利巴韦林的合成

1H-1,2,4-三唑-3-甲酰胺经六甲基二硅胺烷活化,所得1-三甲基硅烷基-1H-1,2,4-三唑-3-甲酰胺和四乙酰核糖经缩合得1-β-D-三乙酰呋喃核糖基-1,2,4-三唑-3-甲酰胺,再经甲醇的氨饱和溶液氮解,制得抗病毒药利巴韦林,总收率约为65%.     

氟康唑的合成工艺研究及优化

目的 研究高效广谱抗真菌药物氟康唑的合成路线并优化其工艺。方法 以间二氟苯为起始原料,经酰基化、烷基化、环氧化、缩合得氟康唑,并考察各步的反应原理和影响因素。结果与结论 第一步采用无溶剂法;第二步以甲苯为溶剂,最佳投料比m（酰化产物） : m（NaHCO3）: m（1H-1,2,4-三氮唑）= 1 : 2 : 1,以PEG-600为相转移催化剂,回流反应5 h;第三、四步“一锅煮”为最优工艺条件。该路线条件温和,原料廉价易得,成本低,产物纯度高,总收率（56%）远高于相关报道路线,适合工业化生产。     

新镇静安眠药物——舒坦乐安定的合成

舒坦乐安定,化学名:8-氯-6-苯基-4H-[1,2,4]-S-三氮唑[4,3-a][1,4]苯骈二氮杂(艹卓),结构式:     

来曲唑的合成

4-溴甲基苄腈与1,2,4-1H-三唑钠反应得4-[(1H-1,2,4-三唑-1-基)甲基]苄腈,然后在叔丁醇钾的作用下与4-氟苄腈反应得来曲唑,总收率为54.8%。     

新型三唑二氧戊环类化合物的合成、晶体结构及抗真菌活性

目的合成(E)1-[4-(2,4-二氟苯基)-2-[2-(4-氟苯基)-乙烯基]-[1,3]二氧戊环-4-甲基]-1H-[1,2,4]三氮唑化合物的几何异构体,测定其晶体结构,并考察其体外抗真菌活性。方法以间二氟苯为起始原料,经Friedel-Crafts反应、与三氮唑缩合、环氧化,得到中间体1-[2-(2,4-二氟苯基)-2,3-环氧丙基]-1H-1,2,4-三唑甲磺酸盐,将环氧化物甲烷磺酸盐水解,然后与对氟肉桂醛缩合脱水制得目标化合物6 Ka和6 Kb,经1H NMR、MS和X-射线单晶衍射测定结构,并测试其体外抗真菌活性。结果 6 Ka属单斜晶系,空间群P2(1)/c,为顺式构型。6Kb属单斜晶系,空间群P2(1)/n,为反式构型。目标化合物对5种致病真菌在体外均有很强的抑菌活性。化合物6 Kb的抑菌活性优于化合物6Ka。结论该类型反式构型化合物的体外抗真菌活性优于其顺式构型。     

3-取代三唑醇类化合物的合成及抗真菌活性

目的设计合成1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-烷氧基苯基哌嗪-2-丙醇和1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-取代硫醚-2-丙醇化合物,并进行体外抗真菌活性测试.方法以间二氟苯为起始原料,经多步反应,得到中间体环氧化物甲烷磺酸盐,再与各种烷氧基苯基哌嗪和取代硫醇开环得到目标化合物,按国际标准抗真菌敏感性实验方法测定其体外抗真菌活性.结果共合成12个(其中11个为新化合物)目标化合物,经元素分析,1H-NMR和IR确证结构,其中4个化合物的抗真菌活性强于对照品氟康唑和酮康唑.结论含烷氧苯基哌嗪侧链的三唑醇类化合物具有较强的抗真菌活性.     

1,2,4-三唑-3-羧酸甲酯合成中脱氨的改进

1,2,4-三唑-3-羧酸甲酯(1)是抗病毒药三氮唑核苷(ribavirin)合成的重要中间体,是从氨基胍,经草酰化、环合、酯化、重氮化脱氨制得:     

酶法生产三氮唑核苷的进展

<正>三氮唑核苷（Ribavirin）化学名为1-β-D呋喃核糖苷-1,2,4-三氮唑-3-甲酰胺（1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide）,其化学结构式为:     

新型三氮唑醇类抗真菌药物合成(Ⅰ)

在运用比较分子力场分析法(CoMFA)对122个氮唑类抗真菌化合物进行三维定量关系(3D－QSAR)研究的基础上设计合成了4个1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-(3-取代-1H-吲哚-1-基)-2-丙醇化合物和4个1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-(3-取代苯基-4(1H)-取代喹啉酮-1-基)-2-丙醇化合物。所有目标化合物均未见文献报道,结构经     

1H-1,2,4-三唑-3-甲酸甲酯的合成

1,2,4-三唑与甲醛在Ba(OH)2·8H2O作用下进行亲核加成得到3-羟甲基-1H-1,2,4-三唑,再经氧化和酯化制得1H-1,2,4-三唑-3-甲酸甲酯,总收率32%,纯度98%.     

Selective inhibition of virus multiplication by new acylated 1,2,4-triazole derivatives

Six out of 99 new acylated 1,2,4-triazole derivatives specifically inhibited rubella virus replication in RK 13 cell cultures. These are the following: 3-methylthio-5-(2-chlorobenzamido)-1H-1,2,4-triazole; 3-methylthio-5-(2-bromobenzamido)-1H-1,2,4-triazole; 3-methylthio-5-(2-methylbenzamido)-1H-1,2,4-triazole; 3-methylthio-5-(2-nitrobenzamido)-1H-1,2,4-triazole; 3-methylthio-5-(2-methylthiobenzamido)-1H-1,2,4-triazole and 3-ethylthio-5-(2-methylbenzamido)-1H-1,2,4-triazole. The compounds did not directly interfere with the infectivity of the rubella virus particles and the antiviral effect was demonstrable only within cells infected with rubella virus. The active compounds did not inhibit the replication of herpes simplex virus type 1, influenza virus and adenovirus in cell culture systems. Structure-activity relationships are discussed.     

Synthesis and anticonvulsant activity of some alkanamide derivatives

A group of N-phenylacetamide, N-phenylpropanamide and N-benzylamide derivatives bearing 5-membered heterocyclic rings such as pyrazole, 1,2,4-triazole and imidazole rings at omega position were synthesized and their anticonvulsant activity was evaluated in the maximal electroshock test. The results indicated that the 1,2,4-triazole ring leads to superior activity than the pyrazole ring and inserting a CH2 group into the anilide structure leading to N-benzyl derivatives did not change the anticonvulsant activity, but caused a noticeable decrease in duration of action. The most active compound was 2-(1H-1,2,4-triazole-1-yl)-N-(2,6-dimethylphenyl)acetamide.     

氟康唑及其类似物的合成方法改进

制备氟康唑及其类似物时,用超声波加速取代溴苯形成格氏试剂,用PEG600作相转移催化剂进行N-烷基化,使合成过程快速易行。     

Synthesis of 3-(3,4-dimethoxyphenyl)-1 H-1,2,4-triazole-5-thiol and 2-amino-5-(3,4-dimethoxyphenyl)-1,3,4-thiadiazole derivatives exhibiting anti-inflammatory activity

New 1-acylderivatives of 5-alkylthio-3-(3,4-dimethoxyphenyl)-4H-1,2,4-triazole (5c-f, 6d-f) were synthesized by the acylation of 5-alkylthio-3-(3,4-dimethoxyphenyl)-4H-1,2,4-triazoles (3, 4) with acyl chlorides. The compounds 3, 4 were obtained by the alkylation of 3-(3,4-dimethoxyphenyl)-1H-1,2,4-triazole-5-thiol (2) sodium salt with alkyl iodides. Compound 2 and 2-amino-5-(3,4-dimethoxyphenyl)-1,3,4-thiadiazole (8) were prepared by the treatment of 3,4-dimethoxybenzoylthiosemicarbazide (1) with sodium hydroxide or acetyl chloride (and then sodium hydroxide), respectively. Related 2-acylamino-5-(3,4-dimethoxyphenyl)-1,3,4-thiadiazoles (7c, e, f) were synthesized by the acylation of compound 8 with acyl chlorides. 3-(3,4-Dimethoxyphenyl)-4-phenyl-4,5-dihydro-1H-1,2,4-triazole-5-thione (9) was N-acylated with acyl chlorides or S-methylated with iodomethane to give 1-acyl-3-(3,4-dimethoxyphenyl)-4-phenyl-4,5-dihydro-1H- 1,2,4-triazole-5-thiones (10a, b) or 3-(3,4-dimethoxyphenyl)-5-methylthio-4-phenyl-4H-1,2,4-triazole (11) respectively. The synthesized compounds 6d, 7a, c, 10a, b, 11 exhibit anti-inflammatory activity.     

Synthesis and biological evaluation of phenyl substituted 1H-1,2,4-triazoles as non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 2

A series of disubstituted-1H-1,2,4-triazole derivatives was synthesized with the aim of developing new non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) - a novel and attractive target for the treatment of osteoporosis. 17βHSD2 catalyzes the oxidation of the highly active estrogen 17β-estradiol (E2) and androgen testosterone (T) into the weak estrone and androstenedione, respectively. Inhibition of this enzyme will locally in the bone lead to an increase in E2 and T levels, two key players in the maintenance of the balance between bone resorption and bone formation. In this study, a new class of 17βHSD2 inhibitors with a 1H-1,2,4-triazole scaffold was identified; the three best compounds 8b, 8f, and 13a showed moderate 17βHSD2 inhibitory activity and a good selectivity toward 17βHSD1. They could be a useful tool to map the unexplored enzyme active site.     

Orally active cephalosporins. I. Synthesis and structure-activity relationships of 7 beta-[2-(R)-amino-2-phenylacetamido]-3-(1H- 1,2,3-triazol-4-yl)alkylthiomethyl-3-cephem-4-carboxylic acid and related compounds]

The synthesis, antibacterial activity and oral absorbability of 7 beta-[2-(R)-amino-2-phenylacetamido]-3-(1H-1H-1,2,3-triazol- 4-yl)methylthiomethyl-3-cephem-4-carboxylic acid (1a) and related compounds (1b-p and 2) are described. The replacement of 1,2,3-triazole at the C-3 position of 1a with other heteroaromatics such as 1,2,4-triazole, imidazole and so on decreased its oral absorbability in mice (1b-j). The oral absorbability was also influenced by the spacer length between C-3 of cephem nucleus and C-4 of 1,2,3-triazole. The quantitative relationship between the bioavailability and the spacer length of cephalosporins (1a and 1k-p) is discussed. These results suggest that 1,2,3-triazole in the side chain at the C-3 position of cephems plays an important role in good oral absorption through its interaction with the transport system of small intestine.     

Synthesis, antitumor and antiviral properties of some 1,2,4-triazole derivatives

A series of 1,5-dialkyl-1,2,4-triazole derivatives of acetic acid alkylidene hydrazides 8-12, the acid 13, 1,5-dialkyl-3-(5-mercapto-4-N-aryl-1H-[1,2,4]-triazol-3-ylmethylene)-1H-[1,2,4] triazoles 14-16, their 1,3,4-oxadiazole analogues 17-21, as well as the 1,2,4-triazolo-indoles 25 and 27 were prepared. The Z/E conformations of some acetic acid alkylidene derivatives were studied by NMR spectroscopy. Most of the target compounds were evaluated in a series of human cancer cell in cultures and none have shown activity except 25 which exhibited remarkable activity against nine cancer types. No in vitro antiviral activity against HIV-1, HIV-2, HSV-1, HSV-2, SV, CV-B4, RSV, P3V, RV, SinV, PTV has been found for all the synthesized compounds.     

Synthesis and biological evaluation of 3-biphenyl-4-yl-4-phenyl-4H-1,2,4-triazoles as novel glycine transporter 1 inhibitors

We describe the preparation and evaluation of a novel series of glycine transporter 1 (GlyT1) inhibitors derived from a high-throughput screening hit. The SAR studies resulted in the discovery of 3-biphenyl-4-yl-4-(2-fluorophenyl)-5-isopropyl-4H-1,2,4-triazole (6p). A pharmacokinetic study was also conducted and revealed that 6p had excellent oral bioavailability and ameliorated learning impairment in passive avoidance tasks in mice.     

Studies on 1,2,4-triazole derivatives as potential anti-inflammatory agents

The reaction of acetic or propionic acid hydrazides with various aryl/alkyl isothiocyanates gave thiosemicarbazides which furnished the 1,2,4-triazoles by alkali cyclization. The 4-aryl/alkyl-5-(1-phenoxyethyl)-3-[N-(substituted)acetamido]thio-4H-1,2,4-triazole derivatives were synthesized by reacting the triazoles with 2-chloro-N-(substituted)acetamide. The chemical structures of the compounds were elucidated by IR, (1)H-NMR, FAB(+)-MS spectral data and elemental analysis. In the pharmacological studies, anti-inflammatory activities of these compounds have been screened and significant activities were observed.