ampicillin | 33993-48-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: ampicillin
• 英文别名: L-(+)-Ampicillin；(2S,5R,6R)-6-[(2-amino-2-phenylacetyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
• CAS: 33993-48-5
• 化学式: C₁₆H₁₉N₃O₄S
• 分子量: 349.411
• InChiKey: AVKUERGKIZMTKX-UWFZAAFLSA-N

物化性质

• 熔点：
  205 °C
• 沸点：
  683.9±55.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  138
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ampicillin 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 p-bromophenacyl-6-β-<(4-n-butyl-3-(4,4-dimethyloxazolin-2-yl)-1,4-dihydropyridylmethylcarbonylaminophenylacetyl)amino>-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate
  参考文献：
  名称：

  Dubey; Knaus, Canadian Journal of Chemistry, 1985, vol. 63, # 3, p. 559 - 580

  摘要：

  DOI：
• 作为产物：
  描述：

  bacampicillin hydrochloride 在 水 作用下， 生成 ampicillin
  参考文献：
  名称：

  Stabilization of ampicillin analogs in aqueous solution. VI. Kinetic analysis of the stabilization mechanism of bacampicillin with benzaldehyde in aqueous solution.

  摘要：

  研究表明，氨苄西林盐酸盐（BAPC）在水溶液中按照平行连续反应方案降解，包括直接失活的β-内酰胺断裂反应和通过氨苄西林（ABPC）的反应过程。特别是BAPC的3-羧酸盐的降解比β-内酰胺更快，BAPC在碱性区域（pH 7.00-9.00）中很容易转化为ABPC。然而，由于在这pH范围内添加苯甲醛形成的加合物，β-内酰胺和BAPC酯部分的降解受到抑制。另一方面，在酸性区域（pH<6.00）中没有观察到这种稳定化作用，因为没有形成加合物。加合物的形成常数随着pH的增加而增加。基于上述结果以及从含有BAPC和苯甲醛的碱性溶液制备的冷冻干燥产物的红外和质谱数据，得出加合物是由BAPC的α-氨基和苯甲醛形成的席夫碱；ABPC也会形成类似的加合物。

  DOI：

  10.1248/cpb.33.1202

文献信息

• Synthesis and oral absorption of hetacillin and hetamoxicillin labile esters.
  作者：SANTIAGO GUBERT、CELIA PALACIN、AURELIO SACRISTÁN、JOSÉ A. ORTIZ

  DOI：10.1248/cpb.35.2366

  日期：——

  Nine esters of hetacillin or hetamoxicillin were synthesized as ampicillin and amoxicillin derivatives with the aim of obtaining improved plasma levels after oral administration. Out of these esters, which are devoid of apparent toxic effects, the benzyloxymethyl ester of hetacillin (FI-5204) gave the best result and was chosen for subsequent studies.

  将九种海他西林或海莫西林的酯类作为氨苄西林和阿莫西林的衍生物进行合成，旨在通过口服给药获得更优的血液浓度水平。在这些没有明显毒性效应的酯类中，海他西林的苄氧甲酯（FI-5204）呈现出最佳效果，因此被选作后续研究的对象。
• High performance liquid chromatographic determination and pharmacokinetic investigation of amino-penicillins and their metabolites in man.
  作者：TOYOZO UNO、MIKIO MASADA、KIYOSHI YAMAOKA、TERUMICHI NAKAGAWA

  DOI：10.1248/cpb.29.1957

  日期：——

  The metabolism and pharmacokinetics of amino-penicillins such as ampicillin (AB-PC), hetacillin (IPAB-PC), talampicillin (TA-PC), amoxycillin (AM-PC) and cyclacillin (AC-PC) in man were investigated. An ion-pair reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of parent penicillins and their metabolites in human urine. The time courses of urinary excretions of unchanged penicillins and metabolites (penicilloic acid (PA) and penamaldic acid (PM)) up to 8 hours after oral administration were determined by using the HPLC method. The moment analysis of urinary excretion rate-time curves gave mean residence times and excretion amounts of the various species. The ratios of excreted amounts to dose (500 mg) at infinite time were estimated to be as follows : (1) AB-PC : 29.4% for unchanged AB-PC, 4.3% for AB-PA and 2.0% for AB-PM (total 35.6%) ; (2) IPAB-PC : 51.8% for AB-PC, 8.7% for AB-PA and 3.9% for AB-PM (total 63.9%) ; (3) TA-PC : 68.8% for AB-PC, 10.2% for AB-PA and 4.5% for AB-PM (total 83.5%) ; (4) AM-PC : 58.9% for unchanged AM-PC, 15.6% for AM-PA and 6.9% for AM-PM (total 81.4%) ; and (5) AC-PC : 76.6% for unchanged AC-PC and 13.4% for AC-PA (total 90.0%). AC-PC gave no detectable amount of penamaldic acid. The rate constants for absorption, metabolism, and urinary excretion were estimated from the moments of the time course curves by using a one-compartment open model. The pharmacokinetic features of amino-penicillins and the prodrugs, are compared and discussed.

  研究了人体内氨苄青霉素（AB-PC）、海他西林（IPAB-PC）、他唑西林（TA-PC）、阿莫西林（AM-PC）和环青霉素（AC-PC）的代谢和药代动力学。开发了一种离子对反相高效液相色谱法，用于同时测定人尿中母体青霉素及其代谢物。通过HPLC法测定了口服给药后8小时内未变青霉素和代谢物（青霉素酸（PA）和青霉醛酸（PM））的尿排泄时间过程。尿排泄速率-时间曲线的矩分析给出了各种物种的平均停留时间和排泄量。在无限时间内排泄量与剂量（500 mg）的比率估计如下：（1）AB-PC：29.4%未变的AB-PC，4.3%AB-PA和2.0%AB-PM（总计35.6%）；（2）IPAB-PC：51.8% AB-PC，8.7% AB-PA和3.9% AB-PM（总计63.9%）；（3）TA-PC：68.8% AB-PC，10.2% AB-PA和4.5% AB-PM（总计83.5%）；（4）AM-PC：58.9%未变的AM-PC，15.6% AM-PA和6.9% AM-PM（总计81.4%）；和（5）AC-PC：76.6%未变的AC-PC和13.4% AC-PA（总计90.0%）。AC-PC未检测到青霉醛酸。通过使用单室开放模型，从时间过程曲线的矩估计了吸收、代谢和尿排泄的速率常数。比较并讨论了氨基青霉素和前药的药代动力学特征。
• SELF-ASSEMBLING BIS-UREA COMPOUNDS FOR DRUG DELIVERY
  申请人：Agency For Science, Technology and Research

  公开号：US20150037390A1

  公开（公告）日：2015-02-05

  Cationic, anionic, and/or zwitterionic bis-urea compounds self-assemble by non-covalent interactions in aqueous solution to form high aspect ratio nanofibers. The nanofibers reversibly bind drugs by non-covalent interactions, forming drug compositions for exhibiting sustained release of the drug.

  阳离子、阴离子和/或带电离子双脲化合物在水溶液中通过非共价相互作用自组装成高纵横比纳米纤维。这些纳米纤维通过非共价相互作用可逆地结合药物，形成药物组合物，以实现药物的持续释放。
• Studies on prodrugs. II. Preparation and characterization of (5-substituted 2-Oxo-1,3-dioxolen-4-yl)methyl esters of ampicillin.
  作者：FUMIO SAKAMOTO、SHOJI IKEDA、GORO TSUKAMOTO

  DOI：10.1248/cpb.32.2241

  日期：——

  (5-Substituted 2-oxo-1, 3-dioxolen-4-yl) methyl esters were designed as a new type of ampicillin prodrug. These esters were prepared and confirmed to produce higher blood levels of ampicillin than ampicillin trihydrate itself after oral administration to mice. The compounds which produced particularly high blood levels of ampicillin were found to be hydrolyzed readily in blood in vitro. Ampicillin (5-methyl-2-oxo-1, 3-dioxolen-4-yl) methyl ester hydrochloride (KBT-1585) showed the best oral absorbability in mice.

  (5-取代的2-氧基-1,3-二恶烷-4-基)甲酸酯被设计为一种新型的青霉素前药。这些酯类化合物的制备经过确认，在小鼠口服给药后能产生比青霉素三水合物本身更高的血药浓度。那些能显著提高青霉素血药浓度的化合物在体外血液中容易水解。青霉素（5-甲基-2-氧基-1,3-二恶烷-4-基）甲酸酯盐酸盐（KBT-1585）在小鼠中显示出最佳的口服吸收性。
• Quaternary heterocyclylamino .beta.-lactams: a generic alternative to the classical acylamino side chain
  作者：John Hannah、Charles R. Johnson、Arthur F. Wagner、Edward Walton

  DOI：10.1021/jm00346a024

  日期：1982.4

  beta-[(1-substituted-4-pyridinio)amino]ceph-3-em-4-carboxylates have been found to be interesting new classes of antibacterial beta-lactams, readily available by SN2 Ar coupling of fluoro-substituted quaternized pyridines and appropriate amino lactam carboxylic acids. Compared to penicillin G, the penam 12c exhibited a spectrum extended to Gram-negative species, such as Escherichia, Shigella, Klebsiella

  已经发现6个β-[（（1-取代的4-吡啶基）氨基] penam-3-羧酸酯和7个β-[（（1-取代的4-吡啶基）氨基] ceph-3-em-4-羧酸酯有趣的新型抗菌β-内酰胺类，可以通过SN2 Ar偶合氟取代的季铵化吡啶和合适的氨基内酰胺羧酸来获得。与青霉素G相比，penam 12c的光谱扩展到革兰氏阴性菌，如埃希氏菌，志贺氏菌，克雷伯菌和肠杆菌，被针对革兰氏阳性菌的效力丧失所抵消。除假单胞菌外，许多头孢实例均显示出对上述革兰氏阴性生物的优异活性，在某些情况下，例如15i，该光谱包括对葡萄球菌和链球菌的良好表现。由于有沙雷氏菌和许多变形杆菌，