Molecular and crystal structures of 6-substituted 4-phenylquinazoline 3-oxides and 2,2,6-trimethyl-4-phenyl-1,2-dihydroquinazoline

Single crystal X-ray diffraction (XRD) has been employed for the determination of crystal and molecular structures of three 6-substituted 4-phenylquinazoline 3-oxides. Characteristic features of the structures have been revealed, intermolecular interactions have been considered.     

Electrochemical behaviour of quinazoline in amphiprotic media

The electrochemical behaviour of quinazoline in aqueous methanolic solutions has been studied in detail. In acid solutions two single-electron waves of equal height are obtained whereas in neutral solutions a single two-electron wave is observed. Quinazoline gets reduced to tetrahydroquinazoline in alkaline media and very interestingly gives reverse cathodic peaks during cyclic voltammetric experiments. The polarographic waves are diffusion-controlled and irreversible on the basis of the usual criteria. Based on the results obtained, reduction schemes are given for quinazoline in various buffered media. A comparison of the electrochemical behaviour, between quinazoline and 4-(2-thienyl)quinazoline (4-TQ) has been attempted.

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Das elektrochemische Verhalten von Chinazolin in amphiprotischen Medien

Zusammenfassung Das elektrochemische Verhalten von Chinazolin in wäßrigen methanolischen Lösungen wurde im Detail untersucht. In sauren Lösungen wurden zwei Einelektronenwellen gleicher Höhe erhalten, währenddessen in neutralen Lösungen eine einzige Zweielektronenwelle beobachtet wurde. Chinazolin wird in alkalischem Medium zu Tetrahydrochinazolin reduziert und ergibt interessanterweise kathodische Umkehrpeaks während cyclischer voltammetrischer Experimente. Die polarographischen Wellen sind diffusionskontrolliert und nach den üblichen Kriterien irreversibel. Aufgrund dieser Ergebnisse werden Reduktionsschemata für Chinazolin in verschiedenen Puffermedien angegeben. Es wird ein Vergleich zwischen dem elektrochemischen Verhalten von Chinazolin und 4-(2-Thienyl)-chinazolin (4-TQ) angestellt.

     

Condensed isoquinolines 26. Oxidation reactions of 6,11-dihydro-13H-isoquino-[3,2-<Emphasis Type="Italic">b</Emphasis>]quinazolin-13-one derivatives

Oxidation of the hydrobromide of 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one with dimethyl sulfoxide leads to 11-hydroxy-11H-isoquino[3,2-b]quinazoline-6,13-dione, and with hydrogen peroxide to the hydrobromide of 2-[(4-oxo-3,4-dihydro-2-quinazolinyl)carbonyl]benzoic acid. Salts of 5-and 6-alkyl-substituted isoquino[3,2-b]quinazolines are readily oxidized on boiling in nitrobenzene, which leads to aromatization of the isoquino[3,2-b]quinazoline system to 5-methyl-13-oxo-5H,13H-isoquino[ 3,2-b]quinazolinium perchlorate and 6-benzyl-13H-isoquino[3,2-b]quinazolin-13-one. The structures of the dehydrogenation products were established from ¹H NMR and UV spectra. The interaction of the obtained compounds with NaBH₄ has been studied. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1833–1840, December, 2007.     

CuCl-catalyzed one-pot synthesis of 5,6-dihydropyrazolo[1,5-c]quinazolines

A simple and efficient procedure for the preparation of 5,6-dihydropyrazolo[1,5-c]quinazolines via CuCl-catalyzed tandem reaction of 5-(2-bromoaryl)-1H-pyrazoles with aldehydes and aqueous ammonia under nitrogen atmosphere has been developed. The usefulness of this novel methodology was showcased by its successful application in the preparation of a potential Eg5 inhibitor.     

新型双腙基喹唑啉类衍生物的合成及其抑菌活性

以邻氨基苯甲酸为起始原料,设计并合成了17个新型的双腙基喹唑啉类衍生物,其结构经1H NMR,13C NMR,IR,MS和元素分析表征.初步生物活性测试结果表明,部分化合物对小麦赤霉菌、辣椒枯萎菌和苹果腐烂菌有一定的抑制活性.     

4-硫醚基喹唑啉类化合物的合成及抑菌活性研究

以4-氯喹唑啉和巯基化合物为原料, 丙酮作溶剂, 碳酸钾作缚酸剂, 合成了7个新型4-硫醚基喹唑啉类化合物. 采用¹H NMR, ¹³C NMR, IR及元素分析对目标化合物的结构进行了表征. 生物活性测试表明, 化合物1d在50 μg•mL^－1 药剂浓度下对小麦赤霉病菌、辣椒枯萎病菌、苹果腐烂病菌的抑菌活性分别达到69.5%, 71.9%和70.8%, EC₅₀分别为25.88, 17.08和28.77 μg•mL^－1.     

Condensed isoquinolines 25. Alkylation of 6,11-dihydro-13H-isoquino[3,2-<Emphasis Type="Italic">b</Emphasis>]quinazolin-13-one

Interaction of 6,11-dihydro-13H-isoquino[2,3-b]quinazolin-13-one with alkylating agents occurs at two positions depending on their nature and the reaction conditions-at C₍₆₎ or N₍₅₎. Fusion with methyl tosylate leads to 5-methyl-13-oxo-6,13-dihydro-11H-isoquino[3,2-b]quinazolin-5-ium salts, while interaction with benzyl halides in the presence of i-PrONa gave 6-benzyl-and 6,6-dibenzyl-6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-ones. Alkylation with olefins led to two types of products. In the case of maleinimides and maleic acid anhydride Michael adducts at C₍₆₎ were formed and in the case of cyanocinnamic acid esters the reaction was accompanied by intramolecular acylation at N₍₅₎ to give 1-aryl-3,9-dioxo-3H,9H,11H-benzo[5,6][1,8]naphthyridino[1,8-ab]quinazoline-2-carbonitrile. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.11, 1698–1708, November 2007.     

Structures of 1,2,3,4-tetrahydro-6H-pyrimido[2,1-b]-quinazolin-6-one and its hydrochloride

C₁₁H₁₁N₃O, m.p. 243°C, P2/n,Z=4,a=5.843(2),b=14.241(3),c=11.102(1) Å, =93.30(2)°,R=0.046; C₁₁H₁₁N₃O·HCl·H₂O, Pca2₁,Z=8,a=18.640(2),b=8.894(2),c=14.404(2)Å,R=0.062. The molecules of the free base are in 1H-tautomeric form. N(1)-H...N(11) hydrogen bonds join molecules of the free base into dimers, which enable tautomeric rearrangement (not observed in this study) also in the solid state without any changes in molecular packing. The quinazoline system deviates slightly from planarity and benzene electrons are partially localized at C(7)–C(8) and C(9)–C(10) bonds as seen from their lengths of about 1.375 Å, while other bonds in the benzene ring are at least 0.02 Å longer.     

6-溴-4-烃硫基喹唑啉类化合物的合成及抑菌活性研究

以6-溴-4-巯基喹唑啉和卤代烃为原料, 用相转移催化法合成了10个新的6-溴-4-烃硫基取代喹唑啉类化合物. 化合物经1H NMR, 13C NMR, IR及元素分析证明其结构. 初步生物活性试验结果表明, 在50 mg&#8226;L－1浓度下, 化合物6g对小麦赤霉病菌、辣椒枯萎菌、苹果腐烂菌抑制率分别为63.8%, 51.9%, 55.1%, 与对照药剂恶霉灵抑制活性相当.     

抗癌性吲哚喹唑啉衍生物3D-QSAR研究及其分子设计

吲哚喹唑啉衍生物是近年来发现的一类具有良好抗癌活性的化合物. 作者在最近报道的二维定量构效关系(2D-QSAR)的基础上, 采用比较分子力场方法(CoMFA)进一步对该系列化合物进行三维定量构效关系(3D-QSAR)研究, 建立了3D-QSAR的CoMFA模型, 其非交叉验证相关系数r2=0.986, 标准偏差SD=0.084, 统计方差比F=114.6, 交叉验证相关系数q2=0.695, 表明该模型合理、可信, 并具有良好的预测能力. 研究结果表明: (1) 取代基R1的部位上静电效应起主要作用, 并且确保取代基R1的第一个原子具有较大的净正电荷, 对提高化合物的抗癌活性十分重要. 这与2D-QSAR研究结果相一致. (2) 取代基R2的部位上立体效应起主要作用, R2的体积大小要适中. 应用这些规律进行了分子设计, 在理论上获得了一些具有较高抗癌活性的新的吲哚喹唑啉衍生物, 并期待实验证实. 该QSAR的研究结果可为实验工作者合成新药提供理论参考.