磺胺的噻二嗪硫酮衍生物的合成及抑菌活性研究

利用药物化学骈合理原理设计并合成了一系列新的３，５－二取代１，３，５－噻二嗪－２－硫酮类化合物，基结构被红外光谱与紫外光谱及元素分析所证实，抑菌活性试验显示良好的抑菌活性。     

噻二嗪硫酮衍生物的合成及抑菌活性研究

合成了４种新的３－苯基－５－取代的－四氢－２Ｈ－１，３，５－二噻一嗪－２－硫酮类化合物，其结构被红外光怀紫外光谱及元素分析所证实，并进行了初步抑菌活性试验。     

5—（β—萘氧甲基）—1,3,4恶二咪—2—硫酮和两种曼尼希碱的合成及抑菌 …

用β－萘酚为原料经酯化，肼解、环化合成了５－（β－萘氧甲基）－１，３，４－恶二咪－２－硫酮。然后经曼尼希碱反应，生成两种曼尼希碱。其化学结构经红外光谱，核磁共振和元素分析证实。并进行了初步的抑菌活性实验。     

羟基胆烷酸类衍生物的抗癌活性研究

报道３β，５α，６β－三羟基胆烷－２４－酸及其生物的合成及对小鼠Ｌ１２１０白血病细胞的体外抗癌活性，实验表明，３β，５α，６β－三羟基胆烷－２４－酸，３β，５α，６β－三羟基胆烷－２４－酸甲酯及３β，６β－二乙酰氧基－５α－羟工胆烷－２４－酸甲酯有较好的抗癌活性。     

3—异丙基,3—正戊基环戊二酮—1,2Mannich碱衍生物的合成及抗？…

以３－异丙基、３－正戊基环戊二酮－１，２为母体化合物，设计合成了９个未见文献报道的Ｍａｎｎｉｃｈ碱衍生物，并在体外进行了抗癌活性评价。初步药理活性筛选结果表明，３－正戊基环戊二酮－１，２Ｍａｎｎｉｃｈ碱衍生物的抗癌活性较强，３－异丙基环戊二酮－１，２Ｍａｎｎｉｃｈ碱衍生物的活性相对较弱，我数化合物的抗癌活性优于阳性对照药５－Ｆｕ。     

氧代固醇类化合物的抗癌活性研究4──胆甾烷－3β，5α，6β（6α）－三醇和胆甾－4－烯－3β，6β（6α）－二醇的琥珀酸单酯钠合成与抗癌活性

本文报道了胆甾烷－３β，５α，６β－三醇、胆甾烷－３β，５α，６α－三醇、胆甾－４－烯－３β，６β－二醇、胆甾－４－烯－３β，６α－二醇及其琥珀酸单酯和它们的钠盐的合成，体外试验的初步结果表明：胆甾烷－３β，５α，６β－三醇－３－琥珀酸单酯钠（１７），胆甾烷－３β，５α，６α－三醇－３，６－双琥珀酸单酯钠（１８），胆甾－４－烯－３β，６β－二醇－３，６－双琥珀酸单酯钠（１９）及胆甾－４－烯－３β，６α－二醇－３，６双琥珀酸单酯钠（２０）具有较明显的抗癌活性。     

5α-胆甾烷-3β，7-二醇水溶性衍生物的合成及体外抗癌活性

为考察胆甾－５－烯－３β,７β－二醇双琥珀酸单酯钠结构中的５,６－双键是否为其产生抗癌活性的必要部位,合成了５α－胆甾烷－３β,７－二醇３－琥珀酸单酯及其水溶性和衍生物－乙醇胺盐,哌嗪盐及Ｎ－２乙基哌嗪盐,体外抗癌活性试验表明,所合成的化合物具有一定程度的抗癌活性。     

单胺菌素─喹诺酮酰胺衍生物的合成

为探索喹诺酮类化合物充当单胺菌素３位边链酸的构效关系，合成了４个未见文献报道的单胺菌素－喹诺酮酰胺衍生物（５ａ）～（５ｄ）．它们是以氧氟沙星（８）、氟罗沙星（９）或诺氟沙星前体（１－乙基－６－氟－７－氯－１，４－二氢－４－氧代喹啉－３－羧酸）（１０）通过ＤＣＣ－ＨＯＢＴ法酰化卡芦莫南母核（６）或氨曲南母核（７）得到的．初步体外抑菌试验表明：（５ａ）～（５ｄ）的最低抑菌浓度（ＭＩＣ）均大于１００ｍｇ／Ｌ     

5—氟尿嘧啶衍生物的合成及其抗肿瘤活性

以相转移催化法。使２－Ｏ－丁基（或苄基）－５－氟－３Ｈ－４嘧啶酮与含卤素化合物作用，合成了１１个２，３－二取代５－－氟－４嘧啶酮类化合物，２－Ｏ－苄基－３－Ｎ－取代－５－氟－４－嘧啶酮在Ｐｄ－Ｃ催化剂存在与氢解，制备了５个３－Ｎ－取代－５－氟－２，４－嘧啶二酮化合物，这１６个化合物均未见文献报道。其结构经ＩＲ，Ｈ－ＮＭＲ和ＭＳ所证实，其中有些化合物具有一定的抗肿瘤活性。     

1—环丙基—5—取代—7—（4—甲基哌嗪基）—6,8—一二氟—1,4—二氢…

利用３Ｄ－ＱＳＡＲ中的ＣｏＭＦＡ方法研究了１－环丙基－５－取代－７－（４－甲基哌嗪基）－６，８－二氟－１，４－二氢－４－氧－３－喹啉羧酸定量构效关系。研究表明，从ＰＬＳ分析的ｒｅｖ，ｒ值看，模型有较强的预测能力；从立体与静电作用分数比可看出，５位取代基对活性的影响立体效应起主要作用，但静电效应亦十分重要，依据ＣｏＭＦＡ系数图设计了一些新化合物，预测结果表明，以５位氨基对抑制革兰氏阳性、阴性菌的活性     

磺胺的噻二嗪硫酮衍生物的合成及抑菌活性研究

利用药物化学骈合原理设计并合成了一系列新的3，5-二取代1，3，5-噻二嗪-2-硫酮类化合物，其结构被红外光谱与紫外光谱及元素分析所证实，抑菌活性试验显示了良好的抑菌活性．     

2, 3-Bis(5-alkyl-2-thiono-1, 3, 5-thiadiazin-3-yl) propionic acid: one-pot domino synthesis and antimicrobial activity

In a search for promising antibacterial and antifungal compounds, two new series of 2, 3-bis(5-alkyl-2-thiono-1, 3, 5-thiadiazin-3-yl)propionic acid 1 and their corresponding N, N-dimethylpropionamide 6 have been synthesized. The reaction of 2, 3-diaminopropionate 3, carbon disulfide, formaldehyde, and the appropriate alkyl amines furnished the title compound 1. N, N-dimethylpropionamides 6 were obtained by the reaction of 1 with dimethyl amine in the presence of POCl(3). The newly prepared compounds were screened in vitro against certain strains of Gram-positive and Gram-negative bacteria and compared with nalidixic acid and ciprofloxacin. Moreover, the title compounds were tested for their antifungal activity in vitro against Candida albicans, phytopathogenic, Penicillum expansum and Trichoderma hazianum, and aflatoxin-producing Aspergillus flavus. These compounds exhibit varied activity against the tested pathogenic bacteria and remarkable inhibitory effects on growth or sporulation of some of the tested fungal species.     

Synthesis and Antimicrobial Activity of Some New 2-(3-(4-Aryl)-1-phenyl-1H-pyrazol-4-yl) Chroman-4-ones

Seven new 2-(3-(4-aryl)-1-phenyl-1H-pyrazol-4-yl) chroman-4-ones (4a-4g) have been synthesized by cyclization of 2-hydroxychalcone analogues of pyrazole 3a-3g using conc. HCl in acetic acid. The structures of the compounds 4a-4g were established by the combined use of (1)HNMR, IR and mass spectra. All the seven compounds were tested in vitro for their antibacterial activity against two Gram positive bacteria namely Staphylococcus aureus and Bacillus subtilis and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The compounds 4b, 4c, 4e, 4f, 4g have displayed good antibacterial activity when compared with commercially available antibiotic, ciprofloxacin. These compounds also were screened for their antifungal activity against two ear pathogenic fungi, namely Aspergillus Niger and A. flavus. The compounds 4a, 4c, 4d, 4g exhibited good antifungal activity when compared with commercially available antifungal, fluconazole.     

Research on Antifungal and Antimycobacterial Agents. Synthesis and Activity of 4-Alkylthiopyridine-2-carbothioamides

A series of 4-alkylthiopyridine-2-carbothioamides have been prepared and evaluated in vitro for antimicrobial activity. Chemical structures have been demonstrated by IR and ¹H NMR data and by elemental analysis. The antimycobacterial activity of these compounds against Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium, and Mycobacterium fortuitum, and the antifungal activity against Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon beigelii, Trichophyton mentagrophytes, Aspergillus fumigatus, and Absidia corymbifera were determined by the MIC values. Compounds 3 exhibit good antimycobacterial activity compared to isoniazide. A moderate antifungal activity was observed against T. mentagrophytes. Activity is influenced by hydrophobicity of the alkyl group.     

S-Acyl derivatives of thiosalicylamides having antifungal activity. II]

Some S-acyl derivatives of N-alkylthiosalicylamides [Table I: substances (I leads to XXXI)] were prepared and tested for antifungal activity. The substances, most of which had not been previously reported, were prepared by condensation of 2-mercapto-N-alkylbenzamides with suitable acylating agents. The antifungal activity of the compounds was tested in vitro against Candida albicans and Trichophyton mentagrophytes. For some compounds the was tested activity against the above strains fungicidal, Candida tropicalis and Saccharomyces cerevisiae. Many of the compounds proved to have high antifungal activity comparable with that of Clotrimazol. The results extended knowledge on the structure-antifungal activity relationships of this class of compounds. The compounds with the highest antifungal activity were: 2-acetylmercapto-N,n-heptylbenzamide (XXVIII); 2-acetylmercapto-5-Cl-N,n-propylbenzamide (XIV); 2-acetylmercapto-N,n-octylbenzamide (XXXI); 2-acetylmercapto-N,n-pentylbenzamide (XXV); 2-acetylmercapto-N,n-hexylbenzamide (XXVII).     

Synthesis and biological evaluation of some pyrazolinylpyridines and pyrazolylpyridines

Various new 2-(1'-acetyl-5'-substituted-aryl-2'-pyrazolin-3'-yl)aminopyridines (3a-3e) and 2-(1'-phenyl 5'-substituted aryl-2'-pyrazol-3'-yl)aminopyridines (4a-4e) have been derived from 2-(substituted benzylidenylacetyl)aminopyridines (2a-2e). The structure of these compounds have been elucidated by elemental and spectral (IR, 1H-NMR, mass) analysis. Furthermore, above said compounds were evaluated for their insecticidal, antifungal, and antibacterial activities. Compound 4b 2-[1'-phenyl-5'-(o-chlorophenyl)-2'-pyrazol-3'-yl]aminopyridine, when compared for insecticidal and antifungal activities with parathion and fluconazole, respectively, was found to be the most potent one in this series. It also possessed remarkable antibacterial properties.     

Genomic and genetic approaches for the identification of antifungal drug targets

Understanding how novel antifungal compounds work in target cells is useful not only in facilitating the discovery of new drugs but also new tools that can be used for further exploration of the targeted biological pathways and their regulation. Various genomic and genetic technologies have been developed in the model yeast Saccharomyces cerevisiae, and have been successfully used to identify drug target pathways. This review discusses the methods developed for some of these technologies, and how they have been used to evaluate the cellular pathways affected by a variety of therapeutic drugs and inhibitors. The advantages and disadvantages of each method are considered, and new advances are highlighted where applicable. The investigation of the mechanism of action of new antifungal compounds will undoubtedly lead to the development of new antifungal therapies targeting new fungal pathways that are more specific and less toxic than currently available antifungal drugs.     

Emerging novel antifungal agents

Promising new compounds have recently been identified in an effort to supplement the relatively sparse portfolio of antifungal drugs. Many of these compounds have defined mechanisms of action against fungal cells and have, in some cases, aided the identification of new selective targets in fungi. For most of these compounds, however, factors such as a narrow spectrum of activity, susceptibility to efflux pumps, protein binding, serum inactivation and poor pharmaceutical properties prevent their use in the clinic. Even so, these compounds are novel substrates for synthetic modifications that could lead to the discovery of future antifungal drugs.     

硫色满酮3位Mannich碱衍生物的合成及其抗真菌活性

目的 设计、合成硫色满酮3位Mannich碱类化合物，并对其抗真菌活性进行初步评价。方法 以对氟苯硫酚为原料，经多步反应合成目标化合物，并测定目标化合物的抗真菌活性。结果共合成了10个未见文献报道的新化合物，经红外光谱、核磁共振氟谱及元素分析确证了其结构。其中化合物3对大部分供试真菌活性强于或相当于对照品克霉唑。结论 硫色满目3位取代Mannich碱具有较强的抗真菌活性。     

Therapeutic drug monitoring of antifungals: pharmacokinetic and pharmacodynamic considerations

Therapeutic drug monitoring of any pharmacologic agent should be considered when there is both significant pharmacokinetic variability and strong, clinically relevant, exposure-effect relationships. Many antifungal drugs exhibit marked variability in drug concentration as a result of inconsistent absorption, metabolism, elimination, or interaction with concomitant medications. For each of the available antifungal drugs, both preclinical and clinical trials have exhibited a relationship between serum concentrations and treatment efficacy. For a smaller subset of compounds, a similar relationship has been identified for the toxicity. The kinetic variability among patients falls outside the therapeutic window for a group of four antifungal compounds. This review summarizes the current literature on therapeutic drug monitoring for these antifungal agents.