萘夫西林 | 147-52-4

• 物质功能分类: 化学试剂 - 有机试剂 - 多环化合物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 萘夫西林
• 中文别名: 乙氧萘青霉素；萘夫西林酸；新青霉素III
• 英文名称: naphcillin
• 英文别名: Nafcillin；Unipen；nafcillin sodium；6β-(2-ethoxy-naphthalene-1-carbonylamino)-penicillanic acid；6-(2-Ethoxy-naphth-1-yl-formamino)penicillansaeure；(2S,5R,6R)-6-[(2-ethoxynaphthalene-1-carbonyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
• CAS: 147-52-4
• 化学式: C₂₁H₂₂N₂O₅S
• 分子量: 414.482
• InChiKey: GPXLMGHLHQJAGZ-JTDSTZFVSA-N

物化性质

• 沸点：
  714.1±60.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)
• 物理描述：
  Solid
• 溶解度：
  Soluble
• 稳定性/保质期：
  Following reconstitution of Nallpen piggyback units with sterile water for injection or 0.9% sodium chloride, soln containing 10-20 mg of nafcillin per ml are stable for 72 hr @ room temperature or 14 days when refrigerated @ 2-8 °C. Following reconstitution of Nafcil piggyback units with sterile water for injection or 0.9% sodium chloride, soln containing 10-200 mg/ml are stable for 24 hr @ room temperature or 7 days when refrigerated @ 2-8 °C. Nallpen pharmacy bulk packages of the drug that have been reconstituted with sterile water for injection or 0.9% sodium chloride to a concn of 100 mg/ml are stable for 1 hr @ room temperature or 72 hr when refrigerated @ 2-8 °C; Unipen pharmacy bulk packages that have been likewise reconstituted are stable for 8 hr @ room temperature or 48 hr @ 2-8 °C. Nafcil pharmacy bulk packages that have been reconstituted with sterile water for injection or 0.9% sodium chloride to a concn of 250 mg/ml are stable for 72 hr @ room temperature or 7 days when refrigerated @ 2-8 °C or frozen @ -20 to -10 °C; at concn of 10-200 mg/ml, these soln are stable for 24 hr @ room temperature or 7 days @ 2-8 °C. When reconstituted as directed in 0.9% sodium chloride or 5% dextrose, nafcillin sodium soln prepared from Unipen ADD-Vantage vials are stable for 24 hr @ room temperature.
• 碰撞截面：
  196.1 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

ADMET

代谢

大多数青霉素的生物转化中，肝脏代谢占比不到30%。

Hepatic metabolism accounts for less than 30% of the biotransformation of most penicillins.

来源:DrugBank

代谢

...质子催化的青霉素水解成青霉酸是已有详细记录的...这种反应可被细菌的β-内酰胺酶和哺乳动物的酶催化。/青霉素/

...PROTON-CATALYZED HYDROLYSIS /OF PENICILLINS/ TO YIELD PENICILLOIC ACIDS IS WELL DOCUMENTED...CATALYZED BY BACTERIAL BETA-LACTAMASE & BY MAMMALIAN ENZYMES. /PENICILLINS/

来源:Hazardous Substances Data Bank (HSDB)

代谢

那夫西林在杆菌中产生2-乙氧基-1-萘甲酰胺openicilloic酸。/来自表格/

NAFCILLIN GIVES 2-ETHOXY-1-NAPHTHAMIDOPENICILLOIC ACID IN BACILLUS. /FROM TABLE/

来源:Hazardous Substances Data Bank (HSDB)

代谢

大约60%的奈夫西林剂量在肝脏中被代谢成无活性的代谢物。

Approx 60% of a dose of nafcillin is metabolized in the liver to inactive metabolites.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 肝毒性

在用高剂量静脉注射苯唑西林治疗期间出现的血清转氨酶升高似乎不会在使用高剂量萘夫西林时出现，那些在使用高剂量苯唑西林时出现血清转氨酶水平升高的患者可以安全地转为静脉注射萘夫西林或其他青霉素类抗生素。只有极少数的明显肝毒性病例与使用萘夫西林有关。通常，这种伤害是胆汁淤积性肝炎，在开始使用萘夫西林后1到6周出现，可能持续较长时间，但最终会解决。皮疹、发热和嗜酸性粒细胞增多不常见，但可能会发生（案例1）。这种伤害与氟氯西林和氯唑西林描述的伤害相似，但在萘夫西林中发生的频率要低得多。自身抗体不常见。

The serum aminotransferase elevations that appear during high dose intravenous therapy with oxacillin do not appear to occur with high doses of nafcillin, and patients who develop elevated serum aminotransferase levels while on high dose oxacillin can be safety switched to intravenous nafcillin or other penicillin antibiotics. Only rare instances of clinically apparent hepatotoxicity have been linked to use of nafcillin. Typically, the injury has been a cholestatic hepatitis that arises 1 to 6 weeks after starting nafcillin and can be prolonged, but ultimately resolves. Rash, fever and eosinophilia are uncommon but can occur (Case 1). The injury is similar to that described with flucloxacillin and cloxacillin but is far less frequent with nafcillin. Autoantibodies are uncommon.

来源:LiverTox

毒理性

• 药物性肝损伤

复方:萘夫西林

Compound:nafcillin

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注解：较少的药物性肝损伤关注

DILI Annotation:Less-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重性等级：3

Severity Grade:3

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：警告和预防措施

Label Section:Warnings and precautions

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

静脉注射500毫克萘夫西林后，平均血浆浓度约为30微克/毫升。这个值在注射后5分钟达到。

Following intravenous administration of 500mg nafcillin, the mean plasma concentration was approximately 30 µg/mL. This value was reached after 5 minutes of injection.

来源:DrugBank

吸收、分配和排泄

• 消除途径

耐夫西林主要通过非肾脏途径消除，即肝脏灭活和胆汁排泄。

Nafcillin is primarily eliminated by non-renal routes, namely hepatic inactivation and excretion in the bile.

来源:DrugBank

吸收、分配和排泄

• 分布容积

耐夫西林据报道在各种体液中广泛分布，包括胆汁、胸水、羊水和滑液。

Nafcillin is reported to be widely distributed in various body fluids, including bile, pleural, amniotic and synovial fluids.

来源:DrugBank

吸收、分配和排泄

口服吸收不规则，无论是随餐服用还是空腹服用。经非肠道给药后，奈夫西林的血浆浓度低于等效剂量的奥沙西林。这与奈夫西林较大的表观分布容积有关，这是由于奈夫西林在肝脏及可能其他组织中的选择性隔离所导致的。

...ABSORPTION AFTER ORAL ADMIN IS IRREGULAR...WHETHER...TAKEN WITH MEALS OR ON EMPTY STOMACH. AFTER PARENTERAL ADMIN, PLASMA CONCN OF NAFCILLIN IS LOWER THAN...EQUIV DOSE OXACILLIN. THIS IS ASSOC WITH...LARGER APPARENT VOL DISTRIBUTION OF NAFCILLIN, RESULTING FROM SELECTIVE SEQUESTRATION...IN LIVER & POSSIBLY OTHER TISSUE

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大约90%与血浆蛋白结合。口服剂量的约10%可在尿液中回收。丙磺舒进一步减少尿液中排泄。主要消除途径是胆汁...单次静脉注射剂量的约90%通过胆汁排泄；有一些药物从小肠被重吸收。

...BOUND TO PLASMA PROTEIN TO EXTENT OF ABOUT 90%. ONLY APPROX 10% OF ORAL DOSE...RECOVERABLE IN URINE. PROBENECID FURTHER REDUCES EXCRETION IN URINE. MAJOR CHANNEL OF ELIMINATION...IS BILE...ABOUT 90% OF SINGLE IV DOSE... ACCOUNTED FOR BY BILIARY EXCRETION; THERE IS SOME REABSORPTION OF DRUG FROM SMALL INTESTINE.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  萘夫西林 在 β-lactamase from Bacillus cereus 、 水 作用下， 生成 (2R,4S)-2-[(R)-carboxy-[(2-ethoxynaphthalene-1-carbonyl)amino]methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
  参考文献：
  名称：

  Monitoring bacterial resistance to chloramphenicol and other antibiotics by liquid chromatography electrospray ionization tandem mass spectrometry using selected reaction monitoring

  摘要：

  抗生素抗性是全球日益严重的问题。因此，临床实验室通常检测细菌分离物对多种不同抗生素的敏感性，以确定最有效的治疗抗生素。不幸的是，目前的敏感性实验耗时较长。抗生素抗性通常涉及细菌表达的酶将抗生素化学修饰成无活性形式。选定的反应监测（SRM）能够在空前的时间尺度上快速监测和识别这些化学变化。在这项工作中，我们使用SRM作为一种技术来确定几种不同抗生素对化学修饰酶β-内酰胺酶和氯霉素乙酰转移酶的敏感性，这些酶是细菌用于赋予对常用抗生素主要类别的抗性的酶。我们还使用这项技术直接监测在含有特定抗生素的肉汤中培养的耐药细菌的效果。因为SRM具有高选择性，并且还可以在一次实验中识别多种抗生素的化学变化，SRM有能力在一次实验中检测出对多种抗生素具有抗性的有机体。由于这些原因，使用SRM大大减少了确定有机体对多种抗生素的敏感性或抗性所需的时间，因为它消除了目前在其他使用的方法中存在的时间消耗过程。版权所有 © 2013 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jms.3220
• 作为产物：
  描述：

  6β-[(2-ethoxy-naphthalene-1-carbonyl)-phenylacetyl-amino]-penicillanic acid 2-(4-bromo-phenyl)-2-oxo-ethyl ester 在 sodium thiophenolate 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 萘夫西林
  参考文献：
  名称：

  Busko-Oszczapowicz,I. et al., Roczniki Chemii, 1974, vol. 48, p. 253 - 261

  摘要：

  DOI：

文献信息

• [EN] DERIVATIVES OF AMANITA TOXINS AND THEIR CONJUGATION TO A CELL BINDING MOLECULE<br/>[FR] DÉRIVÉS DE TOXINES D'AMANITES ET LEUR CONJUGAISON À UNE MOLÉCULE DE LIAISON CELLULAIRE
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2017046658A1

  公开（公告）日：2017-03-23

  Derivatives of Amernita toxins of Formula (I), wherein, formula (a) R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R 10, X, L, m, n and Q are defined herein. The preparation of the derivatives. The therapeutic use of the derivatives in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.

  Amernita毒素的衍生物的化学式（I），其中，化学式（a）中的R 1、R 2、R 3、R 4、R 5、R 6、R 7、R 8、R 9、R 10、X、L、m、n和Q在此处被定义。这些衍生物的制备。这些衍生物在靶向治疗癌症、自身免疫性疾病和传染病中的治疗用途。
• [EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020257998A1

  公开（公告）日：2020-12-30

  Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

  提供了一种将细胞毒性药物与一个侧链连接分子结合的共轭物。它提供了制备细胞毒性分子与细胞结合配体的共轭物的侧链连接方法，以及在靶向治疗癌症、感染和免疫性疾病中使用该共轭物的方法。
• [EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020006722A1

  公开（公告）日：2020-01-09

  A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.

  一种新型的交联细胞毒剂，吡咯苯并二氮杂环二聚体（PBD）衍生物，以及它们与细胞结合分子的结合物，一种制备这些结合物的方法以及这些结合物的治疗用途。
• [EN] ANTIBACTERIAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIBACTÉRIENS
  申请人：MASSACHUSETTS GEN HOSPITAL

  公开号：WO2019199979A1

  公开（公告）日：2019-10-17

  The present application provides compounds of formula: Methods of using these compounds for killing bacterial growth and treating bacterial infections are also provided.

  本申请提供了以下化合物的公式：还提供了使用这些化合物杀灭细菌生长和治疗细菌感染的方法。
• [EN] HETEROCYCLIC AMIDES USEFUL AS PROTEIN MODULATORS<br/>[FR] AMIDES HÉTÉROCYCLIQUES UTILES EN TANT QUE MODULATEURS DE PROTÉINE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017175147A1

  公开（公告）日：2017-10-12

  Disclosed are compounds having the formula (I-N), wherein q, r, s, A, B, C, RA1, RA2, RB1, RB2, RC1, RC2, R3, R4, R5, R6, R14, R15, R16, and R17, are as defined herein, or a tautomer thereof, or a salt, particularly a pharmaceutically acceptable salt, thereof.

  揭示了具有化学式（I-N）的化合物，其中q、r、s、A、B、C、RA1、RA2、RB1、RB2、RC1、RC2、R3、R4、R5、R6、R14、R15、R16和R17如本文所定义，或其互变异构体，或其盐，特别是其药用可接受盐。