4-[(3-酰氨基-4-取代苯基-2-氧-吖丁啶基-1)甲基]-环己甲酸和-苯甲酸的合成及抑制β-内酰胺酶作用

本文设计,并以反式-4-氨甲基环己基田酸和4-氨甲基苯甲酸为原料合成了11种新标题化合物,并经元素分析、红外光谱、核磁共振氢谱和质谱证实。初步抑酶活性测定表明,对腊样芽胞杆菌产生的β-内酰胺酶均有不同程度的抑制作用。     

P-(3-酰氨基-4-取代苯基-2-吖丁啶酮基-1)-苯乙酸和P-(3-酰氨基-4-取代苯基-2-吖丁啶酮基-1)-苯乙酮的合成及抑制β-内酰胺酶作用

为研究吸电子基团远离环氮的单环β-内酰胺类化合物对β-内酰胺酶的抑制作用,设计与合成了21个新的p-(3-酰氨基-4-取代苯基-2-吖丁啶酮基-1)苯乙酸和p-(3-酰氨基-4-取代苯基-2-吖丁啶酮基-1)苯乙酮类化合物,经元素分析、红外光谱、核磁共振氢谱和质谱证实。生物活性测定表明,其中15个具有游离羧基的水溶性化合物对试验的腊样芽胞杆菌和绿脓杆菌产生的β-内酰胺酶有抑制作用。     

P-(3-酰氨基-4-取代苯基-2-吖丁啶酮基-1)-苯乙酸和P-(3-酰氨基-4-取代苯基-2-吖丁啶酮基-1)-苯乙酮的合成及抑制β-内酰胺酶作用

为研究吸电子基团远离环氮的单环β-内酰胺类化合物对β-内酰胺酶的抑制作用,设计与合成了21个新的p-(3-酰氨基-4-取代苯基-2-吖丁啶酮基-1)苯乙酸和p-(3-酰氨基-4-取代苯基-2-吖丁啶酮基-1)苯乙酮类化合物,经元素分析、红外光谱、核磁共振氢谱和质谱证实。生物活性测定表明,其中15个具有游离羧基的水溶性化合物对试验的腊样芽胞杆菌和绿脓杆菌产生的β-内酰胺酶有抑制作用。     

1-(3′,4′-二甲氧基)苯甲酰基-3-酰氨基-4-取代苯基-2-吖丁啶酮类化合物的合成及其抑制β-内酰胺酶的作用

本文设计和合成了14个新的1-(3′,4′-二甲氧基)苯甲酰基-3-酰氨基-4-取代苯基-2-吖丁啶酮类化合物,分别经红外光谱、核磁共振氢谱、质谱和元素分析证实。其中11个化合物具有β-内酰胺酶抑制作用。Ⅶe-1及Ⅶg-1的活性约为临床应用的青霉烷砜酸的两倍。     

Doripenem关键中间体的合成工艺研究

目的合成doripenem关键中间体（2S,4S）-1-叔丁氧羰基-2-（N-叔丁氧羰基-N-氨磺酰）氨甲基-4-琉基毗咯烷，为进一步研究开发奠定基础。方法以反式-4-羟基-L-脯氨酸为原料，经氨基保护、制成混酐、甲磺酰化、硼氧化钠还原、构型反转、Mitsunobu反应、脱乙酰基得到目标化合物。结果目标化合物经红外光谱、核磁共振氢谱和质谱确证其化学结构，总收率达到43．4％。结论本文探索了简便的doripenem侧链的合成工艺，为该工艺用于中试放大提供了依据。     

顺-4-羟甲基-3-苄氧羰酰胺基-2-吖丁啶酮的新合成方法

报道单环β-内酰胺抗生素重要中间体4-羟甲基-β-内酰胺(2)的新合成方法。用 Dane 盐(3)与Schiff 碱(4)加成环合法先制得4-苯乙烯基-β-内酰胺(5),再经四氧化锇-高碘酸钠氧化断裂双键,继经硼氢化钠还原而得4-羟甲基-β-内酰胺(2)。本文对环合、脱保护等各步反应条件进行了改进。总收率以 Schiff 碱计算为12%。     

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。     

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。     

7-甲氧基-4-(2-甲基-4-喹唑啉基)-3,4-二氢喹噁啉-2(1H)-酮的合成工艺改进

目的:改进7-甲氧基-4-(2-甲基-4-喹唑啉基)-3,4-二氢喹噁啉-2(1H)-酮的合成工艺。方法:以2-甲基-4(3H)-喹唑啉酮为起始原料,通过氯代、亲核取代、二芳胺烷基化和硝基还原环合等反应对7-甲氧基-4-(2-甲基-4-喹唑啉基)-3,4-二氢喹噁啉-2(1H)-酮的合成工艺进行改进,并考察其收率。结果:7-甲氧基-4-(2-甲基-4-喹唑啉基)-3,4-二氢喹噁啉-2(1H)-酮的结构经核磁共振氢谱和电喷雾质谱确证,总收率为43.5%,较改进前的20.2%提高了23.3%。结论:改进后的工艺更简单,条件更温和,适合实验室研究的批量制备。     

4-S-(5-酰氨基-1,3,4-噻二唑-2-基)-4-脱氧-4′-去甲基表鬼臼毒素衍生物的合成与抗肿瘤活性

基于在4′-去甲基表鬼臼毒素母核C_4位上联结含有杂原子的芳香环取代基,以此考察其结构与活性关系的设想,设计并合成了10个标题化合物。体外L_(1210)白血病细胞与KB细胞生长抑制试验结果表明,这类化合物有较强的抗肿瘤活性。其中化合物SIPI-92-1772,1774,1775,1776,1777与1779的活性超过临床用药依托泊甙。其余化合物活性与依托泊甙相当或略低。     

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.     

Synthesis and antileukemic activity of new 3-(1-phenyl-3-methylpyrazol-5-yl)-2-styrylquinazolin-4(3H)-ones

3-(1-Phenyl-3-methylpyrazol-5-yl)-2-styrylquinazolin-4(3H)-ones 14a-q and 15a-q were synthesized by refluxing in acetic acid the corresponding 2-methylquinazolinones 12 and 13 with the opportune benzoic aldehyde for 12 h. The synthesized styrylquinazolinones 14a-q and 15a-q were tested in vitro for their antileukemic activity against L1210 (murine leukemia), K562 (human chronic myelogenous leukemia) and HL60 (human leukemia) cell lines showing in some cases good activity.     

4-(4-苯基哌嗪-1-基)-3-O-甲基-D-肌醇的制备及镇咳活性

右旋肌醇甲醚经缩酮制化得3-O-甲基-1，2：5，6-二-O-异亚丙基-D-肌醇，经甲磺酰化、水解、与4-苯基哌嗪缩合制得左羟丙哌嗪类似物4-（4-苯基哌嗪-1-基）-3-O-甲基-D-肌醇，总收率38％。镇咳药效实验表明，目标物对致咳小鼠的镇咳作用明显，但不及左羟丙哌嗪。     

4-(2-溴乙酰基)-3-氟苯硼酸的制备

4-溴-2-氟苯基氰经格氏反应得到4-溴-2-氟苯乙酮,先保护羰基,再经格氏反应和二羟硼基取代、溴代制得4-(2-溴乙酰基)-3-氟苯硼酸,总收率54%.     

α-甲基-4-(3-氧-2H-1,2-苯并异硒唑-2-基)苯乙酸的体外抗氧活性

A synthetic seleno-organic compound, α-methyl-4-(3-oxo-2H-1,2-benzoisoselenazol-2-yl) benzeneacetic acid (MBBA) inhibited the lipid peroxidation of rat liver microsome induced by cysteine/Fe²⁺ and NADPH/Fe²⁺, the IC₅₀ (95% confidence limits) values were 12.2(3.8-39.6) and 7.1(2.5-20.3) μmol·L^-１ respectively. Furthermore, it showed a glutathione peroxidase like activity in vitro. However MBBA (2-100 μmol·L^-１) had no direct inhibition on the production of superoxide anions (O^-₂) and hydroxy radical. Our data suggest that MBBA is a novel inhibitor of lipid peroxidation. Its antioxidant effect may be attributed to glutathione peroxidase like activity. The direct free radical quenching activity of MBBA is ruled out.     

Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate is a novel positive modulator of GABAA receptors

Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate (TG41) enhanced the binding both of gamma-aminobutyric acid (GABA) and of flunitrazepam to rat cerebral cortical membranes. Electrophysiological recordings from Xenopus oocytes expressing various recombinant GABA(A) receptor subtypes revealed that TG41 enhanced the function of all receptor subunit combinations tested. The potency of TG41 at receptors containing alpha1, beta2, and gamma2L subunits was greater than that of alphaxalone, etomidate, propofol, or pentobarbital. The potency of TG41 was also greater at receptors containing alpha1 or alpha2 subunits than at those containing alpha4 and it was markedly higher at receptors containing beta2 or beta3 subunits than at those containing beta1. This drug induced a reversible loss of the righting reflex in Xenopus tadpoles and it elicited hypnosis (5 mg/kg) after intravenous administration in rats. These results indicate that the pharmacological profile of TG41 is similar to that of general anesthetics which potentiate the activity of GABA(A) receptors containing the beta2 or beta3 subunit.     

2-〔4(s)-4-酚胺基-3-氧代-2-异噁唑烷基〕-5-氧代-2-四氢呋喃甲酸钠类化合物的合成

以L-丝氨酸和α-酮戊二酸为原料,采用三条合成路线,经6～8步反应,合成8个目标化合物。其部份中间体的结构经IR,PMR,MS及元素分析证实。产物的结构也经IR及PMR证实。体外抑菌试验表明,TM7和TM8显示较强的广谱抑菌活性,TM6则具有中等强度。TM2和TM3对金葡菌也有一定活性。     

家兔尿中SFZ-47及其两种主要代谢产物的HPLC定量方法

建立了家兔尿中ＳＦＺ－４７及其两种主要代谢产物ＳＦＺ－４７羧基衍生物（Ｍ１）及该衍生物的酯型β－Ｄ－葡糖苷酸（Ｍ２）的 ＨＰＬＣ测定方法，并用该法对单剂量口服２３０ｍｇ ＳＦＺ－４７的 ３只家兔尿样进行了定量分析．结果表明：在０～２４ｈ内，ＳＦＺ－４７，ＭＩ和Ｍ２的累积排泄量分别占给药剂量的（８．３±０．４８）％，（１８．９３±２．６６）％和（２３．４２±８．００）％．