3m , 4a–4m and 5a–5m were confirmed by IR, ¹H NMR, ¹³C NMR, FAB‐Mass and chemical analysis. All above compounds were screened for their antimicrobial activities against some selected bacteria and fungi and antituberculosis study against M. tuberculosis.     

Enzyme inhibitory constituents from Duranta repens

Isoprenylated flavonoids 5,7-dihydroxy-3'-(2-hydroxy-3-methyl-3-butenyl)-3,6,4'-trimethoxyflavone (1), 3,7-dihydroxy-3'-(2-hydroxy-3-methyl-3-butenyl)-5,6,4'-trimethoxyflavone (2) and an isoprenylated acetophenone derivative (3) have been isolated from Duranta repens along with known compounds, 5-hydroxy-3,6,7,4'-tetramethoxyflavone (4), rosenonolactone (5), 6,7-dimethoxycoumarin (6), 5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (7) and 5alpha,8alpha-epidioxyergosta-6,9(11),22-trien-3beta-ol (8), isolated for the first time from this species. Their structures and the relative configuration were determined by spectroscopic methods (1H- and 13C-NMR, IR, UV and MS) and two-dimensional (2D)-NMR experiments. The compounds 1-5 showed inhibitory activity against prolyl endopeptidase while 4 and 5 were also active against thrombin.     

Synthesis,Spectroscopic Studies of Fluorinated Pyrimido‐1,2,4‐Triazines: Protective Effect Against Some Plant Pathogenic Fungi

In search for new biologically active compounds, several new fluorine‐substituted pyrimido [2,3‐c][1,2,4]triazino ( 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ) have been synthesized via the nucleophilic attack of 2‐hydrazinopyrimidinone ( 2 ) toward more positive carbons under different conditions. Structure of the newly synthesized compounds was deduced from elemental analyses as well as their spectral data (UV, IR, NMR, and M/S). The antifungal activity of the target ring systems has been evaluated both in vitro and in vivo against some phytopathogenic fungi associated with wheat grains. Result showed that compounds 6 , 7 , and 8 have high protection of wheat grains against the fungal infection.     

Antimicrobial activity studies of the binuclear metal complexes derived from tridentate Schiff base ligands

Three novel tridentate Schiff base ligands derived fromthe 3-hydroxysalicylaldehyde (H₂L¹), 4-hydroxysalicylaldehyde (H₂L²) and 5-bromosalicylaldehyde (H₂L³) with a new amine N-(pyridyl)-2-hydroxy-3-methoxy-5-aminobenzylamine (2) have been prepared. The ligands and their metal complexes have been characterized by elemental analyses, conductivity and magnetic susceptibility measurements, i.r., electronic absorption and ¹H and ¹³C n.m.r. spectroscopy. All complexes are binuclear and, in some, the H₂O molecules are coordinated to the metal ion. Antimicrobial activities of the ligands and their complexes have been tested against to the Bacillus subtilis IMG 22 (bacteria), Micrococcus luteus LA 2971 (bacteria) Saccharamyces cerevisiae WET 136 (yeast), and Candida albicans CCM 314 (yeast). Thermal properties of all complexes have been studied by t.g. and d.t.a techniques.     

New triorganotin (IV) derivatives of dipeptides as models for metal-protein interactions: synthesis, structural characterization and biological studies

New non-electrolytic triorganotin(IV) derivatives of dipeptides with general formulae R3Sn(HL), where R = Ph and HL = monoanion of glycylisoleucine (H2L-1), valylvaline (H2L-2), alanylvaline (H2L-3), leucylalanine (H2L-4), leucylleucine (H2L-5); R = n-Bu and HL = monoanion of glycylisoleucine (H2L-1) and leucylalanine (H2L-4); and R = Me and HL = monoanion of leucylalanine (H2L-4) have been synthesized and characterized on the basis of infrared, multinuclear 1H, 13C and 119Sn NMR and 119Sn M?ssbauer spectroscopic studies. These investigations suggest that all the ligands in R3Sn(HL) act as monoanionic bidentates coordinating through the COO- and NH2 groups. The 119Sn M?ssbauer studies, together with the NMR data, indicate that, for these polymeric derivatives, the polyhedron around tin in R3Sn(HL) is a trigonal-bipyramid with the three organic groups in the equatorial positions, while the axial positions are occupied by a carboxylic oxygen and the amino nitrogen atom from the adjacent molecule. The anti-inflammatory and cardiovascular activities and toxicity of all these compounds have been determined. Four of the complexes have also been screened against some of the chosen bacterial and fungal strains. The Ph3Sn(IV) compounds exhibit better anti-inflammatory and cardiovascular activities in comparison to the Me3Sn(IV) and n-Bu3Sn(IV) analogues. n-Bu3Sn(Gly-Ile) and Ph3Sn(Ala-Val) exhibit good antibacterial activity against all the chosen strains.