Syntheses and biological activities of novel diheterocyclic compounds containing 1,2,4‐triazolo[1,5‐a]pyrimidine and 1,3,4‐oxadiazole

In a search for novel agrochemicals with high activity and low toxicity, a series of diheterocyclic compounds containing 1,2,4‐triazolo[1,5‐a]pyrimidine and 1,3,4‐oxadiazole rings were designed and synthesized by a four‐step synthetic route starting from 2‐mercapto‐5,7‐dimethyl‐1,2,4‐triazolo[1,5‐a]pyrimidine. The structures of all the compounds synthesized were confirmed by ¹H NMR, mass spectroscopy and elemental analysis. The preliminary bioassay against Brassica campestris L and Echinochloa crusgalli Beavu indicated that the title compounds displayed herbicidal activity at the concentration of 100 ppm and that compounds 5a (R = CH₃), 5d (R = C₂H₅) and 5f (R = i‐Bu) were found to have particularly high activities. In addition, the results of an in vivo test at a concentration of 50 ppm showed that all the compounds prepared were highly active against Rhizoctonia slain, but not active against Fusarium oxysporum, Gibberella zeave and Phoma sparagi. A further in vivo test showed that compound 5j possessed better fungicidal activity against Rhizoctonia solani at a concentration of 200 ppm than Carbendazim and Validamycin A, which are well known for their fungicidal activity against Rhizoctonia solani. To our knowledge, this is the first report that 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives display fungicidal activity against Rhizoctonia solani. © 2001 Society of Chemical Industry     

Synthesis and biological activity of medium molecular weight polymers containing 3,6‐endo‐methylene‐1,2,3,6‐tetrahydrophthalimidobutanoyl‐5‐fluorouracil

A new monomer, 3,6‐endo‐methylene‐1,2,3,6‐tetrahydrophthalimidobutanoyl‐5‐fluorouracil (ETBFU), was synthesized by reaction of 3,6‐endo‐methylene‐1,2,3,6‐tetrahydrophthalimidobutanoyl chloride and 5‐fluorouracil. The homopolymer of ETBFU and its copolymers with acrylic acid (AA) or vinyl acetate (VAc) were prepared by photopolymerization using 2,2‐dimethoxy‐2‐phenylacetophenone as an initiator at 25 °C. The synthesized ETBFU and its polymers were identified by FTIR, ¹H NMR and ¹³C NMR spectroscopies. The ETBFU content in poly(ETBFU‐co‐AA) and poly(ETBFU‐co‐VAc) was 43 and 14 mol%, respectively. The apparent number‐average molecular weight (M_n) of the polymers determined by GPC ranged from 8400 to 11 300. The in vitro cytotoxicity of the samples against mouse mammary carcinoma (FM3A), mouse leukaemia (P388), and human histiocytic lymphoma (U937) cancer cell lines decreased in the order 5‐FU ≥ ETBFU > poly(ETBFU) > poly(ETBFU‐co‐AA) > poly(ETBFU‐co‐VAc). The in vivo antitumour activity of the polymers against Balb/C mice bearing sarcoma 180 tumour cells was greater than that of 5‐fluorouracil at all doses tested. © 2000 Society of Chemical Industry     

Chemoenzymatic Synthesis of GDP‐L‐Fucose Derivatives as Potent and Selective α‐1,3‐Fucosyltransferase Inhibitors

Fucosyltransferases (FucTs) usually catalyze the final step of glycosylation and are critical to many biological processes. High levels of specific FucT activities are often associated with various cancers. Here we report the development of a chemoenzymatic method for synthesizing a library of guanosine diphosphate β‐L ‐fucose (GDP‐Fuc) derivatives, followed by in situ screening for inhibitory activity against bacterial and human α‐1,3‐FucTs. Several compounds incorporating appropriate hydrophobic moieties were identified from the initial screening. These were individually synthesized, purified and characterized in detail for their inhibition kinetics. Compound 5 had a K_i of 29 nM for human FucT‐VI, and is 269 and 11 times more selective than for Helicobacter pylori FucT (K_i=7.8 μM) and for human FucT‐V (K_i=0.31 μM).     

Synthesis and biological activity of medium range molecular weight polymers containing exo‐3,6‐epoxy‐1,2,3,6‐tetrahydrophthalimidocaproic acid

A new monomer, exo‐3,6‐epoxy‐1,2,3,6‐tetrahydrophthalimidocaproic acid (ETCA), was prepared by reaction of maleimidocaproic acid and furan. The homopolymer of ETCA and its copolymers with acrylic acid (AA) or with vinyl acetate (VAc) were obtained by photopolymerizations using 2,2‐dimethoxy‐2‐phenylacetophenone as an initiator at 25 °C. The synthesized ETCA and its polymers were identified by FTIR, ¹H NMR and ¹³C NMR spectroscopies. The apparent average molecular weights and polydispersity indices determined by gel permeation chromatography (GPC) were as follows: M_n = 9600 g mol^?1, M_w = 9800 g mol^?1, M_w/M_n = 1.1 for poly(ETCA); M_n = 14 300 g mol^?1, M_w = 16 200 g mol^?1, M_w/M_n = 1.2 for poly(ETCA‐co‐AA); M_n = 17 900 g mol^?1, M_w = 18 300 g mol^?1, M_w/M_n = 1.1 for poly(ETCA‐co‐VAc). The in vitro cytotoxicity of the synthesized compounds against mouse mammary carcinoma and human histiocytic lymphoma cancer cell lines decreased in the following order: 5‐fluorouracil (5‐FU) ≥ ETCA > polymers. The in vivo antitumour activity of the polymers against Balb/C mice bearing sarcoma 180 tumour cells was greater than that of 5‐FU at all doses tested. © 2001 Society of Chemical Industry     

Beziehungen zwischen algistatischer Aktivität und physikalisch‐chemischen Eigenschaften von 5‐Amino‐1‐aryl‐1H‐tetrazolen

A series of 20 5‐amino‐1‐aryl‐1H‐tetrazoles was synthesized by diazotation of corresponding 1‐amino‐3‐aryl‐guanidines and tested for growth‐inhibiting activity against autotrophic Chlorella vulgaris cultures. In the used tests the different algae growth was quantified by photometric measurements at 680 nm. From obtained dosage‐effectivity relationships the reciprocal values of isoeffective concentrations c ₅₀ were derived and defined as activity parameters A in QSAR (quantitative structure‐activity relationship) studies. It could be shown that the algistatitic activity (log A) of the tested heterocycles strongly depends on hydrophobicity described by their octan‐1‐ol/water partition coefficients (log P). The calculated linear relationships between log A and log P can be significantly improved by separate treatment of meta‐/para‐ and ortho‐substituted compounds or using an indicator variable to describe the lower activity of ortho‐substituted 5‐ami‐no‐1‐aryl‐1H‐tetrazoles in common regression equations. The results are discussed and compared with analogous QSAR found for earlier tested series of N‐heterocycles and compounds with urea structure.     

(R)‐α‐Lipoyl‐Glycyl‐L‐Prolyl‐L‐Glutamyl Dimethyl Ester Codrug as a Multifunctional Agent with Potential Neuroprotective Activities

The (R)‐α‐lipoyl‐glycyl‐L ‐prolyl‐L ‐glutamyl dimethyl ester codrug (LA‐GPE, 1 ) was synthesized as a new multifunctional drug candidate with antioxidant and neuroprotective properties for the treatment of neurodegenerative diseases. Physicochemical properties, chemical and enzymatic stabilities were evaluated, along with the capacity of LA‐GPE to penetrate the blood–brain barrier (BBB) according to an in vitro parallel artificial membrane permeability assay for the BBB. We also investigated the potential effectiveness of LA‐GPE against the cytotoxicity induced by 6‐hydroxydopamine (6‐OHDA) and H₂O₂ on the human neuroblastoma cell line SH‐SY5Y by using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) reduction assay. Our results show that codrug 1 is stable at both pH 1.3 and 7.4, exhibits good lipophilicity (log P=1.51) and a pH‐dependent permeability profile. Furthermore, LA‐GPE was demonstrated to be significantly neuroprotective and to act as an antioxidant against H₂O₂‐ and 6‐OHDA‐induced neurotoxicity in SH‐SY5Y cells.     

Synthesis and antitumour and antiangiogenesis activity of polymers containing methacryloyl‐2‐oxy‐1,2,3‐propane tricarboxylic acid

A new monomer, methacryloyl‐2‐oxy‐1,2,3‐propane tricarboxylic acid (MTCA), was synthesized from citric acid and methacrylic anhydride. Poly(methacryloyl‐2‐oxy‐1,2,3‐propane tricarboxylic acid) and poly(methacryloyl‐2‐oxy‐1,2,3‐propane tricarboxylic acid)‐co‐(maleic anhydride) were prepared by radical polymerizations. Terpoly(methacryloyl‐2‐oxy‐1,2,3‐propane tricarboxylic acid–maleic anhydride–furan) was obtained by in situ terpolymerization of MTCA and exo‐3,6‐epoxy‐1,2,3,6‐tetrahydrophthalic anhydride. The synthesized samples were identified by FTIR, ¹H NMR and ¹³C NMR spectroscopies. The number‐average molecular weights of the fractionated polymers determined by GPC were in the range 14 900–16 600 and polydispersity indices were less than 1.14. The in vitro IC₅₀ values of the monomer and polymers against cancer and normal cell lines were much higher than those of 5‐fluorouracil (5‐FU). The in vivo antitumour activities of the synthesized samples at a dosage of 0.8 mg kg⁻¹ against mice bearing the sarcoma 180 tumour cell line decreased in the order terpoly(MTCA‐MAH‐FUR) > poly(MTCA‐co‐MAH) > poly(MTCA) > MTCA > 5‐FU. The synthesized samples inhibited DNA replication and angiogenetic activity more than did 5‐FU. © 2001 Society of Chemical Industry     

Organosoluble and light‐colored fluorinated polyimides based on 1,1‐bis[4‐(4‐amino‐2‐trifluoromethylphenoxy)phenyl]‐1‐phenylethane and various aromatic dianhydrides

To investigate the CF₃ group affecting the coloration and solubility of polyimides (PI), a novel fluorinated diamine 1,1‐bis[4‐(4‐amino‐2‐ trifluoromethylphenoxy)phenyl]‐1‐phenylethane (2) was prepared from 1,1‐ bis(4‐hydrophenyl)‐1‐phenylethan and 2‐chloro‐5‐nitrobenzotrifluoride. A series of light‐colored and soluble PI 5 were synthesized from 2 and various aromatic dianhydrides 3a–f using a standard two‐stage process with thermal 5a– f(H) and chemical 5a–f(C) imidization of poly(amic acid). The 5 series had inherent viscosities ranging from 0.55 to 0.98 dL/g. Most of 5a–f(H) were soluble in amide‐type solvents, such as N‐methyl‐2‐pyrrolidone (NMP), N,N‐ dimethylacetamide (DMAc), and N,N‐dimethylformamide (DMF), and even soluble in less polar solvents, such as m‐Cresol, Py, Dioxane, THF, and CH₂Cl₂, and the 5(C) series was soluble in all solvents. The GPC data of the 5a–f(C) indicated that the Mn and Mw values were in the range of 5.5–8.7 × 10⁴ and 8.5–10.6 × 10⁴, respectively, and the polydispersity index (PDI) Mw /Mn values were 1.2–1.5. The PI 5 series had excellent mechanical properties. The glass transition temperatures of the 5 series were in the range of 232–276°C, and the 10% weight loss temperatures were at 505–548 °C in nitrogen and 508–532 °C in air, respectively. They left more than 56% char yield at 800°C in nitrogen. These films had cutoff wavelengths between 356.5–411.5 nm, the b* values ranged from 5.0–71.1, the dielectric constants, were 3.11–3.43 (1MHz) and the moisture absorptions were in the range of 011–0.40%. Comparing 5 containing the analogous PI 6 series based on 1,1‐bis[4‐(4‐aminophenoxy)phenyl]‐1‐ phenylethane (BAPPE), the 5 series with the CF₃ group showed lower color intensity, dielectric constants, and better solubility. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 2399–2412, 2005     

Ethylene/1‐octadecene copolymerization using [η5:η1‐C5Me4‐4‐R1‐6‐R‐C6H2O]TiCl2 catalysts

Copolymerization of ethylene with 1‐octadecene was studied using [η⁵:η¹‐C₅Me₄‐4‐R₁‐6‐R‐C₆H₂O]TiCl₂ [R₁ = ^tBu (1), H (2, 3, 4); R = ^tBu (1, 2), Me (3), Ph (4)] as catalysts in the presence of Al(i‐Bu)₃ and [Ph₃C][B(C₆F₅)₄]. The effect of the concentration of comonomer in the feed and Al/Ti molar ratio on the catalytic activity and molecular weight of the resultant copolymer were investigated. The substituents on the phenyl ring of the ligand affect considerably both the catalytic activity and comonomer incorporation. The 1 /Al(i‐Bu)₃/[Ph₃C][B(C₆F₅)₄] catalyst system exhibits the highest catalytic activity and produces copolymers with the highest molecular weight, while the 2 /Al(i‐Bu)₃/[Ph₃C][B(C₆F₅)₄] catalyst system gives copolymers with the highest comonomer incorporation under similar conditions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Synthesis and biological activity of phthalimide‐based polymers containing 5‐fluorouracil

The attachment of anticancer agents to polymers is a promising approach towards reducing the toxic side‐effects and retaining the potent antitumour activity of these agents. A new tetrahydrophthalimido monomer containing 5‐fluorouracil (ETPFU) and its homopolymer and copolymers with acrylic acid (AA) and with vinyl acetate (VAc) have been synthesized and spectroscopically characterized. The ETPFU contents in poly(ETPFU‐co‐AA) and poly(ETPFU‐co‐VAc) obtained by elemental analysis were 21 mol% and 20 mol%, respectively. The average molecular weights of the polymers determined by gel permeation chromatography were as follows: M_n = 8900 g mol^?1, M_w = 13 300 g mol^?1, M_w/M_n = 1.5 for poly(ETPFU); M_n = 13 500 g mol^?1, M_w = 16 600 g mol^?1, M_w/M_n = 1.2 for poly(ETPFU‐co‐AA); M_n = 8300 g mol^?1, M_w = 11 600 g mol^?1, M_w/M_n = 1.4 poly(ETPFU‐co‐VAc). The in vitro cytotoxicity of the compounds against FM3A and U937 cancer cell lines increased in the following order: ETPFU > 5‐FU > poly(ETPFU) > poly(ETPFU‐co‐AA) > poly(ETPFU‐co‐VAc). The in vivo antitumour activities of all the polymers in Balb/C mice bearing the sarcoma 180 tumour cell line were greater than those of 5‐FU and monomer at the highest dose (800 mg kg^?1). © 2002 Society of Chemical Industry     

Characteristics of poly(AAc5‐co‐HPMA3‐cl‐EGDMA15) hydrogel‐immobilized lipase of Pseudomonas aeruginosa MTCC‐4713

Four series of noble networks were synthesized with acrylic acid (AAc) copolymerized with varying amount of 2‐hydroxy propyl methacrylate or dodecyl methacrylate (AAc/HPMA or AAc/DMA; 5:1 to 5:5, w/w) in the presence of ethylene glycol dimethacrylate (EGDMA; 1, 5, 10, 15, and 20%, w/w) as a crosslinker and ammonium per sulfate (APS) as an initiator. Each of the networks was used to immobilize a purified lipase from Pseudomonas aeruginosa MTCC‐4713. The lipase was purified by successive salting out with (NH₄)₂SO₄, dialysis, and DEAE anion exchange chromatography. Two of the matrices, E_15a, i.e. [poly (AAc₅‐co‐DMA₁‐cl‐EGDMA₁₅)] and I_15c, i.e. [poly (AAc₅‐co‐HPMA₃‐cl‐EGDMA₁₅)], that showed relatively higher binding efficiency for lipase were selected for further studies. I_15c‐hydrogel retained 58.3% of its initial activity after 10th cycle of repetitive hydrolysis of p‐NPP, and I_15c was thus catalytically more stable and efficient than the other matrix. The I_15c‐hydrogel‐immobilized enzyme showed maximum activity at 65°C and pH 9.5. The hydrolytic activity of free and I_15c‐hydrogel‐immobilized enzyme increased profoundly in the presence of 5 mM chloride salts of Hg²⁺, NH₄⁺, Al³⁺, K⁺, and Fe³⁺. The immobilized lipase was preferentially active on medium chain length p‐nitrophenyl acyl ester (C:8, p‐nitrophenyl caprylate). © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4636–4644, 2006     

Monoamine Oxidase (MAO) Inhibitory Activity: 3‐Phenylcoumarins versus 4‐Hydroxy‐3‐phenylcoumarins

Monoamine oxidase (MAO) is a useful target in the treatment of neurodegenerative diseases and depressive disorders. Both isoforms, MAO‐A and MAO‐B, are known to play critical roles in disease progression, and as such, the identification of novel, potent and selective inhibitors is an important research goal. Here, two series of 3‐phenylcoumarin derivatives were synthesized and evaluated against MAO‐A and MAO‐B. Most of the compounds tested acted preferentially on MAO‐B, with IC₅₀ values in the micromolar to nanomolar range. Only 6‐chloro‐4‐hydroxy‐3‐(2’‐hydroxyphenyl)coumarin exhibited activity against the MAO‐A isoform, while still retaining good selectivity for MAO‐B. 6‐Chloro‐3‐phenylcoumarins unsubstituted at the 4 position were found to be more active as MAO‐B inhibitors than the corresponding 4‐hydroxylated coumarins. For 4‐unsubstituted coumarins, meta and para positions on the 3‐phenyl ring seem to be the most favorable for substitution. Molecular docking simulations were used to explain the observed hMAO‐B structure–activity relationships for this type of compound. 6‐Chloro‐3‐(3’‐methoxyphenyl)coumarin was the most active compound identified (IC₅₀=0.001 μM ) and is several times more potent and selective than the reference compound, R‐(?)‐deprenyl hydrochloride. This compound represents a novel tool for the further investigation of the therapeutic potential of MAO‐B inhibitors.     

(2,2‐Diphenyl‐[1,3]oxathiolan‐5‐ylmethyl)‐(3‐phenyl‐propyl)‐amine: a Potent and Selective 5‐HT1A Receptor Agonist

A selective 5‐HT _1A receptor agonist : A new series of ligands acting at 5‐HT_1A serotonin receptor were identified. Among them (2,2‐diphenyl‐[1,3]oxathiolan‐5‐yl‐methyl)‐(3‐phenyl‐propyl)amine (shown) possesses outstanding activity (pK_i=8.72, pD₂=7.67, E_max=85) and selectivity (5‐HT_1A/α_1D>150), and represents a new 5‐HT_1A agonist chemotype.

     

siRNA Modified with 2′‐Deoxy‐2′‐C‐methylpyrimidine Nucleosides

(2′S)‐2′‐Deoxy‐2′‐C‐methyluridine and (2′R)‐2′‐deoxy‐2′‐C‐methyluridine were incorporated in the 3′‐overhang region of the sense and antisense strands and in positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla luciferase, whereas (2′S)‐2′‐deoxy‐2′‐C‐methylcytidine was incorporated in the 6‐position of the seed region of the same constructions. A dual luciferase reporter assay in transfected HeLa cells was used as a model system to measure the IC₅₀ values of 24 different modified duplexes. The best results were obtained by the substitution of one thymidine unit in the antisense 3′‐overhang region by (2′S)‐ or (2′R)‐2′‐deoxy‐2′‐C‐methyluridine, reducing IC₅₀ to half of the value observed for the natural control. The selectivity of the modified siRNA was measured, it being found that modifications in positions 5 and 6 of the seed region had a positive effect on the ON/OFF activity.     

Synthesis and Characterization of 1,4‐Dimethyl‐5‐Aminotetrazolium 5‐Nitrotetrazolate

1,4‐Dimethyl‐5‐aminotetrazolium 5‐nitrotetrazolate ( 2 ) was synthesized in high yield from 1,4‐dimethyl‐5‐aminotetrazolium iodide ( 1 ) and silver 5‐nitrotetrazolate. Both new compounds ( 1, 2 ) were characterized using vibrational (IR and Raman) and multinuclear NMR spectroscopy (¹H, ¹³C, ¹⁴N, ¹⁵N), elemental analysis and single crystal X‐ray diffraction. 1,4‐Dimethyl‐5‐aminotetrazolium 5‐nitrotetrazolate ( 2 ) represents the first example of an energetic material which contains both a tetrazole based cation and anion. Compound 2 is hydrolytically stable with a high melting point of 190 °C (decomposition). The impact sensitivity of compound 2 is very low (30 J), it is not sensitive towards friction (>360 N). The molecular structure of 1,4‐dimethyl‐5‐aminotetrazolium iodide ( 1 ) in the crystalline state was determined by X‐ray crystallography: orthorhombic, F_ddd, a=1.3718(1) nm, b=1.4486(1) nm, c=1.6281(1) nm, V=3.2354(5) nm³, Z=16, ρ=1.979 g cm⁻¹, R₁=0.0169 (F>4σ(F)), wR₂ (all data)=0.0352.     

Synthesis and Biological Evaluation of Purine 2′‐Fluoro‐2′‐deoxyriboside ProTides as Anti‐influenza Virus Agents

2′‐Fluoro‐2′‐deoxyguanosine has been reported to have potent anti‐influenza virus activity in vitro and in vivo. Herein we describe the synthesis and biological evaluation of 6‐modified 2′‐fluoro‐2′‐deoxyguanosine analogues and their corresponding phosphoramidate ProTides as potential anti‐influenza virus agents. Whereas the parent nucleosides were devoid of antiviral activity in two different cellular assays, the 5′‐O‐naphthyl(methoxy‐L ‐alaninyl) ProTide derivatives of 6‐O‐methyl‐2′‐fluoro‐2′‐deoxyguanosine, 6‐O‐ethyl‐2′‐fluoro‐2′‐deoxyguanosine, and 2′‐deoxy‐2′‐fluoro‐6‐chloroguanosine, and the 5′‐O‐naphthyl(ethoxy‐L ‐alaninyl) ProTide of 6‐O‐ethyl‐2′‐fluoro‐2′‐deoxyguanosine displayed antiviral EC₉₉ values of ～12 μM . The antiviral results are supported by metabolism studies. Rapid conversion into the L ‐alaninyl metabolite and then 6‐modified 2′‐fluoro‐2′‐deoxyguanosine 5′‐monophosphate was observed in enzymatic assays with yeast carboxypeptidase Y or crude cell lysate. Evidence for efficient removal of the 6‐substituent on the guanine part was provided by enzymatic studies with adenosine deaminase, and by molecular modeling of the nucleoside 5′‐monophosphates in the catalytic site of a model of ADAL1, thus indicating the utility of the double prodrug concept.     

Synthesis and Characterization of 3,4,5‐Triamino‐1,2,4‐Triazolium 5‐Nitrotetrazolate

3,4,5‐Triamino‐1,2,4‐triazolium 5‐nitrotetrazolate ( 2 ) was synthesized in high yield from 3,4,5‐triamino‐1,2,4‐triazole (guanazine) ( 1 ) and ammonium 5‐nitrotetrazolate. The new compound 2 was characterized by vibrational (IR and Raman) and multinuclear NMR spectroscopy (¹H, ¹³C, ¹⁵N), elemental analysis and single crystal X‐ray diffraction (triclinic, P(‐1), a=0.7194(5), b=0.8215(5), c=0.8668(5) nm, α=75.307(5), β=70.054(5), γ=68.104(5)°, V=0.4421(5) nm³, Z=2, ϱ=1.722 g cm⁻¹, R₁=0.0519 [F>4σ(F)], wR₂(all data)=0.1154). The ¹⁵N NMR spectrum and X‐ray crystal structure (triclinic, P‐1, a=0.5578(5), b=0.6166(5), c=0.7395(5) nm, α=114.485(5)°, β=90.810(5)°, γ=97.846(5)°, V=0.2286(3) nm³, Z=2, ϱ=1.658 g cm⁻¹, R₁=0.0460 [F>4σ(F)], wR₂(all data)=0.1153) of 1 were also determined.     

Polymerization of 4‐(4′‐N‐1,8‐naphthalimidophenyl)‐1,2,4‐triazolidine‐3,5‐dione with diisocyanates

4‐(4′‐Aminophenyl)‐1,2,4‐triazolidine‐3,5‐dione ( 1 ) was reacted with 1,8‐naphthalic anhydride ( 2 ) in a mixture of acetic acid and pyridine (3 : 2) under refluxing temperature and gave 4‐(4′‐N‐1,8‐naphthalimidophenyl)‐1,2,4‐triazolidine‐3,5‐dione ( NIPTD ) ( 3 ) in high yield and purity. The compound NIPTD was reacted with excess n‐propylisocyanate in N,N‐dimethylacetamide solution and gave 1‐(n‐propylamidocarbonyl)‐4‐[4′‐(1,8‐naphthalimidophenyl)]‐1,2,4‐triazolidine‐3,5‐dione ( 4 ) and 1,2‐bis(n‐propylamidocarbonyl)‐4‐[4′‐(1,8‐naphthalimidophenyl)]‐1,2,4‐ triazolidine‐3,5‐dione ( 5 ) as model compounds. Solution polycondensation reactions of monomer 3 with hexamethylene diisocyanate ( HMDI ), isophorone diisocyanate ( IPDI ), and tolylene‐2,4‐diisocyanate ( TDI ) were performed under microwave irradiation and conventional solution polymerization techniques in different solvents and in the presence of different catalysts, which led to the formation of novel aliphatic‐aromatic polyureas. The polycondensation proceeded rapidly, compared with conventional solution polycondensation, and was almost completed within 8 min. These novel polyureas have inherent viscosities in a range of 0.06–0.20 dL g^?1 in conc. H₂SO₄ or DMF at 25°C. Some structural characterization and physical properties of these novel polymers are reported. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2861–2869, 2003     

Synthesis and Evaluation of 1‐(1‐(Benzo[b]thiophen‐2‐yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase

Thirty two analogues of phencyclidine were synthesised and tested as inhibitors of trypanothione reductase (TryR), a potential drug target in trypanosome and leishmania parasites. The lead compound BTCP ( 1 , 1‐(1‐benzo[b]thiophen‐2‐yl‐cyclohexyl) piperidine) was found to be a competitive inhibitor of the enzyme (K_i=1 μM ) and biologically active against bloodstream T. brucei (EC₅₀=10 μM ), but with poor selectivity against mammalian MRC5 cells (EC₅₀=29 μM ). Analogues with improved enzymatic and biological activity were obtained. The structure–activity relationships of this novel series are discussed.     

Non‐Isothermal Kinetic Study of the Thermal Decomposition of Melamine 3‐Nitro‐1,2,4‐triazol‐5‐one Salt

Study on thermal behavior of 3‐nitro‐1,2,4‐triazol‐5‐one (NTO) salts was required to obtain important data for application purposes. These compounds have been shown to be useful intermediates for gun propellant ingredients, high energetic ballistic modifiers for solid propellants and other potential applications. In this paper, thermal decomposition and non‐isothermal kinetics of melamine 3‐nitro‐1,2,4‐triazol‐5‐one salt (MNTO) were studied under non‐isothermal conditions by DSC and TG methods. The kinetic parameters were obtained from analysis of the DSC and TG curves by Kissinger and Ozawa methods. The critical temperature of thermal explosion (T_b) was 574 K. The results show that MNTO is thermally more stable than NTO when compared in terms of the critical temperature of thermal explosion. Finally, the values of ΔS^#, ΔH^#, and ΔG^# of its decomposition reaction were calculated.