5-芳基-1,2-二氢-1-吡咯里嗪酮类化合物的合成及抗炎镇痛作用

目的 研究5-芳基-1，2-二氢-1-吡咯里嗪酮类化合物的抗炎镇痛作用构效关系，寻找高效低毒、具有抗炎镇痛活性的新型吡咯里嗪酮衍生物。方法 以吡咯里嗪酮为母体，设计并合成了5-芳基-1，2-二氢-1-吡咯里嗪酮类化合物。用二甲苯致小鼠耳肿胀法和小鼠醋酸扭体法测定了该类化合物的抗炎及镇痛活性。结果 用两条路线合成了10个目标化合物，经1H-NMR和MS确证其结构。小鼠试验表明，一些所合成的化合物具有明显的抗炎和／或镇痛作用。结论 化合物Ⅲ1及Ⅲ5的抗炎活性优于对照药布洛芬；化合物Ⅲ5的镇痛活性优于对照药布洛芬；其中化合物Ⅲ5的抗炎及镇痛活性均强于对照药布洛芬，值得进一步研究。     

氨基吡咯里嗪酮的制备和异构体的结构鉴定

对1,2-二氢-1-吡咯里嗪酮(1)进行硝化,得到其5,6和7位3种硝基取代物(2)。确证了该3种硝基取代物的结构。经还原,制得了相应的3种氨基-1,2-二氢-1-吡咯里嗪酮类化合物。     

二氢吡咯并吡嗪酮衍生物的合成和抗炎镇痛作用

目的 研究3，4，－二氢吡咯并[1,2-a]吡嗪－1－酮（Ⅱ）类化合物的抗炎镇痛作用构效关系。方法 通过2－吡咯甲酸甲酯与N－氯乙腈的烃基化反应，制得N－氢甲基吡咯－2－甲酸甲酯（Ⅳ），Ⅳ经还原，环合，Friedel-Crafts酰基化反应，生成6－芳酰基－2－甲基－3，4－二氢吡咯并[1,2-a]吡嗪－1－酮类化合物；用小鼠测试了所合成化合物的抗炎镇痛活性。结果与结论 合成了13个目标化合物；小鼠试验表明，一些所合成的化合物具有明显的抗炎和／或镇痛作用，其中，ZP163的作用活性与对照药布洛芬相似。     

二氢吡咯并恶嗪酮衍生物的合成和抗炎镇痛作用

目的 研究（1H）－3，4－二氢吡咯[2,1-c][1,4]恶嗪－1－酮（Ⅲ）类化合物抗炎镇痛作用的构效关系。方法 通过2－吡咯甲酸甲酯与1，2－二溴乙烷N－烃基化反应，制得1－（2－溴乙基）吡咯－2－甲酸甲酯（Ⅳ），经过氧化银处理，得到Ⅲ；通过Friedel-Crafts酰基化反应，合成Ⅲ的6－酰基衍生物Ⅴ1－Ⅴ8；用小鼠测试了所合成的化合物的抗炎镇痛活性。结果与结论 合成了8个目标化合物；药理实验表明，所合成的一些化合物具有明显的抗炎和／或镇痛活性，其中Ⅴ5活性最强。     

二氢吡咯并(口恶)嗪酮衍生物的合成和抗炎镇痛作用

目的研究(1H)-3,4-二氢吡咯[2,1-c][1,4](口恶)嗪-1-酮(Ⅲ)类化合物抗炎镇痛作用的构效关系.方法 通过2-吡咯甲酸甲酯与1,2-二溴乙烷N-烃基化反应,制得1-(2-溴乙基)吡咯-2-甲酸甲酯(Ⅳ),经过氧化银处理,得到Ⅲ;通过Friedel-Crafts酰基化反应,合成Ⅲ的6-酰基衍生物Ⅴ1～Ⅴ8;用小鼠测试了所合成的化合物的抗炎镇痛活性.结果与结论 合成了8个目标化合物;药理实验表明,所合成的一些化合物具有明显的抗炎和/或镇痛活性,其中Ⅴ5活性最强.     

吡咯里嗪化合物的药用研究概况

初步阐明了吡咯里西啶生物碱的药理作用 ,对吡咯里嗪及其衍生物以及 1H 2 ,3 二氢 1 吡咯里嗪酮及其衍生物的药用研究进行了综述 .指出了以 2 ,3 二氢 1 吡咯里嗪或 2 ,3 二氢 1 吡咯里嗪酮作为先导物进行结构修饰与优化、寻找新药的可能性 .     

二氢吡咯并噁嗪酮衍生物的合成和抗炎镇痛作用

目的研究 (1H) 3,4 二氢吡咯 [2 ,1 c][1,4 ]嗪 1 酮 (Ⅲ )类化合物抗炎镇痛作用的构效关系。方法通过 2 吡咯甲酸甲酯与 1,2 二溴乙烷N 烃基化反应 ,制得 1 (2 溴乙基 )吡咯 2 甲酸甲酯 (Ⅳ ) ,经过氧化银处理 ,得到Ⅲ ;通过Friedel Crafts酰基化反应 ,合成Ⅲ的 6 酰基衍生物Ⅴ1～Ⅴ8;用小鼠测试了所合成的化合物的抗炎镇痛活性。结果与结论合成了 8个目标化合物 ;药理实验表明 ,所合成的一些化合物具有明显的抗炎和 /或镇痛活性 ,其中Ⅴ5活性最强。     

氯基吡咯里嗪酮的制备和异构体的结构鉴定

对1,2－二氢－1－吡咯里嗪酮（1）进行硝化,得到其5,6和7位3种硝基取代物（2）。确证了该3种硝基取代物的结构。经还原,制得了相应的3种氨基－1,2－二氢－1－吡咯里嗪酮类化合物。     

含氟咪唑酮系列衍生物的串联合成及其初步药理学研究

目的优化以含氟乙酰丙酸乙酯衍生物为原料一锅法合成3a-三氟甲基-2,3,3a,4-四氢-1H-苯并[d]吡咯[1,2-a]咪唑-1-酮衍生物的方法,并对合成的衍生物进行初步的药理学研究。方法以含氟乙酰丙酸乙酯衍生物与二羰基酯类化合物为原料,通过Claisen酯缩合再脱羧的方法合成3a-三氟甲基-2,3,3a,4-四氢-1H-苯并[d]吡咯[1,2-a]咪唑-1-酮类衍生物。初步药理学研究采用抗戊四唑(pentylenetetrazole,PTZ)实验对大鼠测定药物的抗惊厥活性;采用旋转法测定其神经毒性。结果成功合成5个含氟乙酰丙酸乙酯衍生物,并将其与一系列胺类化合物反应,一锅法合成了22个含氟氮杂双环化合物。初步药理结果显示:2,3,3a,4-四氢-1H-苯并[d]吡咯[1,2-a]咪唑-1-酮的ED50为50μmol/kg,保护指数(protection index,PI)为10.5(PI=TD50/ED50),显示较好的抗惊厥活性。结论本研究优化了反应条件,缩短了反应时间,提高了反应收率,合成的化合物均具有抗惊厥活性和神经毒性。     

环吡咯酮类化合物的合成及其与苯二氮卓受体结合 的活性研究

目的 设计并合成环吡咯酮类化合物,并评价其与苯二氮卓受体的结合活性。方法 根据环吡咯酮类镇静催眠药佐匹克隆(zopiclone)的基本活性结构特征,设计了17个改变酯键侧链的环吡咯酮类化合物。以2,3-吡嗪二酸酐、2-氨基-5-氯吡啶为起始原料,经过5步反应得到目标产物。以苯二氮卓受体拮抗剂氚标氟马西尼([3H] Ro 15-1788)为工具药,氟马西尼为阳性对照药,通过测试所合成化合物与苯二氮卓受体竞争性结合活性,对目标化合物进行了初步的活性评价。结果与结论 合成得到了17个未见文献报道的环吡咯酮类化合物,结构均经MS和1H-NMR确证。活性筛选实验表明,部分化合物表现出一定的活性。     

用激光解吸电离飞行时间质谱快速测定1H-2,3-二氢-1-吡咯里嗪酮衍生物的相对分子质量

采用激光解吸电离飞行时间质谱 (LDI TOF MS)快速测定了 1H 2 ,3 二氢 1 吡咯里嗪酮衍生物相对分子质量 ,初步总结了该类化合物的质谱规律 .实验中不需加入基质 ,实测值与理论计算值相吻合 .     

5,6-二芳基-2,3-二氢-1-吡咯里嗪酮类化合物的合成及抗炎镇痛活性

目的寻找高效低毒、有抗炎镇痛活性的新的吡咯里嗪酮类化合物。方法以二芳基取代杂环类COX-2选择性抑制剂为模板,以吡里酮为母体,设计并合成了5,6-二芳基-2,3-二氢-1-吡咯里嗪酮类化合物。用IR,¹HNMR和MS确定其结构。用二甲苯致小鼠耳肿胀法和小鼠醋酸扭体法测定这些化合物的(po 200mg·kg^-1)抗炎及镇痛活性。结果合成了17个新化合物(1-17)。生物实验结果显示,多数化合物有一定的抗炎和(或)镇痛活性。结论化合物3,8,11,14和15抗炎活性优于对照药布洛芬;化合物9,10和11镇痛活性接近于对照药布洛芬,值得进一步研究。     

N-(双膦羧次甲基)-6-(5-氟-2,4-二氧代-3,4-二氢-2H-嘧啶-1-基)-6-氧代-己酰胺的合成及其初步的骨靶向性研究

目的合成N-（双膦羧次甲基）-6（5-氟-2，4-二氧代3，4-二氢-2H-嘧啶-1-基）-6-氧代-己酰胺，并进行初步体外骨靶向性实验。方法以5-氟尿嘧啶为原料，经硅烷化、缩合、氢解3步合成6-（5-氟-2，4-二氧代-3，4-二氢-2H-嘧啶-1-基）-6-氧代-己酸（2），用二氯亚砜氯化后再与含氨基的偕二膦酸酯偶联，最后再用溴代三甲基硅烷特异性解离掉膦酸酯得到目标化合物L，并采用羟磷灰石晶体吸附实验考察目标物的骨靶向性。结果合成了目标物L，并利用^-1H—NMR、IR和MS进行了结构确证。结论体外骨靶向性实验结果显示目标物L有较好的骨靶向性。     

New thiazolo[4,5-d]pyrimidine derivatives as potential antimicrobial agents

In this study, by starting from ethyl 4-amino-2,3-dihydro-3-phenyl-2-thioxothiazole-5-carboxylate (1), three compounds having 2,3-dihydro-3-phenyl-5-mercapto-6-alkyl/phenyl-2-thioxothiazolo[4,5- d]pyrimidin-7(6H)-one (2a-c) structure and their 5-(4'-nonsubstituted/-substituted benzoylmethyl)thio derivatives (3a-l) were synthesized. The antimicrobial activities of the synthesized compounds were investigated against some bacteria and fungi using the microdilution method. 2,3-Dihydro-3,6-diphenyl-5-(4'-bromobenzoylmethyl)thio-2-thioxothiazolo [4,5-d]pyrimidin-7(6H) one (3k) possessing remarkable activity against Gram-positive bacteria and yeast like fungi was found to be the most active compound in this series.     

Synthesis and antimicrobial evaluation of some new thiazolo[4,5-d] pyrimidines.

In this study, by starting from ethyl 4-amino-2,3-dihydro-3-methyl-2-thioxothiazole-5-carboxylate (1), the compounds having 2,3-dihydro-3-methyl-5-mercapto-6-methyl/ethyl-2- thioxothiazolo[4,5-d]pyrimidin-7(6H)-one (2a, 2b) structure and their 5-(4'-nonsubstituted/-substituted benzoylmethyl)thio derivatives (3a-h) were synthesized. The chemical structures of the compounds were proved by IR, 1H-NMR and elemental analysis data. In vitro antimicrobial activities of the synthesized compounds were investigated against some bacteria and yeasts using the microdilution method. In view of the antimicrobial activity results, a significant inhibitory effect was observed only for compound 2a against Gram-positive bacteria and yeasts, whereas the other compounds had no remarkable activity against the tested microorganisms.     

Anti-inflammatory 2,3-dihydro-1H-pyrrolizines. 10. 6,7-diarylsubstituted 1- and 3- pyrrolizinones (1-DAPON and 3-DAPON)

Antiinnammatory 2,3-Dihydro-1H-pyrrolizines, × 6,7-Diaryl Substituted 1- and 3-Pyrrolizinones (1-DAPON and 3-DAPON) Oxidation of 2,3-dihydro-6,7-diphenyl-lH-pyrrolizine with SeO₂, leads to the pyrrolizinone 2 and the corresponding selenide 3 . Spectral data as well as chemical reactions prove the structure of 2 . An independent synthesis of the isomeric 3-pyrrolizinone 10 is described.     

3H-1,2-二氢-1-吡里酮衍生物的合成

发现3 H-1,2-二氢-1-吡咯里嗪酮具有明显的抗炎镇痛作用。用Friedel-Crafts酰化和Dieckmann缩合等反应制备了该酮的一些衍生物,其中五个未见于文献报道。药理实验证明,这些化合物均有不同程度的抗炎镇痛作用。     

Synthese neuer 7-Benzofuranmethanamine als heterocyclische Analoga des Squalenepoxidasehemmers Butenafine

Synthesis of New 7-Benzofuranmethanamines as Heterocyclic Analogues of the Squalenepoxidase-Inhibitor Butenafine Selected title compounds ( 6a - f , 7a - d ) were synthesized by RedAl^R-reduction of the carboxamides 4a - f and 5a - d , easily available from the corresponding (2,3-dihydro-)7-benzofurancarboxylic acids 1a - f or 2a - d , respectively. For practical reasons, the preparation of the 2,3-dihydro-2-methyl-7-benzofuranmethanamines 6h - k with varied N-substitution by alkylation of the N-methyl-benzofuranmethanamine 6g with preformed aralkylbromides 9a - d was preferred.     

Synthesis, evaluation and structure-activity relationships of 5-alkyl-2,3-dihydroimidazo[1,2-c] quinazoline, 2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-thiones and their oxo-analogues as new potential bronchodilators

With an aim to obtain potent bronchodilators, two series of 5-alkyl-2,3-dihydroimidazo[1,2-c]quinazolines (Va-1), 2,3-dihydroimidazo[1,2-c]quinazolin-5-(6H)-thiones (VIIIa-d) and their oxo-analogues (IXa-d) have been designed. The compounds Va-1 were synthesized by two alternative routes. The former (Method A) based on the dehydrocyclization of 4-(1-hydroxyethyl)-aminoquinazoline (IV) and the latter (Method B) involves the usage of 2-aminobenzonitrile (VI) which on reaction with ethylenediamine leads to the formation of the key intermediate 2-(2-aminophenyl)-4,5-dihydro-1H-imidazoles (VII). Finally the intermediate VII on condensation with different acidanhydrides yielded the title compound V. In general method-A resulted the compound V in quantitatively higher yields. 2,3-Dihydroimidazo[1,2-c]quinazolin-5 (6H)-thiones (VIII) were obtained by condensing VII with carbon disulfide and a further oxidation of VIII gave their corresponding oxo-analogues (IX). The title compounds V, VIII and IX were evaluated for their bronchodilator activity using in vitro and in vivo (standard animal models) methods. All the test compounds exhibited bronchodilatory activity. The structure activity relationship studies indicated good correlation between the nature of the substituent and bronchodilatory activity. In the 5-alkyl substituted compounds V, a longer alkyl chain showed higher bronchodilatory activity. Compounds VIII and IX were found to be less potent and replacement of sulphur with oxygen showed no significant effect on the biological activity. The presence of halogens altered the biological activity in both the series. Among the compounds tested, 9-lodo-5-(n-propyl)-2,3-dihydroimidazo[1,2-c]quinazoline (VI) was found to be the most potent (percentage protection = 87.1%; relative activity = 1.1 compared to the standard aminophylline).     

Synthesis andin vitro evaluation of some novel benzofuran derivatives as potential anti-HIV-1, anticancer, and antimicrobial agents

A novel series of 1-(1-benzofuran-2-yl-ethylidene)-4-substituted thiosemicarbazides (2a-d) along with some derived ring systems: substituted-2,3-dihydro-thiazoles (3a-c, 4a-f) and thiazolidin-4-ones (5a-d and 6a-d), were synthesized. In addition, cyanoacetic acid-(1-benzofuran-2-yl-ethylidene) hydrazide (7) was used to prepare another new series of compounds consisting of substituted pyridin-2(1H)-ones (8a-c); 2-thioxo-2,3-dihydro-thiazoles (9a-d) and 2-thioxo-2,3-dihydro-6H-thiazolo[4,5-d]pyrimidin-7-ones (10a-c, 11a-c). The absolute configuration of compound 5c was determined by X-ray crystallography. The compounds prepared were evaluated for their in vitro anti-HIV, anticancer, antibacterial, and antifungal activities. Among the tested compounds, compounds 5c and 9a produced a significant reduction [symbols, see text] the viral cytopathic effect (93.19% and 59.55%) at concentrations > 2.0 x 10(-4) M and 2.5 x 10(-5) M respectively. Compound 9a was confirmed to have moderate anti-HIV activity. Compounds 2a, 2d, and 5c showed mild antifungal activity. However, none of the tested compounds showed any significant anticancer activity.