Syntheses of substituted 1-methyl-2-(1,3,4-thiadiazol-2-yl)-4-nitropyrroles and 1-methyl-2-(1,3,4-oxadiazol-2-yl)-4-nitropyrroles

Starting from readily available ethyl-4-nitropyrrole-2-carboxylate ( 1 ), substituted 1-methyl-2-(1,3,4-thiadiazol-2-yl)-4-nitropyrroles and 1-methyl-2-(1,3,4-oxadiazol-2-yl)-4-nitropyrroles were prepared. The reaction of 1 with diazomethane gave ethyl 1-methyl-4-nitropyrrole-2-carboxylate ( 2 ). Reaction of compound 2 with hydrazine hydrate afforded the corresponding hydrazide 3 . The reaction of 3 with formic acid yielded 1-(1-methyl-4-nitropyrrole-2-carboxyl)-2-(formyl)hydrazine ( 7 ). Refluxing of the latter with phosphorus pentasulfide in xylene yielded compound 6 in 40% yield. Reaction of compound 7 with phosphorus pentoxide afforded compound 9 . Reaction of compound 3 with 1,1′-carboxyldiimidazole in the presence of triethylamine yielded 2-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-oxadiazoline-4(H)-5-one ( 11 ). Refluxing compound 3 with cyanogen bromide in methanol gave compound 12 . Compound 13 could be obtained through the reaction of compound 3 with carbon disulfide in basic medium. Alkylation of compound 13 afforded the correspanding alkylthio derivative 14 . Reaction of 1-methyl-4-nitropyrrole-2-carboxylic acid ( 15 ) with thiosemicarbazide and phosphorus oxychloride gave 2-amino-5-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazole ( 16 ). Sandmeyer reaction of compound 16 yielded 2-chloro-5-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazole ( 17 ). Refluxing of the latter with thiourea afforded 2-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazoline-4(H)-5-thione ( 18 ). Alkylation of compound 18 gave the corresponding alkylthio derivative 19 . Oxidation of the latter with hydrogen peroxide in acetic acid yielded 2-(1-methyl-4-nitro-2-pyrrolyl)-5-methylsulfonyl-1,3,4-thiadiazole ( 20 ).     

Synthesis of 2-and 6-chloro-3-(5-methyl-1,3,4-oxadiazol-2-yl)pyridines

A convenient synthesis of 2- and 6-chloro-3-(5-methyl-1,3,4-oxadiazol-2-yl)pyridines, 3 and 10 , utilizing the readily available amide 7 is described. Incorporation of the 3-t-butylamino-2-hydroxypropoxy side chain onto 3 provided 2 , a potential bioisostere of 1 . The antihypertensive activities of 2 and 12 were evaluated in the spontaneously hypertensive rat model.     

N-1,3,4-(口恶)二唑基-N′-呋喃甲酰基硫脲的合成及杀菌活性研究

将呋喃环、1,3,4-(口恶)唑环2个杂环同时引入到酰基硫脲中,合成了10个未见报道的酰基硫脲类化合物. 所有化合物的结构均经元素分析、红外光谱、核磁共振氢谱和质谱确认. 抑菌法生物活性测试表明,各目标产物对黄瓜灰霉病菌的抑制效果较好,最高可达97%.     

3-（3-乙酰基-5-芳氧亚甲基-2,3-二氢-1,3,4-噁二唑-2-基）色酮类化合物的合成

3-（3-乙酰基-5-芳氧亚甲基-2;3-二氢-1;3;4-噁二唑-2-基）色酮类化合物的合成;噁二唑啉;色酮;合成     

Nitroimidazoles X . Syntheses of substituted 2-(1-methyl-5-nitro-2-imidazolyl)quinolines

Reduction of substituted-2-nitrobenzaldehyde (1) afforded substituted-2-aminobenzaldehyde (2) . Reaction of compound 2 with 2-acetyl-1-methyl-5-nitroimidazole (3) under basic conditions afforded substituted 2-(1-methyl-5-nitro-2-imidazolyl)quinolines 4 . Reaction of compound 4 (R = X) with hydrogen peroxide in acetic acid afforded compound 5 which was transformed to compound 6 with phosphorus oxychloride.     

Nitroimidazoles. IX. Synthesis of 2-acetyl-1-methyl-5-nitroimidazole

Manganese dioxide oxidation of 2-hydroxymethyl-1-methyl-5-nitroimidazole (6) gave 1-methyl-5-nitroimidazole-2-carboxaldehyde (7) in high yield. Reaction of diazomethane with 7 afforded the title compound 1 in low yield. Treatment of ethyl acid malonate with two equivalents of isopropylmagnesium bromide in THF and subsequent addition to 1-methyl-5-nitroimidazole-2-carbonylimidazolide (12) yielded ethyl (1-methyl-5-nitroimidazole-2-carbonyl)acetate (10) in 70% yield. Hydrolysis and decarboxylation of compound 10 gave the desired compound 1 in 97% yield.     

新型1-(1,3,5-三嗪-6-基)-3-甲基-4-(5-苯基-1,3,4-噁二唑-2-基)吡唑的合成及活性评价

设计合成了18个以吡唑桥连1,3,4-噁二唑和1,3,5-三嗪的新型多杂环分子[7A(a~f),7B(a~f)和7C(a~f)];通过红外光谱(IR)、核磁共振波谱(NMR)和高分辨质谱(HRMS)等对目标分子进行了结构表征;评价了目标分子对蛋白酪氨酸磷酸酯酶1B(PTP1B)和细胞分裂周期25磷酸酯酶B(Cdc25B)的抑制活性.结果表明,所有目标分子对PTP1B和Cdc25B均有较好的抑制活性,其中,9个目标分子表现出优异的PTP1B和Cdc25B抑制效果,IC50值低于齐墩果酸(PTP1B抑制活性测试参照物)和正钒酸钠(Cdc25B抑制活性测试阳性参照物),有望成为潜在的PTP1B和Cdc25B抑制剂.     

Synthesis of 3-(5-Aryl-1,3,4-oxadiazol-2-yl)chromones

A general method was proposed for the synthesis of 3-(5-aryl-1,3,4-oxadiazol-2-yl)chromones starting from 3-formylchromone. This aldehyde yields acylhydrazones, from which the corresponding unstable nitrile imines are generated. These intermediates undergo intramolecular 1,3-dipolar cycloaddition.     

Synthesis of 3-(5-Aryl-1,3,4-oxadiazol-2-yl)chromones

A general procedure was proposed for the synthesis of 3-(5-aryl-1,3,4-oxadiazol-2-yl)chromones by reaction of 3-formylchromone with aroylhydrazines, transformation of the corresponding acylhydrazones into 1,3-dipoles by the action of bromine in the presence of sodium acetate, and intramolecular ring closure.     

Synthesis and antimycobacterial screening of new N-(4-(5-aryl-3-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrazol-1-yl)phenyl)-4-amide derivatives

This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-(4-(5-aryl-3-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrazol-1-yl)phenyl)-4-amide derivatives(8a–x). The antitubercular activity of the compounds against Mycobacterium tuberculosis H37Rv(MTB) revealed that 2-chloro-N-(4-(5-(4-chlorophenyl)-3-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrazol-1-yl)phenyl)benzamide(8n) is the most promising lead molecule with a MIC of1.56 mg/m L, while the corresponding unsubstituted benzamide derivative(8o) is the next most active molecule with a MIC of 3.13 mg/m L. Interestingly, the pyrazole intermediate 5b containing chlorophenyl and N-acylcarbohydrazide substituents also showed significant activity(MIC = 3.13 mg/m L). Further, the active molecules did not show toxicity against a normal NIH 3T3 cell line, signifying their suitability for further drug development.     

超声辐射下合成1-[(未)取代苯酰基-3-[5-(1-苯基-3-甲基-5-氯吡唑-4-基)-1,3,4-噻二唑-2-基]-硫脲

1-苯基-3-甲基-5-氯吡唑-4-甲酸与氨基硫脲在三氯氧磷中反应得到2-氨基-5-(1-苯基-3-甲基-5-氯吡唑-4-基)-1,3,4-噻二唑(1), 然后分别采用超声辐射法和常规加热法与(未)取代苯甲酰基异硫氰酸酯(2)反应合成了一系列未见报到的1-[(未)取代苯酰基-3-[5-(1-苯基-3-甲基-5-氯吡唑-4-基)-1,3,4-噻二唑-2-基]-硫脲(3a～3j). 化合物的结构经元素分析, IR, ¹H NMR确证.     

Synthesis and functionalization of the 3-(1,3,4-oxadiazol-2-yl)-1h-indoles

A modified method is proposed for the preparative synthesis of 3-(1,3,4-oxadiazol-2-yl)-1H-indoles in high yield. We are the first to demonstrate the functionalization of this heterocyclic system by alkylation. In particular, syntheses are reported for [3-(1,3,4-oxadiazol-2-yl)-1H-indol-1-yl]acetic acids and their amide derivatives.     

Spectral properties of (5-phenyl-1,3,4-oxadiazol-2-yl)-7-hydroxycoumarin (POHC)

The electronic absorption, emission and excitation spectra of POHC were measured in different solvents and are affected by solvent polarity. The fluorescence quantum yield of POHC decreases with increasing Richardt and Dimorth solvent parameter (E(T)) value of the solvent. In dilute solutions POHC is almost totally present in its protonated nitrogen tautomer form. The deprotonation is a reversible process. A shoulder in the absorption spectra at approximately 473 nm indicates the presence of a portion of the tautomer (s) that disappears on lowering the temperature. Molecular oxygen acts as a quencher with quenching rate constant of 1.8 x 10(10) M(-1) s(-1) in DMF. Energy transfer from POHC to rhodamine 6G in ethanol was also studied. POHC is relatively photostable in ethanol (phic approximately 1.7 x 10(-4)). Quantum chemical calculations were carried out and correlated to experimental observations.     

新型N-(5-烷基-1,3,4-噻二唑-2-基)-11[(杂芳基)甲基]-5-甲基-1H-1,2,3-三唑基-4-甲酰胺的合成与生物活性

为了寻找新型高效低毒的农药先导化合物,采用1-[(杂芳基)甲基]-5-甲基-1H-1,2,3-三唑基-4-甲酰氯与2-氨基-5-烷基-1,3,4-噻二唑的缩合反应,合成了8种未见文献报道的目标化合物,其结构经IR,1H NMR和元素分析确证,部分化合物还经MS的进一步证实.初步的生物活性测试结果表明,部分目标化合物在100 mg/L浓度下对双子叶植物(油菜)显示出中等的除草活性和一定程度的杀虫活性(250 mg/L).     

[5-(芳亚甲基氨基)-1,3,4-噻二唑-2-基]硫乙酰芳胺的合成及 生物活性研究

在K2CO3存在下利用聚乙二醇-400 (PEG-400)作相转移催化剂, 于固-液相转移催化条件下, 通过5-芳亚甲基氨 基-2-巯基-1,3,4-噻二唑与氯乙酰芳胺的硫烷基化反应, 合成了16个未见文献报道的[5-(芳亚甲基氨基)-1,3,4-噻二唑-2-基]硫乙酰芳胺衍生物. 经元素分析, FT-IR,1H NMR和13C NMR确证了其结构. 生物活性实验结果表明, 部分化合物对小麦幼苗的生长具有明显的植物生长调节活性, 并对枯草杆菌具有一定的抑制活性.