苯并咪唑类化合物的合成及辐射增敏作用

为了寻找低毒和有效的辐射增敏剂,合成了苯并咪唑类化合物2-硝基苯并咪唑-1-甲酸乙酯,2-羟基苯并咪唑-1-甲酸乙酯及1-取代2-(3’-吡啶基)-5(6)-硝基苯并咪唑类化合物,并对小鼠Ehrlich腹水癌细胞进行了辐射增敏实验,初步结果证明所试化合物有不同程度的辐射增敏效果。     

有效的放射增敏剂:二硝基咪唑衍生物的合成及其生物活性

对多种芳香硝基化合物的放射增敏作用研究发现,1-(2-羟基-3-甲氧丙基)-2-硝基味唑(Misonidazole)是一有效的放射增敏剂,但因其神经毒性和诱变性,妨碍其临床应用。为寻找低毒和有效的放射增敏剂,考虑到分子的亲电性的重要作用以及芳环上引入吸电子基可增大活性,合成了一系列2,4-二硝基咪唑衍生物(2～4),并采用中国仓鼠低氧细胞(V-79),进行放射增敏体外试验。     

3-硝基-1,2,4-三唑类乏氧细胞放射增敏剂的构效关系

为了寻找毒性低、增敏作用强的乏氧细胞放射增敏剂,设计并合成了一系列5-溴-,5-甲基-,和5-未取代的3-硝基-1,2,4-三唑-1-乙酰胺类化合物,用HeLaS3细胞进行了体外试验。结果表明5-溴取代衍生物的增敏作用强于相应的5-甲基-或5-未取代的硝基三唑衍生物,但是它们的毒性亦增大。修饰1位乙酰胺侧链也可以改变化合物的增敏作用和亲脂性。在所测定的化合物中TA-101[2-(3-硝基-1-三唑基)乙酰胺]由于有高的增敏作用和低亲脂性,可能是一个有希望的放射增敏剂。     

3－硝基－1，2，4－三唑类乏氧细胞放射增敏剂的构效关系

为了寻找毒性低、增敏作用强的乏氧细胞放射增敏剂，设计并合成了一系列５－溴－，５－甲基－，和５－未取代的３－硝基－１，２，４－三唑－１－乙酰胺类化合物，用ＨｅＬａＳ３细胞进行了体外试验。结果表明５－溴取代衍生物的增敏作用强于相应的５－甲基－或５－未取代的硝基三唑衍生物，但是它们的毒性亦增大。修饰１位乙酰胺侧链也可以改变化合物的增敏作用和亲脂性。在所测定的化合物中ＴＡ－１０１［２－（３－硝基－１－三唑基）乙酰胺］由于有高的增敏作用和低亲脂性，可能是一个有希望的放射增敏剂。     

若干带有氮杂环取代的氨基酸及其酰肼的合成

氮八环、氮七环、氮六环与甲醛及甲酰氨基丙二酸二乙酯缩合,生成相应的α-(N-氮杂环甲基)甲酰氨基丙二酸二乙酯(Ⅳ),再用盐酸水解后得α-氨基-β-(N-氮杂环基)丙酸(Ⅲ).氮八环、氮七环、氮六环与氯乙酸乙酯及α-氯丙酸乙酯缩合,生成相应的α-(N-氮杂环基)丙酸乙酯及乙酸乙酯(Ⅴ),然后用盐酸水解,制得α-(N-氮杂环基)取代的丙酸及乙酸(Ⅱ)的盐酸盐.V分别和水合肼、苯甲肼或苯乙肼在封管中加热缩合,制成相应的酰肼(Ⅵ).其中某些化合物具有降压及冠脉扩张作用.     

卟啉硝基咪唑类衍生物的合成及放射增敏作用

目的设计合成卟啉硝基咪唑类化合物,评价其体外肿瘤放射增敏活性,寻找新的肿瘤放射增敏剂。方法以吡咯、苯甲醛、硝基咪唑为原料,经环合、溴代、取代、络合等反应合成卟啉硝基咪唑类化合物及其金属配合物。采用MTT法考查该系列衍生物对人宫颈癌Helo细胞株的放射增敏活性。结果合成了12个未见文献报道的新化合物,其结构经紫外光谱、ESI质谱、红外光谱和核磁共振氢谱确证。在4Gy照射剂量下,化合物15、16、18、19对人宫颈癌Helo细胞株显示出很好的放射增敏活性,对肿瘤细胞的抑制率达到95%左右。结论金属卟啉结构单元的引入,极大地提高了硝基咪唑类的放射增敏活性。     

新型头孢菌素的合成和抑菌试验

从7-氨基头孢烷酸(7 ACA)和7-氨基-3-去乙酰氧基头孢烷酸(7 ADCA)合成了六个7-取代连氮基头孢菌素和六个7α-甲氧基-7β-取代腙基头孢菌素,体外抑菌试验表明大部分化合物的抑菌活性较弱。     

PPARγ激动剂的设计、合成及其胰岛素增敏活性

目的寻找新的高效、低毒的PPARγ激动剂。方法以JTT-501和JTT-20993为先导化合物，设计并合成新的丙二酸类和异恶唑类化合物，并测定其胰岛素增敏活性。结果共合成了8个新化合物,用核磁共振、质谱和红外光谱进行结构确证，并用胰岛素筛选模型初步评价了这些化合物的胰岛素增敏活性。化合物1A-4A显示胰岛素增敏活性,其中化合物1A和3A有较强活性。结论化合物1A和3A值得进一步评价。     

锗丙酰氨基酸酯倍半氧化物的合成

通过锗丙酰氯与氨基酸酯的酰氨化反应、继而水解，合成了三个新的锗丙酰氨基酸酯倍半氧化物和一个部分水解产物。用元素分析，IR、NMR FAB－MS等确定了其组成和结构，同时还应用NMR屏蔽效应新原理阐明了其^1H，^13CNMR反常取代基效应。     

硝基(芳亚胺基)二乙基硫代硫酸钠和硝基苯丙氮酸衍生物的合成和放射增敏作用

乏氧细胞对射线所具有的较大抗性是对某些人类肿瘤进行放疗失效的主要原因。放射增敏剂的研究目的是为了提高射线在正常组织可耐受剂量下对肿瘤细胞的杀伤率,从而提高放疗效果。目前试用于临床的放射增散剂misoniizole(MISO)是一种硝基咪唑类化合物,由于其较强的神经毒性,限制了这种药物的推广和使用。为寻找新的低毒有效的放射增敏剂,我们设计并合成了一系列化合物,试验了它们对离体Hela-S_3细胞的放射增敏作用。     

Synthesis and antimycobacterial activity of novel 4-[5-(substituted phenyl)-1-phenyl-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-3-pyrazolyl]-2-methylphenol derivatives

In the present investigation, 4-hydroxy-3-methylacetophenone, on condensation with appropriate aldehydes in methanolic potassium hydroxide solution, yielded the corresponding chalcones (C_I-XI). These corresponding chalcones were reacted with phenyl hydrazide in glacial acetic acid, which led to the formation of novel 4-[5-(substituted phenyl)-1-phenyl-4,5-dihydro-1H-3-pyrazolyl]-2-methylphenol derivatives. All newly synthesized compounds were evaluated for their antimycobacterial activities against isoniazid-resistant Mycobacterium tuberculosis using agar dilution. 4-[5-(4-Fluoro phenyl)-1-phenyl-4,5-dihydro-1H-3-pyrazolyl]-2-methylphenol showed good antimycobacterial activity, with a minimum inhibitory concentration of 0.62 μg/ml.     

Synthesis and Evaluation of Novel 2‐Substituted‐quinazolin‐4(3H)‐ones as Potent Analgesic and Anti‐inflammatory Agents

A novel series of 2‐substituted‐quinazolin‐4(3H)‐ones were synthesized by reacting 3,5‐disubstituted‐anthranilic acid with acetic anhydride/benzoyl chloride, which were further reacted with different primary amines to obtain 2,6,8‐substituted‐quinazolin‐4(3H)‐ones 6a–f , 7 , 8 . All the synthesized compounds were characterized and screened for analgesic and anti‐inflammatory activities. Compounds 6,8‐dibromo‐2‐phenyl‐3‐(4′‐carboxyl phenyl)quinazolin‐4(3H)‐one 7 and 6,8‐dibromo‐2‐phenyl‐3‐(2′‐phenylethanoic acid)quinazolin‐4(3H)‐one 8 displayed good analgesic and anti‐inflammatory activity in comparison to the reference standards acetyl salicylic acid and indomethacin, respectively.     

Synthesis and Molluscicidal Activity of New Derivatives of 1-(Hydroxy/substituted Phenyl)-3-arylpropenones

Several 1-(hydroxy/substituted phenyl)propenones were tested as molluscicidal agents among which the 1-(2-hydroxy/substituted phenyl)-3-(2-furyl)propenones 1a - c show the most promising results. In an attempt to improve their activity, new dihydropyrazolo[1,5-c][1,3]benzoxazines, their thio and their dehydrogenated derivatives were prepared. The pyrazolo[1,5-c][1,3]benzoxazines 4a , b were hydrolyzed affording the 3-(2-furyl)-5-(2-hydroxy/substituted phenyl) pyrazoles 8a , b . The hydroxyimino derivatives 10a - c were synthesized together with their corresponding isoxazole derivatives 11a - c . - Molluscicidal assay indicated that the oximes 10b , c . the isoxazole 11b , the pyrazole 8b , and its N-carbamoyl derivative 9b are most effective. They have in common the conjugated system shown in Fig. 1 which is presumably the active core.     

2-芳基-3-吲哚取代乙酰胺类衍生物的合成及抗焦虑活性

目的　合成2-芳基-3-吲哚取代乙酰胺类化合物,从中筛选有抗焦虑作用而无镇静、肌松等副作用的活性化合物。方法　由取代苯和琥珀酸酐经傅-克反应得到取代苯甲酰基丙酸,取代苯甲酰基丙酸和氯甲酸乙脂生成混合酸酐,再和相应的胺反应得到取代酰胺,取代酰胺和取代苯肼经费歇尔反应得到目标化合物。结果　得到新化合物20个。结论　初步受体结果表明,多数化合物均与外周苯二氮受体有较强结合,在小鼠高架十字迷宫试验中发现一些化合物有明显的抗焦虑作用,且不能拮抗印防己毒素(PTX)诱发的惊厥作用,显示无镇静作用     

Novel Steroidal 1,4-Diketones and Pyridazine Derivatives as Potential Antiestrogens

A series of steroidal 1,4-diketone derivatives was synthesized by acid-catalyzed condensation of 2-acetylestradiol-17β-acetate with substituted phenylglyoxals. Conversion of the products into the corresponding pyridazine derivatives was achieved by reaction with hydrazine hydrate. The synthesized compounds were evaluated for their uterotrophic, antiuterotrophic, and antifertility activities in mature female albino rats. Among the compounds tested, the phenyl 2 , p-bromophenyl 3 , and p-methoxyphenyl 5 diketone derivatives displayed uterotrophic activity of 72%, 72%, and 91%, respectively. The gradation of antiestrogenic activity was assessed in vivo by the inhibition of the estrone-stimulated uterine growth. Compounds 2–5 showed moderate antiestrogenic activity of 53–56%. None of the tested compounds elicited antifertility activity as assessed by the post-coital antiimplantation activity test.     

二氢叶酸还原酶抑制剂:5-取代苯硫基(硒基)-2,4-二氨基嘧啶类化合物的合成和抑酶活性

According to the principle of isosterism the-CH₂-group of 5-(substituted benzyl)-2, 4-diaminopyrimidine was modified by—S—and—Se—and some 5-(substituted phenyl)thio-2, 4-diaminopyrimidines and 5-(substituted phenyl)seleno-2,4-diaminopyrimidines were synthesized. Their inhibitory activities on L. casei and chicken liver dihydrofolate reductase were determined. Preliminary data showed that the inhibitory activities of these compounds were less than those of the corresponding 5-(substituted benzyl)-2, 4-diaminopyrimidines. Their selectivities are also decreased.     

Scalable synthesis and antibacterial evaluation of 2‐(3‐(N‐(substituted phenyl)sulfamoyl)ureido)benzothiazoles

A new series of 2‐(3‐(N‐(substituted phenyl)sulfamoyl)ureido)benzothiazoles was synthesized via a one‐pot efficient and scalable method, involving the condensation of 2‐aminobenzothiazoles derivatives, substituted anilines, and chlorosulfonyl isocyanate. The products were obtained in good yield with a simple workup, and their structures were confirmed from their spectral analyses. The synthesized compounds were further screened for their antibacterial activity against Gram‐positive and Gram‐negative pathogenic strains. The molecules show promising activity in the MIC value range of 2–0.25 µg/ml against selected bacterial strains, especially against nonfermentative carbapenem‐resistant bacteria (Pseudo VIM‐2 and Acinetobacter baumanni).     

2-甲基-5,6-次甲二氧-3-吲(口朶)丙胺衍生物的合成

本文报道以胡椒醛为原料,通过2-甲基-5,6-次甲二氧-3-吲哚丙酸,合成了8个2-甲基-5,6-次甲二氧-3-吲哚丙胺衍生物,药理初步试验,发现化合物(Ⅳ)具有显著增强环已烯巴比妥的作用,且毒性较小。     

Synthesis of Novel 2,5‐Disubstituted 1,3,4‐Thiadiazoles for Their Potential Anticonvulsant Activity: Pharmacophoric Model Studies

A series of novel N¹‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N⁴‐(4‐substituted benzaldehyde)‐semicarbazone 1 – 12 , N¹‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N⁴‐[1‐(4‐substituted phenyl)ethanone]‐semicarbazone 13 ‐ 16 , and N¹‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N⁴‐[1‐(4‐substituted phenyl) (phenyl) methanone]‐semicarbazone 17 – 20 were synthesized for their anticonvulsant activity. The chemical structures of the compounds were proved by elemental and spectral (IR, ¹H‐NMR, ¹³C‐NMR, and MS) analysis. The anticonvulsant potential of the compounds was investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetrtrazole (scPTZ) models. Compound 19 was found to possess significant anticonvulsant activity in both the models employed for anticonvulsant evaluation. Compounds 8 , 13 , 15 , and 16 also demonstrated a marked anticonvulsant property. The results of the present study validated that the pharmacophore model with four binding sites is essential for anticonvulsant activity. The efforts were also made to establish structure‐activity relationships among the synthesized compounds.