N2-芳基三嗪青霉素和N2-苯基-N4-烷基(芳基)三嗪青霉素的合成及其抗菌活性

设计合成了十个N²-芳基三嗪青霉素和六个N²-苯基-N⁴-烷基(芳基)三嗪青霉素,这十六个化合物均为未见文献报道的新化合物,元素分析数据和光谱数据证实了它们的结构。初步体外抑菌试验表明,十六个化合物对G(+)菌和G(-)菌均有一定的活性,其中的五个化合物具有一定程度的广谱特征。     

N~2-芳基三嗪酰基头孢烯酸和N~2-芳基三嗪酰基-3-氮杂环硫甲基头孢菌素类衍生物的合成

合成了二十个未见文献报道的N~2-芳基三嗪酰基头孢烯酸和N~2-芳基三嗪酰基-3-氮杂环硫甲基头孢菌素衍生物,经元素分析、IR和~4H-NMR等数据的测定,证实了它们的化学结构,运用HPLC法测定和计算了化合物的油水分配系数,初步探讨了油水分配系数P与抗菌活性之间的关系;测定了二十个化合物对二十种革兰氏阳性和阴性菌的最小抑菌浓度(MICμg/ml),其中化合物C_1、C_2、C_3、C_4、C_5所对应的二钠盐JLP15、16、17、18、19具有一定的广谱特征,特别是对青霉素耐药菌株和甲氧西林耐药菌株都显示了一定的活性。     

氨苄青霉素衍生物的合成研究

合成14种未见文献报道的N~2-芳基三嗪酰基氨苄青霉素,通过元素分析、红外和核磁光谱数据确定其化学结构。利用高效液相法测定它们的油水分配系数,采用四种不同菌株初步测定了这些化合物的体外抗菌活性,并探讨这些化合物的油水分配系数与其抗菌活性间的关系。     

头孢来星衍生物的合成研究

本文合成了15个未见文献报道的N~2-芳基三嗪酰基头孢来星和N~2,N~4-双取代芳基三嗪酰基头孢来星。经元素分析、红外和核磁共振光谱数据确定其化学结构.并用高效液相色谱法测定其油水分配系数,采用多种菌株初步测定了这些新化合物的体外抗菌活性,探讨了影响抗菌活性的因素及活性与化合物油水分配系数的关系。     

氨苄青霉素衍生物的合成研究

合成了14种未见文献报道的N~2 -芳基三嗪酰基氨苄青霉素,其中有9种化合物对葡萄球菌有较好活性(MIC=1～5μg/ml);有 8种化合物对绿脓杆菌稍有活性(MIC=50～100μg/ml)。利用HPLC法测定了这14种化合物的油水分配系数。并用已知logp六种芳胺做对照考察logk＇与logp的关系。用logk＇代替logp对这14种化合物的logk＇与其对葡萄球菌和绿脓杆菌的抑菌活性1/C之间的关系进行了探讨。结果表明,这些化合物的logk＇与其对葡萄球菌抑菌活性1/C的关系基本上呈抛物线形式,即当logk＇增大时抑菌活性也随之增强,但logk＇增大至一定值时抑菌活性反而降低; logk＇与绿脓杆菌活性的关系基本上呈下斜线形式,即化合物的logk＇逐渐增大时其活性大为降低。     

7β-N~2-芳基三嗪酰胺基苯乙酰胺基-3-亚甲基杂环头孢烯酸衍生物的合成及其抗菌活性

设计合成了１０个７βＮ２芳基三嗪酰胺基苯乙酰胺基３亚甲基杂环头孢烯酸衍生物及其二钠盐,均为未见文献报道的新化合物,其结构经元素分析数据及光谱分析证实．体外抑菌试验结果表明：化合物（Ⅱ１）,（Ⅱ２）和（Ⅱ３）活性较强,对所选用的１９种菌株均有一定的活性,多数化合物的ＭＩＣ值为８ｍｇ／Ｌ,具有一定的广谱抗菌特征     

3-(氨基烷氧基芳基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物的设计、合成与乙酰胆碱酯酶抑制活性

目的初步探讨在7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物母核C-3位苯环侧链中引入二乙胺基团的3-(氨基烷氧基芳基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物的合成及其乙酰胆碱酯酶抑制活性。方法以取代的苯甲醛和乙酰甘氨酸为初始原料,经Erlenmeyer-Plchl反应、缩合反应、水解反应、缩合反应,生成6-芳甲基-3-硫代-1,2,4-三嗪-5(2H)-酮类化合物,再与取代的α-氯代苯乙酮反应,得到6-芳甲基-3-(羟基芳基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物;以芳基乙烯为原料,经温和的氧化反应、缩合反应得到3,4-二氢-6-芳基-3-硫代-1,2,4-三嗪-5(2H)-酮类化合物,再与取代的α-氯代苯乙酮在乙酸中反应得到6-芳基-3-(羟基芳基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物。两条合成路线得到的3-(羟基芳基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物进一步经Williamson反应制备得到10个3-(烷氧基芳基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物。所有目标化合物结构均经质谱、红外光谱和核磁共振氢谱确证。采用Ellman法对目标化合物进行体外乙酰胆碱酯酶抑制活性筛选。结果根据前期已筛选化合物的活性数据和总结出的初步构效关系,设计并合成了10个C-3位苯环侧链中含有二乙胺基团的3-(氨基烷氧基芳基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物。体外乙酰胆碱酯酶抑制活性筛选表明,所有目标化合物均具有乙酰胆碱酯酶抑制活性,其中7个化合物在10μmol.L-1浓度水平抑制活性超过了50%。结论根据体外重组人源AChE(rhAChE)抑制活性的测试结果,发现C-3位苯环侧链中含有二乙胺基团的7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物均具有较好的rh-AChE抑制活性。在这一位置的侧链中引入二乙胺基团,可以增强化合物对rhAChE的抑制活性。     

3-芳基-6-(溴代芳甲基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物的设计、合成及其乙酰胆碱酯酶抑制活性研究

目的设计合成3-芳基-6-(溴代芳甲基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物,并探讨C-6位芳甲基上引入溴原子对其乙酰胆碱酯酶抑制活性的影响。方法以4-羟基苯甲醛为原料,经溴代反应,得到3-溴-4-羟基苯甲醛和3,5-二溴-4-羟基苯甲醛,再将溴代的4-羟基苯甲醛与乙酰甘氨酸经Erlenmeyer-Plchl反应、水解反应、缩合反应合成目标化合物3-芳基-6-(溴代芳甲基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物。采用Ellman法对目标化合物进行体外乙酰胆碱酯酶抑制活性筛选。结果所有目标化合物的结构均经红外光谱、质谱和核磁共振氢谱确证。目标化合物经体外乙酰胆碱酯酶抑制活性筛选,结果显示:所有目标化合物均具有乙酰胆碱酯酶抑制活性,其中8个化合物在10μmol.L-1浓度水平抑制活性超过了40%。结论在7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物母核C-6位芳甲基中引入溴原子的3-芳基-6-(溴代芳甲基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物普遍具有较高的AChE抑制活性,并且引入2个溴原子的化合物抑制活性明显高于引入1个溴原子的化合物。     

三嗪青霉素的合成研究

三嗪青霉素是对绿脓肝菌有优异抗苗活性的广谱半合成青霉素。本文采用水合氧代丙二酸酯代替氧代丙二酸酯,并将其与氨基硫脲缩合,再经环合水解和氧化制成三嗪酸的四步反应改进为“一勺烩”的连续操作法,提高收率27.3%。三嗪酸与羟氨苄青霉素的缩合反应用价廉的氯甲酸乙酯代替氯甲酸异丁酯,提高了收率。又采用三嗪酸的琥珀酰亚胺活性酯对羟氨苄青霉素进行的酰化反应也获成功。     

三嗪青霉素及其N~2-芳基衍生物的合成研究

三嗪青霉素(BL P 1908,Trizinocillin,I)*是1978年美国开发的广谱半合成青霉素,它对绿脓杆菌有良好的抗菌活性。体外试验其对绿脓杆菌的MIC为2μg/ml,较羧苄青霉素的活性大32～64倍,因而受到重视,但三嗪青霉素对某些革兰氏阳性细菌的抑菌活     

Synthesis and preliminary pharmacological investigation of the central action of derivatives of 3-aminomethyl-5-(p-chlorophenyl)-tetrahydrofuran-2-one and 2-aminomethyl-4-(p-chlorophenyl)-4-hydroxybutyric acid

Using 3-cyano-5-(p-chlorophenyl)-tetrahydrofuran-2-one 4, 3-aminomethyl derivatives of 5-(p-chlorophenyl)-tetrahydrofuran-2-one were synthesized. The starting material under alkaline hydrolysis yielded 5-(p-chlorophenyl)-tetrahydrofuran-2-one-3-carboxylic acid 5, which was transformed, via an acid chloride, into amide 6. From acid 5 by aminomethylation compounds 7-12 were obtained. Some of them (7, 8, 12) in reactions of ammono-, amino-, and hydrazinolysis yielded corresponding derivatives of 2-aminomethyl-4-(p-chlorophenyl)-4-hydroxybutyric acid 13-20. In pharmacological tests compounds 10 displayed analgesic activity while compounds 2 and 3 revealed anxiolytic properties.     

N~1-(4-取代氨基-6-甲基-2-嘧啶基)-N~3-(对氯苯基)胍类的合成及其抗丝虫作用

报道了 N~1-[4-[3-(二烷胺基)甲基-和3,5-双[(二烷胺基)甲基]-4-羟基苯基]氨基]-6-甲基-2-嘧啶基]-N~3-(4-氯苯基)胍的合成。所合成的10个化合物进行了药理初筛,其中8个对感染沙鼠的棉鼠丝虫微丝蚴或成虫显示一定的杀灭作用。     

Synthesis of 7-hydroxy-4-Oxo-4H-chromene- and 7-hydroxychroman-2-carboxylic acidN-alkyl amides and their antioxidant activities

A series of 7-hydroxy-4-oxo-4H-chromene- (3a - h) and 7-hydroxychroman-2-carboxylic acid N-alkyl amides (4a - g) were synthesized and their antioxidant activities were evaluated. While compounds 3a - h were less active, compounds 4a - g exhibited more potent inhibition of lipid peroxidation initiated by Fe2+ and ascorbic acid in rat brain homogenates. Among them, 7-hydroxychroman-2-carboxylic acid N-alkylamides (4e - g) bearing nonyl, decyl, and undecyl side chain exhibited 3 times more potent inhibition than trolox (1).     

Synthesis of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid derivatives of potential anti-inflammatory activity

A series of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid derivatives 4-10 were synthesized by rearrangement of 4-(3-pyridyl)-hydrazono-2-phenyl-2-oxazolin-5-one 3 in the presence of different nucleophiles to afford derivatives 4, 7, and 8, while hydroxamic acid derivative 6 was prepared from reaction of methyl ester 4 with hydroxylamine hydrochloride. Semicarbazide 9 and thiosemicarbazide 10, derivatives of the 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid, were synthesized via hydrazide 8 with potassium cyanate and appropriate isothiocyanate, respectively. The structures of the synthesized compounds were confirmed by elemental analyses, IR, (1)H-NMR, and mass spectra. The results of the anti-inflammatory activity of the synthesized derivatives showed that most of the tested compounds 4-10 showed significant inhibition against carrageenan-induced rat paw edema in albino rats. Derivatives 4 and 8 showed promising results and were found to be equipotent or more potent than Indomethacin and Celecoxib as reference drugs at two dose levels, 5 and 10 mg/kg, and they have no ulcerogenic activity.     

大丁草中抗菌活性成分的研究Ⅳ

从秋季采收的菊科植物大丁草Gerbera anandria(L.)Sch Bip.全草中共分出十三种成分。本文报道其中三个新化合物的结构鉴定.它们分别是3,8-dihydroxy-4-methoxy-coumarin(ⅪⅩ),3,8-dihydroxy-4-methoxy-2-oxo-2 H-1-benzopyran-5-carboxylic acid(ⅩⅦ),和5,8-dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3-)-coumarin(ⅩⅪ)。     

N~1-(4-取代氨基-6-三氟甲基-2-嘧啶基)-N~3-(卤苯基)胍的合成及其抗丝虫作用

报道了N~1-[4＇-[3-(二烷胺基)甲基和3, 5-双[(二烷胺基)甲基]-4-羟基苯胺基]-6-三氟甲基-2-嘧啶基]-N~3-(4-卤苯基)胍的合成。合成了24个化合物,经药理初筛表明,该类型化合物对感染沙鼠的棉鼠丝虫微丝蚴或成虫有一定的杀灭作用。     

薤中抗凝和抗癌活性成分的结构鉴定

从百合科葱属植物薤(Alium chinense)鳞茎的抗凝和抗癌活性部位中,分离得到了6个化合物。经过化学方法和光谱分析(IR,EI-MS,¹HNMR,¹³HNMR,¹H-¹HCOSY,HMBC,HMQC和NOESY谱),鉴定它们的结构分别为(25R,S)-5α-spirostane-3β-ol 3-O-｛β-D-glucopyranosyl-(1→2)-[β-D-glucopyra-nosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside｝(1),(25R,S)-5α-spirostane-3β-ol 3-O-｛β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)](6-acetyl-β-D-glucopyranosyl)-(1→4)-β-D-galac-topyranoside｝(2),(25R,S)-5α-spirostane-2α,3β-diol3-O-｛β-D-glucopyranosyl-(1→2)-O-β-D-glucopyra-nosyl-(1→4)-β-D-galactopyranoside｝(3),(25S)-24-O-β-D-glucopyranosyl 3β,24β-dihydroxy-5α-spirost-3-O-α-arabinopyranosyl-(1→6)-β-D-glucopyranoside(4),chinenosideI(5)及2,3,4,9-tetrahydro-1-methyl-1H-pyrido[3,4-b]indole-3-carboxylicacid(6)。化合物4为一新的甾体皂甙,命名为chinenosideVI。化合物1～3为3对甾体皂甙差向异构体。其中,化合物2的25S型异构体为首次报道;25R型异构体和化合物6为首次从本种植物中分得。此外,通过NOESY谱还首次确定了化合物6的相对构型,并对其C和H信号进行了确切归属。     

Investigations on the synthesis and pharmacological properties of amides of 7-methyl-3-phenyl-1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-2,4- dioxo-1,2,3,4-tetrahydropyrido[2,3-d]-pyrimidine-5-carboxylic acid

Synthesis of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4- tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acid (6-10) and their 1-[2-hydroxy-3(4-phenyl-1-piperazinyl)propyl] derivatives (11-15) are described. Some of them displayed strong analgesic activity.     

Studies on quinolone antibiotics. III. Synthesis and antibacterial activity of 5-amino-7-(2-aminoalkoxy)-1-cyclopropyl-6-fluoro-1,4- dihydro-4-oxoquinoline-3-carboxylic acid and their derivatives]

5-Amino-7-(2-aminoalkoxy)-1-cyclopropyl-6-fluoro-1,4-dihydro-4- oxoquinoline-3-carboxylic acid and their derivatives (10, 11) were prepared and their antibacterial activities were evaluated. As a result of in vitro antibacterial screening, the compounds having mono- or di-methyl (11d, e) group at alpha-position of amino group were most effective among the 7-aminoalkoxy derivatives. Structure-activity relationship of these compounds is also discussed.