四氢异喹啉衍生物的合成及抗真菌活性

目的 寻找新的抗真菌活性化合物。方法 采用Pictet-Spengler法合成四氢异喹啉，再通过氮直接烃化法合成目标化合物，并对目标化合物进行初步的体外抗真菌活性实验。结果 合成了18个新的四氢异喹啉衍生物，利用红外光谱、核磁共振谱进行了结构确认。结论 所合成的18个四氢异喹啉衍生物具有不同程度的抗真菌活性。     

N,N-双取代脲类克鲁斯氏锥体虫半胱氨酸蛋白酶小分子抑制剂的合成及其活性研究

目的寻找克鲁斯氏锥体虫体半胱氨酸蛋白酶Cruzain的小分子抑制剂.方法根据时Cruzain分子结构的计算机模拟设计结果,选用N,N-双取代脲为先导结构,目标化合物的合成采用Curtius重排反应,测定了化合物的体外抑制Cruzain的IC50值.结果设计并合成了21个未见文献报道的双取代脲衍生物,确证了它们的化学结构.结论生物活性测定结果显示,所合成的化合物均有不同程度的抑制Cruzain的活性,其中化合物Ⅳ9和Ⅳ17的活性好于对照药tf-175.Ⅳ8的活性与对照药tf-175相当.     

Microwave-assisted synthesis, hypolipidemic and hypoglycemic activity of some novel 2-(4-(2-Amino-6-(4-substituted phenyl)-pyrimidin-4-yl)-phenoxy)-2-methyl propanoic acid derivatives

A novel series of aminopyrimidines containing the phenoxy isobutyric acid group as a pharmacophore was synthesized using conventional and microwave assisted methods of synthesis. The compounds were synthesized in good yields (70-89%) by the microwave-assisted one-pot protocol in much shorter reaction times. The synthesized compounds were evaluated for their hypolipidemic and hypoglycemic activity by high-fat diet-induced hyperlipidemia and hyperglycemia in male Sprague-Dawley rats. The present investigation showed significant antihyperlipidemic and antihyperglycemic activity for all compounds of the series when compared with the standard drug. Structure-activity relationship (SAR) for the series were developed by comparing total lipid profile data of synthesized compounds with fenofibrate as standard drug.     

2-烯基-4(1H)-喹诺酮的合成及生物活性研究

采用两种方法合成了3个2-烯基-4(1H)-喹诺酮(I～II),其中化合物II是从吴茱萸中分离得到的新化合物,其余2个化合物尚未见文献报道。并对所合成的化合物及中间体进行了初步药理试验,表明有一定的扩张血管和抗菌作用。     

环丙沙星衍生物的合成及抗菌活性研究

目的研究环丙沙星衍生物的合成及其抗菌活性。方法采用2-甲基-5-硝基咪唑、环丙沙星等为原料,通过亲核取代反应合成目的物；测定目的物的抗菌活性。结果设计、合成了9个新化合物,其结构经MS,¹H NMR和元素分析确证。化合物II, IV_C和 IV_D的体内抗菌活性较明显。结论化合物II, IV_C和 IV_D显示了一定的体内抗菌活性,值得进一步研究。     

Malonyl amino acids and their esters as psychoactive agents I

Malonic acid amides were synthesized using different amino acids and their esters. The synthesized compounds were evaluated for their sedative activity on rats. Potentiating effect of all the compounds on pentobarbitone induced sleep on rats was observed. Plasma protein binding studies were also carried out and it was observed that the synthesized compounds have low plasma protein binding as compared to barbiturates.     

新型核苷膦酸酯类化合物的合成及其抗乙肝病毒活性研究

目的设计合成新型核苷膦酸酯类化合物,并进行体外抗乙肝病毒活性评价。方法以不同取代的硫酚与2-氨基-9-[2-[二(2,2,2-三氟乙氧基)膦酰甲氧基]乙基]-6-氯嘌呤进行烃化反应合成目标化合物,化合物结构经1H-NMR和FAB-MS谱确证。采用HepG2.2215细胞进行体外抗乙肝病毒活性评价。结果与结论设计合成了9个核苷膦酸酯类新化合物,这些化合物均有一定的抗乙肝病毒活性。化合物4a、4b的活性强于拉米夫定、阿德福韦酯。苯环上取代基的类型显著影响核苷膦酸酯类化合物抗乙肝病毒活性。     

Antimicrobial activity of a new series of benzimidazole derivatives

Due to antimicrobial importance of benzimidazoles and hydrazones, some benzimidazolehydrazone compounds were synthesized to screen their antimicrobial activity. Structures of the synthesized compounds were elucidated by ¹H-NMR, IR and ES-MS spectral data and elemental analysis. The synthesized benzimidazole-hydrazones exhibited very weak antibacterial activity. However, antifungal activity of some of the synthesized compounds was very notable against Candida species. The compounds displaying important antifungal activity were screened for their toxicity. Artemia salina 96-well assay was used to determine cytotoxicity of the compounds. Tested compounds exhibited toxicity to different extents (LD₅₀ = 126.33−368.72 μg/mL). Nevertheless, determination of 3–14 folds higher LD₅₀ than minimum inhibitory concentration is a significant finding, which demonstrates that the compounds display antifungal activity at non-toxic concentration.     

Synthesis and antimicrobial evaluation of hydrazones derived from 4-methylbenzenesulfonohydrazide in aqueous medium

A series of biologically active N′-substituted-4-methylbenzenesulfonohydrazide derivatives were synthesized by condensation of 4-methylbenzenesulfonohydrazide and aromatic carbonyl compounds in the presence of polystyrene sulfonic acid in aqueous medium. The synthesized compounds were characterized by IR, NMR and mass spectra. The compounds have been evaluated for antimycobacterial, antibacterial and antifungal activities.     

雌激素哌嗪类衍生物的合成及其促骨生长活性

设计合成了以籍次乙基为桥将雌激素通过 3 OH醚化与 4种不同哌嗪环相连的衍生物 ,包括中间体共合成了 12个化合物 ,其中 8个目标物及 3个中间体未见文献报道 .结构经质谱、核磁共振谱、红外光谱及元素分析确定 .同时测定了目标物对体外培养小鼠胚胎长骨生长的影响 ,结果显示由雌酚酮和雌二醇与不同的哌嗪环相连所得到的衍生物抑制骨吸收、促进骨形成的作用均不低于相应的母体雌激素 .表明哌嗪环的引入不影响雌激素对骨的药理作用 ,所合成的 4种化合物可以作为骨靶向雌激素的弹头 ,进一步与骨靶向载体连接 .     

Synthesis and characterization of (E)-N'-(substituted benzylidene)isonicotinohydrazide derivatives as potent antimicrobial and hydrogen peroxide scavenging agents

A series of (E)-N'-(substituted benzylidene)isonicotinohydrazide derivatives were synthesized by coupling isoniazid with differently substituted aldehydes and benzophenones in the presence of absolute ethanol along with catalytic amount of glacial acetic acid. The structure of all the synthesized compounds were confirmed and characterized by using various spectral technique like IR, 1H NMR, 13C NMR and mass spectroscopy. All the synthesized compounds were evaluated for their antimicrobial activity in terms of zone of inhibition, minimum inhibitory concentration, minimum bactericidal concentration and minimum fungicidal concentration in camparison to the standard drugs. The results revealed that all synthesized compounds had shown potent to mild biological activity. Among the synthesized derivatives, (E)-N'-(3,4-dimethoxybenzylidene)isonicotinohydrazide 2e, (E)-N'-(3,4,5-trimethoxybenzylidene)isonicotinohydrazide 2f and (E)-N'-(4-hydroxy-3-methoxybenzylidene)isonicotinohydrazide 2g were found to be the most effective antimicrobial compounds, whereas compounds 2g and 2k were the most potent antioxidants with significant hydrogen peroxide scavenging activity.     

2-（E）-亚苄基-5-芳氨基甲基环戊醇类化合物的合成及其抗炎活性研究

目的设计合成2-（E）-亚苄基-5-芳氨基甲基环戊醇类化合物，并对其抗炎活性进行初步的评价。方法以环戊酮为起始原料，通过Stork烯胺反应、Mannich缩合反应、胺交换反应和选择性还原制备目标化合物；以二甲苯致小鼠耳肿胀模型测试目标化合物的抗炎活性。结果共合成16个新化合物，其结构经^1H-NMR和MS谱确证。结论初步药理实验结果显示，4个目标化合物具有较强的抗炎活性。     

Microwave-assisted solvent-free synthesis of biologically active novel heterocycles from 3-formylchromones

A series of novel chromone derivatives have been synthesized employing 3-formylchromones and 5-acetyl-1,3-dimethylbarbituric acid as starting materials both under conventional heating method and microwave irradiation technique in good yields. The synthesized compounds were screened in vitro antibacterial activity against the representative panel of two Gram-positive bacteria and two Gram-negative bacteria. The synthesized compounds were also tested for their inhibitory action against three strains of fungus. The various compounds show potent inhibitory action against test organisms.     

Live cell imaging of bacterial cells: Pyrenoylpyrrole‐based fluorescence labeling

A novel substituted pyrenoylpyrroles was synthesized by the reaction of pyrenoyl chalcone, TosMIC and methyl iodide under mild condition. All the synthesized compounds were screened for their bioactivity, and the MIC was determined, among which few compounds showed moderate antibacterial activity toward Gram‐positive as well as Gram‐negative bacteria. Further, cytotoxicity assay ascertained that these compounds were non‐toxic to mammalian cells as well. The pyrene chromophore in the synthesized compounds ( 3a–e ) and ( 5a–e ) is responsible for the good photophysical properties which have an absorbance at λ 340 nm and emission at λ 410 nm. Hence, two of the selected novel synthesized compounds with non‐cytotoxic nature prospected for bio‐imaging of bacterial cells using high‐content screening analysis show that the molecule is suitable for microbial imaging in pathological diagnostic studies.     

Synthesis of novel norsufentanil analogs via a four‐component Ugi reaction and in vivo,docking, and QSAR studies of their analgesic activity

Novel substituted amino acid tethered norsufentanil derivatives were synthesized by the four‐component Ugi reaction. Norsufentanil was reacted with succinic anhydride to produce the corresponding carboxylic acid. The resulting carboxylic acid has undergone a multicomponent reaction with different aldehydes, amines, and isocyanides to produce a library of the desired compounds. In all cases, amide bond rotation was observed in the NMR spectra. In vivo analgesic activity of the synthesized compounds was evaluated by a tail flick test. Very encouraging results were obtained for a number of the synthesized products. Some of the synthesized compounds such as 5a , 5b , 5h , 5j , and 5r were found to be more potent than sufentanil, sufentanil citrate, and norsufentanil. Binding modes between the compounds and mu and delta‐opioid receptors were studied by molecular docking method. The relationship between the molecular structural features and the analgesic activity was investigated by a quantitative structure–activity relationship model. The results of the molecular modeling studies and the in vivo analgesic activity suggested that the majority of the synthesized compounds were more potent than sufentanil and norsufentanil.     

Anti-inflammatory, analgesic, anticonvulsant and antiparkinsonian activities of some pyridine derivatives using 2,6-disubstituted isonicotinic acid hydrazides

A series of novel thiazolo derivatives 2-15 was synthesized by initial condensation of 2,6-dihydroxyisonicotinohydrazide 1 and 2-chloro-6-hydrazinylisonicotinohydrazide 11 with different organic reagents. The pharmacological screening showed that many of these obtained compounds have good anti-inflammatory, analgesic, anticonvulsant, and antiparkinsonian activities comparable to diclofenac potassium, Voltarene(?), Carbamazepine(?), and Benzotropene(?) as reference drugs. Initially the acute toxicity of the compounds was assayed via the determination of their LD??. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, LD?? and pharmacological activities of the synthesized compounds were reported.     

苄叉基琥珀酸类衍生物的合成及降糖活性

目的设计合成结构更为简单的餐时血糖调节剂。方法以丁二酸二乙酯与苯甲醛或对氟苯甲醛为起始原料，经缩合、水解、脱水得到酸酐，再分别与不同的芳香胺、脂肪胺及氮杂环进行酰胺化，共合成了18个衍生物。利用核磁共振谱、质谱和红外光谱进行结构确认。结果小鼠体内实验表明：剂量为3.0 mg·kg^-1时，18个衍生物中17个表现出不同程度的降糖活性，其中9个具有较好的降糖活性，6个具有餐时血糖调节剂的特点。结论部分化合物具有较好的降糖活性，待进一步研究。     

阿魏酰胍丁胺类似物的设计、合成及Na~+/H~+交换器-1抑制活性

为了寻找新结构类型的Na+/H+交换器-1(NHE-1)抑制剂,以阿魏酸、胍丁胺为先导化合物,设计并合成了9个阿魏酰胍丁胺类似物。其结构经1H NMR、13C NMR和MS确证,其中化合物5f～5i为新化合物。初步的药理实验结果表明,部分目标化合物显示出较好的NHE抑制活性,其中化合物5a、5b和6c对NHE-1的抑制活性明显优于阳性对照药卡立泊来德(cariporide)。     

知母菝葜皂苷元3-位糖基化衍生物的合成

目的 为寻找活性更好的抗老年痴呆的知母螺旋甾烷型皂苷，设计并合成了一系列知，警奠皂苷元3-位糖基化衍生物。方法 使知母中提取的菝莫皂苷元3位羟基与活化的保护单糖反应，再脱去单糖保护得到目标化合物，用核磁共振氢谱、质谱和元素分析确证其结构。结果与结论 所合成的7个(A6～G6)知母螺旋甾烷型皂苷衍生物中，除半乳糖基知母螺旋甾烷型皂苷衍生物外。     

2-(E)-亚苄基-5-氨甲基环戊醇类化合物的合成及抗炎活性研究

目的设计合成2-(E)-亚苄基-5-氨甲基环戊醇类化合物,并对其抗炎活性进行初步的评价。方法以环戊酮为起始原料,通过Stork烯胺反应、Mannich反应、选择性还原制备目标化合物;以二甲苯致小鼠耳肿胀模型测试目标化合物的抗炎活性。结果共合成了12个新化合物,经1H-NMR、MS和IR确证结构。初步药理实验结果显示10个目标化合物具有较强的抗炎活性。结论目标化合物稳定性有所提高并且保留了抗炎活性。