Study of the interaction of the compounds resulting from the reaction of carbodithiomethyl acid hydrazide with acetic acid. II

N2-carbodithiomethyl-N1-3-carboxycrotonic acid hydrazide (I) was cyclized with acetic acid to (II) and concentrated sulphuric acid to (III). Unstable compound (II) was found to be converted by action concentrated sulphuric acid into compound (III). The obtained compound (III) was subjected to further reactions for preparing new compound.     

Derivates of carbodithiomethyl-carboxycrotonic acids and acetic acid anhydride

N2-carbodithiomethyl-N1-3-carboxycrotonic acid hydrazide (I) was cyclized with acetic acid anhydride to (II). Unstable compound (II) was found to be converted by action dilute acids into compound (III). The obtained compound (III) was subjected to further reactions for preparing new compounds.     

Comparative effect of chemical structure of chlorinated N-hydroxy-N-acyl-aminobiphenyl ethers and their related compounds on rat liver cytosol-catalyzed transacylation

Studies of structure-transacylation relationships for a series of acylhydroxamic acids of chlorinated biphenyl ethers and their related compounds by rat liver N-arylacylhydroxamic acid-dependent N-acyltransferase (AHNAT) are described. In the transacylation of 4-aminoazobenzene catalyzed by AHNAT, 4-substituents (chloro, phenoxy, and mono-, di-, and trichlorophenoxy groups) of N-phenylacetohydroxamic acid enhanced the ability of the unsubstituted hydroxamic acid to serve as acetyl donors. As to the number of chlorines in the phenoxy group, the activity increased with decreasing number from three to zero. Of the monochlorophenoxy compounds, the 4'-chloro compound was the most effective acetyl donor. In 3-substituents (chloro and phenoxy groups) of N-phenylacetohydroxamic acid, the 3-chloro compound was an effective acetyl donor similarly to the 4-chloro compound, whereas the 3-phenoxy compound was 48% as active as the 4-phenoxy compound. None of 2-substituted N-phenylacetohydroxamic acids examined showed transacetylation activity. As to the effect of acyl group structure on the activity, N-propionyl, N-glycoloyl, and N-formyl derivatives of the 4-(4'-chlorophenoxy) compound were only 4, 2, and 0% as active as the corresponding acetyl compound, respectively. Esterification of the N-arylacetohydroxamic acid decreased the activity; O-acetyl, O-methyl, O-glucosyl, and O-glucuronosyl derivatives of the 4-(4'-chlorophenoxy) compound were 35, 7, 0, and 0% as active as the corresponding N-hydroxy compound, respectively.     

Studies on the biotransformation of 5-vinyl-5-(1-methylbutyl)- and 5-vinyl-5-(1-ethyl-propyl)-barbituric acid (author's transl)]

After taking 5-vinyl-5-(1-methylbutyl)-barbituric acid (vinylbital, Speda) another not yet known metabolite (Sp 1) was isolated from urine and was identified as 5-vinyl-5-(1-methyl-3-carboxy-propyl)-bartiburic acid. Compound Sp 2a is 1-methylhydantoin. Presumably this compound is an artifact from creatinine. We have not yet been able to identify a third mercury(I)-nitrate-positive substance Sp 2b. The supposition that this compound were a metabolite of 5-vinyl-5-(1-ethyl-propyl)-barbituric acid could not be upheld. The three mercury(I)-nitrate-positive substances appearing in the urine after taking 5-vinyl-5-(1-ethyl-propyl)-barbituric acid, behaved in chromatographic analysis completely differently from the unknown compound Sp 2b. The substances were isolated. Two of them are the metabolites 5-vinyl-5-(1-ethyl-2-carboxy-ethyl)-barbituric acid and 5-(1-ethyl-propyl)-barbituric acid. We are not sure whether the third compound identified as 5-hydroxy-5-(1-ethyl-propyl)-barbituric acid, is formed in vivo, as the substance could have developed by oxidation or by the influence of peroxide contained in ether, as well. A product hydroxylized in the side chain, like in vinylbital, was not found in the metabolite urine of 5-vinyl-5-(1-ethyl-propyl)-barbituric acid.     

A new tannin-related compound from the rhizome of Polygonum bistorta L

A new tannin-related compound named bistortaside A (1) and a known compound have been isolated from the rhizome of Polygonum bistorta L. A new compound was elucidated as 3-methyl-gallic acid 4-O-beta-d-(6'-O-3'-methyl-galloyl)-glucopyranoside and a known compound was quercetin-3'-O-beta-d-glucopyranoside (2) on the basis of spectroscopic analysis.     

复方烟酸缓释片与烟酸普通片在犬体内药代动力学的比较研究

目的比较复方烟酸缓释片与烟酸普通片中烟酸及其代谢物烟尿酸在Beagle犬体内的药代动力学。方法6只Beagle犬采用随机交叉给药方案,单剂量口服500mg复方烟酸缓释片或烟酸普通片后,用RP-HPLC法同时测定Beagle犬血浆中烟酸及其主要代谢物烟尿酸的药物浓度,计算药动学参数和相对生物利用度。结果Beagle犬单剂量口服500mg复方烟酸缓释片和烟酸普通片后,烟酸主要药代动力学参数tmax分别为(2.17±0.61)h和(1.04±0.49)h,Cmax分别为(30.85±4.50)mg·mL-1和(68.05±20.48)mg·mL-1,t1/2分别为(0.69±0.43)h和(0.43±0.10)h,MRT分别为(2.12±0.62)h和(1.72±0.40)h,AUC0-12h分别为(62.17±21.13)mg·h·L-1和(138.67±44.86)mg·h·L-1;烟尿酸主要药代动力学参数tmax分别为(2.42±0.49)h和(1.50±0.45)h,Cmax分别为(0.76±0.34)mg·mL-1和(1.66±0.63)mg·mL-1,t1/2分别为(1.74±1.24)h和(1.64±1.03)h,MRT分别为(2.42±0.62)h和(1.79±0.38)h,AUC0-12h分别为(1.55±0.76)mg·h·L-1和(3.25±1.16)mg·h·L-1。结论单剂量口服复方烟酸缓释片,测得的Cmax、tmax和AUC与烟酸普通片均有显著性差异,受试缓释片的tmax长于参比普通片,Cmax低于参比普通片,说明受试缓释片无突释现象,有一定缓释效果。     

GLUT1介导的脑靶向去甲文拉法辛前药的设计与合成

目的合成一种由葡萄糖转运蛋白1(GLUT1)介导的脑靶向去甲文拉法辛前药。方法将苄基保护的去甲文拉法辛与己二酸单叔丁酯在缩合剂DCC作用下成酯Ⅱ,经三氟乙酸脱除叔丁基保护后,再与1,2,3,4-四-O-三甲硅基-α-D-吡喃葡萄糖在缩合剂DCC的作用下成酯,在酸性条件下脱除三甲硅基保护,最后催化氢化脱除苄基保护得到目标化合物。结果与结论合成了目标化合物脑靶向去甲文拉法辛前药;目标化合物及重要中间体均经1HNMR和MS确证。     

复方丹参片与滴丸中丹酚酸B和丹参酮Ⅱ_A含量的比较研究

目的:测定并比较复方丹参片与滴丸中丹酚酸B和丹参酮ⅡA的含量。方法:色谱柱为EclipseXDBC18,丹酚酸B、丹参酮ⅡA流动相分别为甲醇-0·2%磷酸溶液(40∶60)、甲醇-水(85∶15),流速为1·0ml/min,柱温为30℃,检测波长为280nm。结果:丹酚酸B和丹参酮ⅡA进样量均在0·1μg~2·0μg范围内与峰面积值呈良好线性关系(r丹酚酸B=0·9998、r丹参酮ⅡA=0·9999);复方丹参片中丹酚酸B、丹参酮ⅡA的平均回收率分别为100·7%(RSD=1·9%)、101·0%(RSD=1·5%),复方丹参滴丸中丹酚酸B、丹参酮ⅡA的平均回收率分别为98·6%(RSD=1·2%)、98·8%(RSD=1·4%)。结论:本方法准确、可靠、重现性好;复方丹参片中丹酚酸B和丹参酮ⅡA含量较高,复方丹参滴丸中则未定量检出上述2成分。     

药师干预对某肿瘤专科医院六合氨基酸注射液合理应用的效果分析

目的:了解药师干预前后某肿瘤专科医院(以下简称"该院")六合氨基酸注射液的合理应用情况,探讨干预效果。方法:采用回顾性调查法,抽取2019年1—3月(干预前)、2019年10—12月(干预后)该院应用六合氨基酸注射液的出院病历各100份,分别从适应证、用法与用量和溶剂等方面进行对比分析。结果:六合氨基酸注射液不合理使用率从干预前的80%(80/100)降至干预后的56%(56/100),干预前后的差异有统计学意义(P<0.05)。干预前,六合氨基酸注射液在适应证、用法与用量和溶剂等方面均存在不合理应用情况,经药师持续干预,上述不合理用药情况均有改善,尤其是用法与用量、溶剂方面改善明显,与干预前的差异均有统计学意义(P<0.05);对适应证不合理情况进行分析,发现主要涉及围术期营养支持,其次为围化疗期营养支持、围放疗期营养支持,干预前后的差异无统计学意义(P>0.05)。结论:药师持续干预有助于促进六合氨基酸注射液的合理应用。     

复方乙酰水杨酸片质量标准研究

目的:完善复方乙酰水杨酸片的质量标准,提高其质量控制水平.方法:采用《中华人民共和国药典》2015年版四部相关方法和拟定标准方法,对复方乙酰水杨酸片拟定的质控项目进行检验,建立复方乙酰水杨酸片的薄层色谱鉴别方法,建立HPLC同时测定HPLC鉴别(1)、游离水杨酸、溶出度、含量均匀度和含量测定的方法,同时以3个主成分为目...     

奥替溴铵的合成研究

目的研究肠易激综合征治疗药奥替溴铵的合成工艺。方法以水杨酸和正溴辛烷为原料经成酯保护、醚化及水解脱保护得到邻辛氧基苯甲酸,将其制成酰氯后与普鲁卡因缩合,再与溴甲烷反应制得目标化合物。结果与结论目标化合物的结构经IR、MS、元素分析和1H-NMR谱确证。合成工艺路线操作比文献报道的方法更简便,成本低,总收率达36.3%（以水杨酸计算）,适合工业化生产。     

氨基葡萄糖与硫酸软骨素复方片的抗炎、镇痛作用

目的将氨基葡萄糖与硫酸软骨素制成复方片剂,考察其抗炎与镇痛作用。方法氨基葡萄糖与硫酸软骨素按5∶4的比例压片制成复方片剂。以SD大鼠为实验动物,建立足趾肿胀模型进行抗急性炎症实验;采用棉球植入法进行抗慢性炎症实验;以ICR小鼠为实验动物,建立小鼠疼痛模型进行镇痛实验。结果给药28 d,足趾肿胀1 h,低、中、高剂量组足趾肿胀度明显小于正常对照组(P<0.05)。大鼠肉芽肿实验结果显示各给药组与正常组相比能明显抑制大鼠肉芽肿(P<0.05)。醋酸致小鼠扭体实验显示各给药组与对照组比较,对醋酸致小鼠扭体次数有明显的抑制(P<0.05)。结论氨基葡萄糖与硫酸软骨素复方片具有抗炎作用;对醋酸致小鼠疼痛模型具有镇痛作用。     

复方乳酸软膏治疗寻常型鱼鳞病随机双盲基质对照多中心临床研究

目的 评价复方乳酸软膏治疗寻常型鱼鳞病的疗效和安全性。方法用随机、基质对照临床试验,共126例,其中试验组62例,对照组64例。局部用药,每日2次,共用4周。结果 客观指标为鳞屑、角化、皲裂,试验组和对照组有效率分別为100.0％和73.3％,主观指标为干燥、瘙痒、疼痛,试验组和对照组有效率分别为98.4％和63.3％。各项指标比较差异均有统计学意义(P<0.001)。药物不良事件仅对照组发生1例,发生率为0.8％,两组比较差异无统计学意义。结论 复方乳酸软膏治疗寻常型鱼鳞病疗效高,安全性好,使用方便。     

(3S,4S)-3-苄氧羰基氨基-4-羟甲基-2-氧代氮杂环丁烷-1-磺酸四丁基铵氨甲酰化的新方法

目的研究氨甲酰化(3S,4S)-3-苄氧羰基氨基-4-羟甲基-2-氧代氮杂环丁烷-1-磺酸四丁基铵(1)的新方法。方法以化合物1为原料,二氯甲烷为溶剂,经氯磺酰异氰酸酯酰化、亚硫酸钠水溶液脱氯磺酰基,再经阳离子交换树脂得目标化合物(3)。结果所得化合物经1HNMR、IR、旋光和元素分析确证。结论所选方法用于化合物1氨甲酰化较理想。     

阿法替尼的合成

对阿法替尼合成工艺进行研究。以4-氟-2-氨基苯甲酸为起始原料,经环合、硝化、氯化、取代反应得到中间体6;中间体6与（S）-3-羟基四氢呋喃经醚化、还原、酰化和取代后得到化合物10（即阿法替尼游离碱）;最后化合物10与马来酸成盐得到目标化合物阿法替尼,总收率约5.4%。     

Ferulic acid dimer inhibits lipopolysaccharide-stimulated cyclooxygenase-2 expression in macrophages

Phenylpropanoids may act as nonsteroidal anti-inflammatory drug (NSAID)-like compounds. 4-cis, 8-cis-Bis (4-hydroxy-3-methoxyphenyl)-3, 7-dioxabicyclo-[3.3.0]octane-2,6-dione (bis-FA, compound 2), a dimer of ferulic acid, was synthesized from ferulic acid (1), and its effect on lipopolysaccharide (LPS)-stimulated cyclooxygenase-2 (COX-2) expression in RAW 264.7 cells was compared with those of the parent ferulic acid (1) and of iso-ferulic acid (3-hydroxy-4-methoxycinnamic acid) (3). LPS-induced gene expression of COX-2 was markedly inhibited by compound 2 at a concentration of 10 microM and by compound 3 at 100 microM, but was not inhibited by compound 1 at 100 microM. This observation suggests that compound 2 may possess potent anti-inflammatory activity. These ferulic acid-related compounds were able to scavenge the stable 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical. The 50% inhibitory concentration for DPPH radicals declined in the order 3 (40.20 mM) > 2 (3.16 mM) > 1 (0.145 mM). Compound 1 possessed potent anti-radical activity, but no COX-2 inhibitory activity, which may be a result of enhancement of its conjugate properties by abstraction of an H atom from the phenolic OH group, causing loss of phenolic function. In contrast, inhibition of COX-2 expression by compounds 2 and 3 could be caused by their increased phenolic function, which is associated with decreased anti-radical activity. Compounds 2 and 3, particularly 2, may have potential as NSAID-like compounds.     

莫达非尼左旋异构体的合成工艺研究

目的 合成新型中枢兴奋药物莫达非尼的左旋异构体。方法 以二苯甲醇和巯基乙酸为起始原料,经缩合、酯化、氧化、水解,得到(±)-二苯甲基亚硫酰基乙酸,用(S)-(-)-α-甲基苄胺拆分得到(-)-二苯甲基亚硫酰基乙酸,再经酯化、氨解,得到目标化合物。结果 目标化合物结构经核磁共振氢谱和质谱确证。结论 该合成方法,原料廉价易得,实验操作简单。     

元宝草的化学成分研究

目的：对元宝草的化学成分进行研究。方法：利用硅胶、聚酰胺、Sephadex LH-20和大孔树脂柱层析对化合物进行分离，并利用光谱技术和理化性质进行结构鉴定。结果：从元宝草乙醇提取液的二氯甲烷萃取物中分离得到5个化合物，鉴定为二十八烷醇（octacosanol，化合物1）、三十烷酸（triacontanoic acid，化合物2）、豆甾醇（stigmasterol，化合物3）、苯甲酸（benzoic acid，化合物4）和1-羟基-7-甲氧基咕吨酮（1-hydroxy-7-methoxy-xanthone，化合物5）；从乙酸乙酯萃取物中分离得到3个化合物，鉴定为没食子酸（3，4，5-trihydroxy-benzoic acid，化合物6）、槲皮素（quercetin，化合物7）和1，3，6，7-四羟基咕吨酮（1，3，6，7-tetrahydroxy-xanthone，化合物8）。结论：除化合物7以外，其余7个化合物均为首次从元宝草中分离得到。     

柱前衍生高效液相色谱法测定复方氨基酸注射液中氨基酸的含量

目的建立以2,4-二硝基氟苯为衍生化试剂,高效液相色谱法(HPLC)测定复方氨基酸注射液(18AA)中各氨基酸含量的方法。方法采用Agilent HC-C 18色谱柱,乙腈-水(60∶40)为流动相A,乙腈-磷酸盐缓冲液(9∶91)流动相B,梯度洗脱,流速1.0 mL·min-1,检测波长360 nm,柱温27℃。结果复方氨基酸注射液中各氨基酸分离度良好,线性相关系数均大于0.9989,平均回收率均在98%~102%之间,RSD%均小于2%。结论本方法可以用于复方氨基酸注射液(18AA)中氨基酸检测。     

CJ-15,183, a new inhibitor of squalene synthase produced by a fungus, Aspergillus aculeatus

A new squalene synthase (SSase) inhibitor, CJ-15,183 (I) was isolated from the fermentation broth of a fungus, Aspergillus aculeatus CL38916. The compound potently inhibited rat liver and Candida albicans microsomal SSases and also inhibited the human enzyme. It also showed antifungal activities against filamentous fungi and a yeast. The structure was determined to be an aliphatic tetracarboxylic acid compound consisting of an alkyl gamma-lactone, malic acid and isocitric acid moieties by spectroscopic studies.