Tautomerism in 6-Arylpyridazin-3(2H)-thiones and some of their reactions

6-Arylpyridazin-3(2H)-thiones exist mainly, if not entirely, in the thione form ( 1 ). This was shown by spectroscopic studies on some of these compounds and their substitution products either on the nitrogen or on the sulphur [in the mercaptopyridazine form ( 2 )]. However, the reacting tautomer of these compounds was found to be dependent upon the basicity of the reaction medium. Selected 6-arylpyridazin-3(2H)-thione derivatives react with formaldehyde and sec-amines to give N-2-aminomethyl derivatives ( 8 ) [thione form ( 1 )]. On the other hand oxidation and alkylation reactions gave disulphides ( 10 ) and S-alkyl derivatives ( 7 ) [mercapto form ( 2 )].     

Action of Grignard Reagents on N-Arylcitraconimides and Substituted hydroxypyrrolinones

Arylmagnesium bromides react with N-arylcitraconimides at room temperature, to give 5-aryl-5-hydroxy-3-methyl-N-aryl-2-pyrrolinones 1 , which can be considered as the cyclic form of cis-β-aroyl-α-methyl-N-arylacrylamides, as the sole product. The structure assignments are based on infrared and electronic spectra and also on the synthesis of these compounds by the isomerisation of the corresponding trans-isomers 3 which are synthesised by the reaction between trans-β-aroyl acryloyl chlorides and amines. Arylmagnesium halides react with 1 to give β-aroyl-β-aryl-α-methyl-N-arylpropionamides 5 as the sole product in most cases. However, in few cases a poor yield of an isomeric substance 5′ is obtained in addition to the predominating isomers. 5a, c, e and j are also obtained by the action of 3 moles of the suitable Grignard reagent on one mole of N-arylcitra-conimide. Structural assignments are based on infrared, electronic and nuclear magnetic resonance spectra.     

Action of grignard reagents on 6-(α-styryl)pyridazin-3(2H)-ones; synthesis of some 4-Substituted 6-(α-Styryl)-pyridazin-3(2H)-ones

6(α-Styryl)pyridazin-3(2H)-ones ( 1a – e ) reacted with phenylmagnesium bromide and/or methylmagnesium iodide to give the 1,4-addition products, 4-phenyl and/or 4-methyl-6-(α-styryl)pyridazin-3(2H)-ones ( 3a–e ). The structures assigned to the products are established by electronic and infrared spectroscopy and by synthesis of authentic samples in most cases.     

新型2-烷氧基-4(3-H)-喹唑啉酮类杀菌剂的QSAR研究

采用Cerius2软件中的主成分分析法和Var.Jarvis-Patrick聚类方法对新型2-烷氧基-4(3H)-喹唑啉酮类化合物进行分类,然后用遗传算法(GFA)建立杀菌活性与优选的分子结构描述符之间的构效关系(QSAR)模型,所建模型均通过显著性检验,交叉验证系数(CV-r2)最大达0.996,具有良好的预测可靠性.结果表明:分子空间性质、给电子能力的大小和热力学性质等是影响活性的主要因素,并用所建最优模型预测了5个经典生物电子等排取代物的杀菌活性.该研究可为新型杀菌剂先导化合物的设计与合成提供理论指导.     

2-溴-6-氯-3(2H)-苯并呋喃酮的合成

2-溴-6-氯-3(2H)-苯并呋喃酮是合成具有稠杂环结构杀虫剂的中间体.从4-氯水杨酸开始,运用新颖的方法,经过酯化、成醚、水解、闭环、溴代5步化学反应得到产物,总收率19%.产品结构经质谱、核磁共振氢谱确认正确.     

6—取代苯基—3（2H）—哒嗪酮的合成

以茴香醚为原料经Friedel－Crafts反应,环合反应以及脱氢反应等合成了6－取代苯基－3（2H（）－哒嗪酮类化合物。     

The synthesis and some reactions of novel pyridine-2(1H)-thiones

The use of methyl 3-mercaptopropionate for the conversion of halogenated pyridines to pyridine thiones and thiols is described, and limitations of the reaction discussed. S-Alkylation and oxidation reactions of the products from these reactions are reported.     

Synthesis and Anticancer Activity of Mitotic-Specific 3,4-Dihydropyridine-2(1H)-thiones

Most anticancer drugs target mitosis as the most crucial and fragile period of rapidly dividing cancer cells. However the limitations of classical chemotherapeutics drive the search for new more effective and selective compounds. For this purpose structural modifications of the previously characterized pyridine analogue (S1) were incorporated aiming to obtain an antimitotic inhibitor of satisfactory and specific anticancer activity. Structure-activity relationship analysis of the compounds against a panel of cancer cell lines allowed to select a compound with a thiophene ring at C5 of a 3,4-dihydropyridine-2(1H)-thione (S22) with promising antiproliferative activity (IC₅₀ equal 1.71 ± 0.58 µM) and selectivity (SI = 21.09) against melanoma A375 cells. Moreover, all three of the most active compounds from the antiproliferative study, namely S1, S19 and S22 showed better selectivity against A375 cells than reference drug, suggesting their possible lower toxicity and wider therapeutic index. As further study revealed, selected compounds inhibited tubulin polymerization via colchicine binding site in dose dependent manner, leading to aberrant mitotic spindle formation, cell cycle arrest and apoptosis. Summarizing, the current study showed that among obtained mitotic-specific inhibitors analogue with thiophene ring showed the highest antiproliferative activity and selectivity against cancer cells.     

Recyclization of 2-iminocoumarin-3-carbonitriles with 2-aminothiobenzamide: a new synthetic route to substituted 2-(2-iminocoumarin-3-yl)quinazoline-4(3H)-thiones

The reaction of 2-aminothiobenzamide with either 2-iminocoumarin-3-carbonitrile or 2-iminocoumarin-3-thiocarboxamides has been studied. It has been established that in both cases, 2-(2-iminocoumarin-3-yl)quinazoline-4(3H)-thiones are formed as the result of a two-step procedure. The reactions of 2-(2-iminocoumarin-3-yl)quinazoline-4(3H)-thiones with arylamines and alkylating agents have been studied.     

Action of Grignard reagents on thiophthalic anhydride, 3-benzal-2-thiophthalide, 3-p-chloro- and 3-p-methoxybenzalphthalides

Thiophthalic anhydride 1 reacts with the GRIGNARD reagents 2a – e (1:1 mol.) to give the corresponding 3-aryl(alkyl)-3-hydroxy-2-thiophthalides 3a – e . The interaction of 1 with 2c and f (1:2 mol.) yields the corresponding 1,2-diaroylbenzene derivatives 4 . On the other hand, 1 reacts with 2b (1:2 and 1:3 mol.) to give 5 and 6 , respectively. When 3-benzal-2-thiophthalide 7a and 3-p-chlorobenzalphthalide 7b are allowed to react with the GRIGNARD reagents 2c – f , the corresponding indenone derivatives 8 are obtained. On the other hand, the reaction of 7a and b with 2b (1:2 mol.) yields 6 and 9 , respectively. 7a and p-methoxybenzalphthalide 7c react with 2b (1:1 mol.) to give 5 and 10 ( a and b ). The constitution of the products has been investigated by means of IR and UV spectra.     

配合物Ni(C_6H_6NO_3S)_2(H_2O)_4的合成、表征及热稳定性

用常温挥发法合成了一个新颖的单核配合物Ni(C6H6NO3S)2(H2O)4,并利用红外光谱、元素分析、热重分析及X-射线单晶衍射法对其结构进行了表征。结果表明,该配合物晶体属于单斜晶系,P121/n1空间群,晶胞参数为:a=1.191 2 nm,b=0.633 nm,c=1.224 nm,β=108.936°,Z=2,R1=0.027 1,wR2=0.100 7。在标题配合物中,每个Ni2+与4个H2O分子的氧原子及来自两个邻氨基苯磺酸的两个氮原子配位,形成一个畸变的八面体构型。在该配合物中,磺酸基的氧原子没有配位,这表明在该体系下,H2O的配位性能优于磺酸基氧原子。     

Synthesis of polyfunctionally substituted pyridine-2-(1H)-thiones containing a sulfone moiety

1-Phenyl-2-(phenylsulfonyl)ethanone (1) reacts with DMFDMA to give enamine 2, which upon treatment with cyanothioacetamide affords 3-cyano-5-benzenesulfonyl-4-phenylpyridine-2(1H)-thione (4), a compound that can also be obtained by the reaction of 1-benzenesulfonyl-1-benzoyl-2-ethoxyethene (3) with cyanothioacetamide. The reaction of 2-thiocarbamoylacetamide (8a) and N-phenyl-2-thiocarbamoylacetamide (8b) with 3-aryl-2-benzenesulfonylacrylonitrile (9a– c) affords 10a–f. The methylation of 10d–f with methyl iodide results in the formation of S-methyl derivatives (12a–c). Compound 12c can be obtained by the reaction of 13 with 9c.     

Action of Nucleophilic Reagents on Wool

Degradation of the disulphide bonds in wool caused by the action of nucleophilic reagents has been studied. The simultaneous formation of lanthionine and lysinoalanine on treatment with NaOH supports a mechanism entailing β-elimination and the formation of an aminoacrylic acid residue as an intermediate. Treatment with KCN gives only lanthionine, thus excluding a β-elimination mechanism; an S_n2 mechanism is suggested. The formation of lanthionine and lysinoalanine on treatment with Na₂S rules out a simple S_n2 mechanism; it is suggested that a β-elimination and an S_n2 mechanism operate simultaneously. The increase in the extent of reaction in the presence of organic solvents (acetone, ethanol, propanol, and pyridine) may be due to the breakage of hydrophobic bonds; this has been studied by using different acetone: water mixtures in the NaOH treatment.     

配合物La（C6H5CHOHC00）3（phen）（H2O）的合成

用苯羟基乙酸、邻菲罗啉与稀土的硝酸盐为原料合成了配合物La(C_6H_5CHOHCOO)_3(phen)(H_2O),通过元素分析、红外光谱、核磁共振等测试手段,确定了配合物的组成和结构,并通过热重分析对其热性质进行了表征。结果表明,配合物中邻菲罗啉以双齿螯合方式配位,而苯羟乙酸则以桥联或单齿方式参与配位。     

Calcium(II)(3) (3,5-Diisopropylsalicylate)(6)(H(2)O)(6) Activates Nitric Oxide Synthase: An Accounting for its Action in Decreasing Platelet Aggregation

Purposes of these studies were first; to determine whether or not Calcium(II)(3) (3,5- diisopropylsalicylate)(6)(H(2)O)(6) [Ca(II)(3)(3,5-DIPS)(6)], a lipophilic calcium complex, could decrease activated-platelet aggregation, and second; to determine whether or not it is plausible that Ca(II)(3)(3,5-DIPS)(6) decreases activated-platelet aggregation by facilitating the synthesis of Nitric Oxide (NO) by Nitric Oxide Synthase (NOS). The influence of Ca(II)(3)(3,5-DIPS)(6) on the initial rate of activated-platelet aggregation was determined by measuring the decrease in rate of increase in transmission at 550 nm for a suspension of Thrombin-CaCl(2) activated platelets following the addition of 0, 50, 100, 250, or 500 muM Ca(II)(3)(3,5-DIPS)(6). To establish that the Ca(lI)(3)(3,5- DIPS)(6)-mediated decrease in aggregation was due to activation of NOS, the effect of L-NMMA, an inhibitor of NOS, on the inhibition of platelet aggregation by Ca(II)(3)(3,5-DIPS)(6) was determined using a suspension of activated platelets contaimng 0 or 250 muM Ca(II)(3)(3,5-DIPS)(6) without or with 1 mM L-NMMA. An in vitro Bovine Brain NOS reaction mixture, containing CaCl(2) for the activation of Phosphodiesterase-3' ,5'-Cyclic Nucleotide Activator required for the activation of NOS, was used to determine whether or not Ca(II)(3)(3,5-DIPS)(6) could be used as a substitute for the addition of Ca. The decrease in absorbance at 340 nm, lambda maximum for NADPH, was measured to determine NOS activity following the addition of NOS to the complete reaction mixture containing either CaCl(2), Ca(II)(3)(3,5-DIPS)(6), or neither Ca compound. Increasing the concentration of Ca(II)(3)(3,5-DIPS)(6) caused a concentration related decrease in activated platelet aggregation. The addition of L-NMMA to activated platelets, in the absence of Ca(II)(3)(3,5-DIPS)(6), caused a 129% increase in initial rate of platelet aggregation. The initial rate of platelet aggregation decreased 74% with the addition of 250 muM Ca(II)(3)(3,5-DIPS)(6) and the addition of L-NMMA plus 250 muM Ca(II)(3)(3,5-DIPS)(6) caused a 197% decrease in initial rate of aggregation compared to the initial rate observed width the presence of 1 mM L-NMMA alone. There was only a small, 27%, increase in initial rate of 0.4 mM NADPH oxidation when 0.9 mM CaCl(2) was added to the NOS reaction mixture in comparison to the initial rate of NADPH oxidation with no addition of CaCI(2). Addition of an equivalent amount of Ca in the form of Ca(II)(3)(3,5-DIPS)(6), 333 muM, caused a 37% increase in initial rate of NADPH oxidation compared to the addition of 0.9 mM CaCl(2). Addition of increasing concentrations of L-NMMA plus 0.9 mM CaCl(2) or 333 muM Ca(II)(3)(3,5-DIPS)(6) to the NOS reaction mixture caused a concentration related increase in initial rate of NADPH oxidation. Addition of L-NMMA while expected to decrease NADPH oxidation actually increased the rate of NADPH oxidation. Additions of 133 muM or 267 muM Ca(II)(3)(3,5- DIPS)(6) also caused concentration related increases in initial rate of NADPH oxidation in the presence of 113 muM L-NMMA. However, the addition of 533 muM Ca(II)(3)(3,5-DIPS)(6) caused a dramatic decrease in initial rate of NADPH oxidation by NOS. It is concluded that: 1) Ca(II)(3)(3,5- DIPS)(6) activates platelet NOS in preventing platelet aggregation, 2) in vitro NOS activity can be observed spectrophotometrically by following the consumption of NADPH as a decrease in absorbance at 340 nm, 3) Ca(II)(3)(3,5-DIPS)(6) plays a role in enhancing Bovine Brain NOS activity resulting in an increased rate of NADPH oxidation by NOS, 4) Ca(II)(3)(3,5-DIPS)(6) is a useful form of Ca in activating NOS and superior to CaCl(2) with regard to the facilitation of a NADPH oxidation, and 5) L-NMMA stimulates Bovine Brain NOS activity rather than causing an inhibition of this enzyme and must serve as a reducible substrate for Bovine Brain NOS.     

[Nd(6-OHnicH)_3(H_2O)_6]_n配合物的合成和晶体结构研究

在水热反应条件下,采用6-羟基吡啶-3-甲酸(6-OHnicH)与稀土金属离子钕合成了标题化合物。运用元素分析、红外光谱、X-射线衍射等进行了表征。X-射线衍射结果表明:该配合物属于三斜晶系,空间群是P-1,晶胞参数为:a=7.1693(8),b=10.3227(12),c=16.7831(19),α=73.3000(10)°,β=88.0070(10)°,γ=88.2180(10)°,Z=2。该配合物最终通过分子间氢键作用堆积为三维网状结构。