3-甲基-7-氧-9-氟-10-烃氧基(或芳氧基)-2,3-二氢-7H-吡啶[ 1,2,3-de]苯并恶嗪-6-羧酸及其类似物(英) 的合成和抗菌以及抗肿瘤活性

合成了3－甲基－7－氧－9－氟－10－烃氧基（或芳氧基）－2,3－二氢－7H－吡啶［1,2,3－de］苯并恶嗪－6－羧酸及其类似物,体外抗菌筛选证明10－烃氧基化合物（尤其是氟乙氧基化合物3d）的抗菌作用明显优于10－羟基化合物3a。体外抗肿瘤试验证明有的化合物对LAX和P388细胞株培养具有中等或较低的细胞毒。     

2—取代—6—氧代—8—氟—9—含氮杂环—6H—咪唑并（4，5，1—ij）喹啉—5—羟酸及其类似物的合成和抗菌活性

6－氟－7（4－甲基－1－哌嗪基）－8－氨基－4－氧代－1，4－二氢喹啉－3－羧酸乙酯（5A）和脂肪酸在PPA中缩合，得2－烃基－6－氧代－8－氟－9－（4－甲基－1－哌嗪基）－6H－咪唑并（4，5，1－ij）喹啉－5－羟酸（2Ab-2Ae），6－氟－7－含氮杂环－8－氨基－4－氧代－1，4－二氢－3－喹啉羧酸（9A-9D)与各种酸在PPA中缩合或与原甲酸三乙酯缩合或经重氮化反应，可分别得到其它目的物2Af-2Ah,2Bc,2Cc,2Aa-2Da,2Bi和2Ci。体外抗菌筛选证明仅化合物2Ab和2Ac具有中等程度的抗菌作用。     

7—（3—羟基—1，5—二氮杂环庚烷—1—胺基）—1—环丙基—6—氟—1，4—二氢—4氧代喹啉—3—羧酸及其类似物的合成与抗菌活性

设计并合成了新化合物7－（3－羟基－1,5－二氮杂环庚烷－1－胺基）－1－环丙基－6－氟－1,4－二氢－4氧代喹啉－3－羧酸（5a)及其类似物5b-5d,采用标准二倍稀释法测定了其对26株有代表性的革兰氏阳性及革兰氏阴性菌的体外抗菌活性。结果表明化合物5a-5d对所测菌株的抑菌活性低于司帕沙星,而5a和5e则对革兰氏阳性菌金葡球菌有较高的活性,其最低抑菌浓度MIC值为0．125mg/L。     

7-(吡啶-N-氧-2-巯基)-1-(2-氟乙基)-6,8-二氟-1,4-二氢-4-氧喹啉-3-羧酸的合成及抗菌活性

目的：根据喹诺酮类抗菌药和抗菌防腐剂２ － 巯基吡啶－ Ｎ－ 氧化物的抗菌作用原理设计、合成化合物７ － （ 吡啶－ Ｎ－ 氧－ ２ － 巯基） － １ － （２ － 氟乙基） － ６ ,８ － 二氟－ １ ,４ － 二氢－ ４ － 氧喹啉－ ３ － 羧酸,对其抗菌活性进行了研究。方法：合成此化合物,并研究其体外抗菌活性。结果：该化合物的体外抗菌活性优于国外近期上市的喹诺酮类抗菌药———氟罗沙星。结论：此类化合物有进一步研究的价值,为进一步研究喹诺酮类抗菌药提供了一个方向。     

7-[(1 S,4S )-3,3-二甲基-2-氧杂-5-氮杂二环[2.2.1]庚烷-5-基]-喹诺酮化合物的合成与抗菌作用

以（4R）－羟基－L脯氨酸为起始原料，经8步反应合成了[(1S,4S)-3，3－二甲基－2－氧杂－5－氮杂二环[2.2.1]庚烷，以此化合物作为喹诺酮类的7－位侧链，合成了3个衍生物，并测定了它们对10株革兰阳性菌和6株革兰阴性菌的MIC值。结果表明，它们的体外抗菌活性均低于对照药加替沙星和环丙沙星。     

（E）—3—甲氧基—4—肉桂酰氧基苯乙烯侧链衍生物的合成及其药理活性

基于环氧酶-2（COX-2）/5-脂氧酶（5-LOX）双重抑制剂的设计思想,设计合成了16个（E）-3-甲氧基-4-肉桂酰氧基苯乙烯侧链衍生物,其中13个化合物未见文献报道。所有目标物的化学结构经元素分析和波谱确证。体内初步药理试验结果表明,部分化合物对二甲苯小鼠诱发耳廓肿胀模型和角叉菜胶诱发大鼠足跖肿胀模型呈现显著抑制作用。     

1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-(N-甲基-N-取代苄基氨基)-2-丙醇的合成及抗真菌活性研究

根据三唑类抗真菌药物作用靶酶－羊毛甾醇14α－去甲基化酶的三维晶体结构和药物与酶活性的位点的对接结果，设计合成了11个1－（1H－1，2，4－三唑－1－基）－2（2，4－二氟苯基）－3－（N－甲基－N－取代苄基氨基）－2－丙醇化合物，11个目标化合物均系首次报道，体外抗真菌活性试验结果表明，所有目标化合物对七种致病真菌都有不同程度的抗真菌活性，而且都比氟康唑的体外抗真菌活性好，化合物11的抗菌谱最广，抗真菌活性最高，对新型隐球菌，白色念珠菌，羊毛状小孢子菌和红色毛癣菌的抗菌活性比酮康唑高，有进一步开发的价值。化合物3，4，10也表现出较高的抗真菌活性。     

7-(吡啶-N-氧-2-巯基)-1-(2-氟乙基)-6,8-二氟-1,4-二氢-4-氧喹啉-3-羧酸的合成及抗菌活性

目的;根据喹诺酮类抗菌药和抗菌防腐剂２－巯基吡啶－Ｎ－氧化物的抗菌作用原理设计,合成化合物７－（吡啶－Ｎ－氧－２－巯基）－１－（２－氟乙基）－６,８－二氟－１,４－二氢－４－氧喹啉－３－羧酸,对其抗菌活性进行了研究。方法;合成此化合物,并研究其体外抗菌活性。     

7-[(2S)-2-羟甲基-4-氨基-1-吡咯烷基]氟喹诺酮类化合物的合成及体外抗菌活性

用反式-L-羟脯氨酸经对甲苯磺酰氯保护、甲酯化、氧化、肟化、四氢铝锂还原、叔丁氧基羰基保护后脱除对甲苯磺酰保护基,与不同的氟喹诺酮中间体缩合,最后经脱除叔丁氧基羰基等反应得到目标物,结构经1HNMR和FAB-MS确证,并进行了体外抗菌活性试验.结果表明,除化合物13对供试的大部分菌株,特别是对链球菌的体外活性相当于或优于对照药加替沙星和环丙沙星外,其余3个目标物总体活性均低于对照品.     

3—取代—4—氧—3H—咪唑并[5,1—d][1,2,3,5]四嗪—8—羧酸衍生物的合成及其抗癌活性研究

根据咪唑四嗪酮类抗癌药物构效关系研究结果,以替莫唑胺和米托唑胺为先导化合物,设计合成了10个3－取代－4－氧－3H－咪唑并[5,1-d][1,2,3,5]四嗪－8－羧酸及其衍生物,以4－氨基咪唑－5－甲酰胺盐酸盐为起始原料,经酰化,重氮化环合得到咪唑四嗪酮环,再经3位和8位官能团转化,得到目标化合物,其中5个目标化合物未见文献报道,其结构均经红外光谱,核磁共振氢谱和元素分析等数据证实,经体外抗癌活性筛选,3个化合物表现出良好的抗癌活性。     

7-[3-Hydroxy-2-halogenpropyl]-tetrahydropurine

7-[3-Hydroxy-2-halogenopropyl]-tetrahydropurines The addition of HOBr or HOJ to the allylic group (at N-7) of purine derivatives affords primary alcohols. The structure of the side chain is studied by ¹H–NMR-spectra.     

呋苄头孢菌素和呋苄青霉素钾的极谱行为研究

本文研究呋苄头孢菌素和呋苄青霉素钾的极谱行为。两样品在-1.1 V附近有一清晰的单扫描极谱波,在一定的浓度范围内蜂电流与样品浓度之间呈良好的线性关系,可用作定量分析。本文还对电极反应机理进行了初步的探讨,并证明此波具有吸附性质。     

Synthesis and antiulcer activity of (E)-5-[2-(3-pyridyl)ethenyl]-1H,7H-pyrazolo [1,5-a]pyrimidine-7-ones

A series of (E)-5-[2-(3-pyridyl)ethenyl]-1H,7H-pyrazolo-[1,5-a]pyrimidine-7-ones were synthesized and evaluated for the inhibition of stress-induced gastric ulcers in the rat after oral administration. Several molecules were found to be very active. The particularly interesting compound (E)-1-(3-chlorophenyl)-5-[2-(3-pyridyl)ethenyl]-1H,7H-pyrazolo[1,5-a]- pyrimidine-7-one was chosen for wider pharmacological investigation.     

Progress in 7-deazapurine - pyrrolo[2,3-d]pyrimidine - ribonucleoside synthesis

This review reports on the synthesis of 7-deazapurine ribonucleosides, including C-nucleosides, 2'-C-methyl derivatives and L-enantiomers. It covers the various aspects of convergent nucleoside synthesis such as the Schiff base procedure, the fusion reaction, the metal salt procedures, the Silyl-Hilbert-Johnson reaction, and the nucleobase anion glycosylation. The review discusses the scope and limitations of glycosylation reactions performed on 7-deazapurines. Peracylated ribose derivatives were now employed in the glycosylation, which overcome difficulties reported earlier.     

(+/-)-2-Amino-3,4-dihydro-7-[2,3-dihydroxy-4-(hydroxymethyl)-1- cyclopentyl]-7H-pyrrolo[2,3-d]pyrimidin-4-ones: new carbocyclic analogues of 7-deazaguanosine with antiviral activity

5-Allyl-2-amino-4,6-dihydroxypyrimidine (3) was chlorinated and ozonized to yield (2-amino-4,6-dichloro-pyrimidin-5-yl)acetaldehyde (5). Acetalization of 5 with ethanol afforded a new pyrimidine intermediate 6 which can lead to 2-amino-3,4-dihydro-7-alkyl-7H-pyrrolo[2,3-d]pyrimidin-4-ones and therefore to carbocyclic analogues of 7-deazaguanosine. The 7-substituent was a cyclopentyl analogue of the arabinofuranosyl moiety in 10a, lyxofuranosyl moiety in 10b, and ribofuranosyl moiety in 10c. Compounds 10a and 10b exhibited selective inhibitory activities against the multiplication of HSV1 and HSV2 in cell culture. Repeated administration of compound 10a at 10mg/kg ip to mice infected with HSV2 increased the number of survivors and lengthened significantly the mean survival time.     

2,6-Dithia-1,3,5-7-tetraazabicyclo[3.3.1]nonan-2,2,6,6-tetroxide

2,6-Dithia-1,3,5-7-tetraazabicyclo[3.3.1]nonan-2,2,6,6-tetroxides The sulfamides 2 react with paraformaldehyde in TFA via 3 and 4 to give the title compounds 5 . The product of the reaction from 2 with formaldehyde in water is not 1 , as suggested before, but 4 .     

Synthesis of 7-[p-(methylthio)benzoyl]-5-benzofuranacetic acid

A new method was described for the preparation of 7-[p-(methylthio)benzoyl]-5-benzofuranacetic acid6, which is an analgesic agent. Methyl 5-(2,3-di-hydrobenzofuran)acetate3 was obtained by Friedel-Crafts reaction of 2,3-dihydrobenzofuran with methyl α-chloro-α-(methylthio)actate1 and desulfurization of2. Tifurac6 was synthesized from acylation of 3 with p-(methylthio)benzoyl chloride followed by bromination of4, dehydrohalogenation, and hydrolysis of5.     

Synthesis and cytotoxic activity of 7-oxo-7H-dibenz[f,ij]isoquinoline and 7-oxo-7H-benzo[e]perimidine derivatives

A series of 7-oxo-7H-dibenz[f,ij]isoquinoline and 7-oxo-7H-benzo[e]perimidines bearing cationic side chains were prepared from aminoanthraquinones. The perimidines were prepared from 1-aminoanthraquinone by initial condensation with urea or dimethylacetamide. A series of 2-, 4-, 8-, and 11-carboxy derivatives of the dibenzisoquinolines were prepared from aminoanthraquinonecarboxylic acids. The cationic derivatives were prepared from these via amide, amine, or methylene linkers to study the effects of side chain positioning on biological activity. Within the series of carboxamide-linked compounds, the order of increasing cytotoxicity was 8- < 4- < 2- < 11-. The 2- and 4-carboxamides showed substantial growth delays against in vivo subcutaneous colon 38 tumors in mice, but the 11-carboxamide had curative activity in this refractory model and is being investigated further.