甲氧西林 | 61-32-5

• 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: 甲氧西林
• 英文名称: methicillin
• 英文别名: Meticillin；methicilline；mcthicillin；methycillin；methicilin；methicilln；(2S,5R,6R)-6-[(2,6-dimethoxybenzoyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
• CAS: 61-32-5
• 化学式: C₁₇H₂₀N₂O₆S
• 分子量: 380.422
• InChiKey: RJQXTJLFIWVMTO-TYNCELHUSA-N

物化性质

• 沸点：
  640.0±55.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)
• 物理描述：
  Solid
• 溶解度：
  3.10e-01 g/L
• 稳定性/保质期：
  Reconstituted solutions of methicillin sodium may gradually darken to a deep orange and acquire a distinctive hydrogen sulfide odor upon standing at room temperature for several days. Following reconstitution with sterile water for injection or 0.9% sodium chloride, methicillin sodium solutions containing 500 mg/ml are stable for 24 hours at room temperature, 4 days when refrigerated at 2-8 °C, or 4 weeks when frozen at -20 °C. Longer periods of stability have been reported. In one study following reconstitution with sterile water for injection, solutions containing 500 mg/ml were stable for 71 days when frozen at -16 °C. Once thawed, stabilities of these solutions are the same as those of the unfrozen solutions. /Methicillin sodium/

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  7

ADMET

代谢

肝脏（20-40%）。

Hepatic (20-40%).

来源:DrugBank

代谢

产生2,6-二甲氧基苯基青霉酸在大肠杆菌中。/来自表格/

YIELDS 2,6-DIMETHOXYPHENYLPENICILLOIC ACID IN BACILLUS. /FROM TABLE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：婴儿通过母乳摄入的甲氧西林量很小，预计不会引起任何不良反应。偶尔有报道称使用青霉素会破坏婴儿的胃肠道菌群，导致腹泻或鹅口疮，但这些影响尚未得到充分评估。甲氧西林在哺乳期母亲中是可以接受的。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Amounts of methicillin ingested by the infant in breastmilk are small and would not be expected to cause any adverse effects. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with penicillins, but these effects have not been adequately evaluated. Methicillin is acceptable in nursing mothers. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

甲氧西林钠可能与某些药物在物理和/或化学上不兼容，包括氨基糖苷类和四环素类，但兼容性取决于多个因素（例如，药物浓度、使用的特定稀释剂、结果的pH值、温度）。

Methicillin sodium is potentially physically and/or chemically incompatible with some drugs, including aminoglycosides and tetracyclines, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature). /Methicillin sodium/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

青霉素与氨基糖苷类药物在体外混合会导致显著的相互灭活；如果这些抗生素要同时使用，应该在不同的部位给药，至少间隔1小时。/青霉素/

Mixing penicillins with aminoglycosides in vitro has resulted in substantial mutual inactivation; if these groups of antibacterials are to be administered concurrently, they should be administered at separate sites at least 1 hour apart. /Penicillins/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

甲氨蝶呤与青霉素类药物同时使用会导致甲氨蝶呤的清除率降低，并可能导致甲氨蝶呤中毒；这被认为是由于肾小管分泌的竞争所致；患者应密切监测；可能需要增加亚叶酸钙的剂量，并延长给药时间。/青霉素类药物/

Concurrent of /methotrexate/ with penicillins has resulted in decreased clearance of methotrexate and in methotrexate toxicity; this is thought to be due to competition for renal tubular secretion; patients should be closely monitored; leucovorin doses may need to be increased and administered for longer periods of time. /Penicillins/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

由于抑菌药物（如氯霉素、红霉素、磺胺类药物或四环素）可能会干扰青霉素在治疗脑膜炎或其他需要快速杀菌效果的情况下的杀菌作用，因此最好避免同时使用；然而，氯霉素和氨苄青霉素有时会同时给儿科患者使用。/青霉素/

Since bacteriostatic drugs /Chloramphenicol, erythromycins, sulfonamides, or tetracyclines/ may interfere with the bactericidal effect of penicillins in the treatment of meningitis or in other situations in which a rapid bactericidal effect is necessary, it is best to avoid concurrent therapy; however, chloramphenicol and ampicillin are sometimes administered concurrently to pediatric patients. /Penicillins/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

口服给药后不被吸收。

Not absorbed following oral administration.

来源:DrugBank

吸收、分配和排泄

甲氧西林不通过口服途径使用，因为它吸收不良且容易被胃酸破坏。当药物通过肌内注射给药时，成年人常规剂量1克后，大约30分钟到1小时达到血浆峰浓度，可检测到超过10微克/毫升的血浆浓度...

METHICILLIN IS NOT EMPLOYED BY ORAL ROUTE BECAUSE IT IS POORLY ABSORBED & READILY DESTROYED BY ACIDIC GASTRIC CONTENTS. WHEN DRUG IS GIVEN IM, PEAK PLASMA CONCN ARE REACHED IN ABOUT 30 MIN-1 HR. AFTER CONVENTIONAL DOSE OF 1 G IN ADULTS, PLASMA CONCN IN EXCESS OF 10 UG/ML ARE DEMONSTRABLE...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...2克/日的剂量可以提供超过20微克/毫升的峰值浓度，并且在4小时后仍有大约8微克/毫升的药物存在。大约40%的甲氧西林在血浆中与蛋白质结合。甲氧西林不易渗透进入脑脊液；然而，在患有脑膜炎的患者中可以检测到显著的药物浓度...药物...在多种体液和组织中分布良好。

...2-G DOSE PROVIDES PEAK CONCN OVER 20 UG/ML, & APPROX 8 UG/ML IS STILL PRESENT AFTER 4 HR. ABOUT 40% OF METHICILLIN IN PLASMA IS BOUND TO PROTEIN. METHICILLIN DOES NOT READILY PENETRATE INTO CSF; HOWEVER, SIGNIFICANT CONCN ARE PRESENT IN PATIENTS WITH MENINGITIS... DRUG...WELL DISTRIBUTED IN VARIOUS BODY FLUIDS & TISSUES.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

甲氧西林以原型从尿液中排出...大约2/3的静脉注射剂量通过这种方式在4小时内消除。...在肾功能衰竭的情况下，甲氧西林在血浆中持续存在的时间较长，且浓度较高。...注射的甲氧西林中有一部分无法在尿液中检测到，这部分通过胆汁排出，并随粪便消除。

METHICILLIN IS EXCRETED UNCHANGED IN URINE...ABOUT 2/3 OF IM DOSE IS ELIMINATED BY THIS ROUTE IN 4 HR. ... METHICILLIN PERSISTS FOR LONG PERIOD & @ HIGH CONCN IN PLASMA IN CASES OF RENAL FAILURE. ... PORTION OF INJECTED METHICILLIN THAT CANNOT BE DETECTED IN URINE IS EXCRETED INTO BILE & IS ELIMINATED BY WAY OF FECES.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

最近显示能积极穿过人类胎盘的药物包括...甲氧西林钠... /甲氧西林钠/

DRUGS RECENTLY SHOWN TO ACTIVELY CROSS HUMAN PLACENTA INCL...SODIUM METHICILLIN... /METHICILLIN SODIUM/

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

甲氧西林是一种窄谱β-内酰胺抗生素，通过抑制青霉素结合蛋白(PBPs)发挥作用。它对其他青霉素耐药的金黄色葡萄球菌和表皮葡萄球菌具有活性。甲氧西林常用于治疗皮肤感染、骨髓炎和心内膜炎等疾病。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  6-氨基青霉烷酸	6-Aminopenicillanic Acid	551-16-6	C8H12N2O3S	216.261
  ——	6-aminopenicillanic acid trimethylsilyl ester	1025-55-4	C11H20N2O3SSi	288.443

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	methicillin methyl ester	22668-52-6	C18H22N2O6S	394.448
  ——	6β-(2,6-dimethoxy-benzoylamino)-1,1-dioxo-1λ6-penicillanic acid	76350-41-9	C17H20N2O8S	412.42
  青霉素V	penicilin V	87-08-1	C16H18N2O5S	350.395

反应信息

• 作为反应物：
  描述：

  甲氧西林 在 水 作用下， 生成 2-(2,6-dimethoxybenzamido)acetic acid
  参考文献：
  名称：

  Isomerization and Decomposition Products of Methicillin¹

  摘要：

  DOI：

  10.1021/jo01030a038
• 作为产物：
  描述：

  6-氨基青霉烷酸 以 氯仿 为溶剂， 生成 甲氧西林
  参考文献：
  名称：

  Glombitza,K.-W., Justus Liebigs Annalen der Chemie, 1964, vol. 673, p. 166 - 170

  摘要：

  DOI：

文献信息

• Cobalamin conjugates for anti-tumor therapy
  申请人：Weinshenker M. Ned

  公开号：US20050054607A1

  公开（公告）日：2005-03-10

  The present invention provides a cobalamin-drug conjugate suitable for the treatment of tumor related diseases. Cobalamin is indirectly covalently bound to an anti-tumor drug via a cleavable linker and one or more optional spacers. Cobalamin is covalently bound to a first spacer or the cleavable linker via the 5′-OH of the cobalamin ribose ring. The drug is bound to a second spacer of the cleavable linker via an existing or added functional group on the drug. After administration, the conjugate forms a complex with transcobalamin (any of its isoforms). The complex then binds to a receptor on a cell membrane and is taken up into the cell. Once in the cell, an intracellular enzyme cleaves the conjugate thereby releasing the drug. Depending upon the structure of the conjugate, a particular class or type of intracellular enzyme affects the cleavage. Due to the high demand for cobalamin in growing cells, tumor cells typically take up a higher percentage of the conjugate than do normal non-growing cells. The conjugate of the invention advantageously provides a reduced systemic toxicity and enhanced efficacy as compared to a corresponding free drug.

  本发明提供了一种适用于治疗肿瘤相关疾病的钴胺素-药物结合物。钴胺素通过可切割的连接剂间接共价结合到抗肿瘤药物上，还可以通过一个或多个可选的间隔物。钴胺素通过其核糖环的5'-OH与第一间隔物或可切割连接剂共价结合。药物通过其现有或添加的功能基团与可切割连接剂的第二间隔物结合。在给药后，结合物与转钴胺素（其任何同工异构体）形成复合物。然后，该复合物结合到细胞膜上的受体并被细胞摄取。一旦进入细胞，细胞内酶将切割结合物，从而释放药物。根据结合物的结构，特定类别或类型的细胞内酶影响切割。由于生长细胞对钴胺素的需求量较高，肿瘤细胞通常摄取结合物的比例高于正常非生长细胞。本发明的结合物与相应的游离药物相比，具有较低的全身毒性和增强的疗效。
• Method of producing conjugate vaccines
  申请人：Finn Nicholas

  公开号：US20080213297A1

  公开（公告）日：2008-09-04

  The present invention relates to a method of production of a hydrazide modified sugar comprising a step of reacting a sugar with a hydrazide in a reaction solvent at a pH of between 3 and 5.5, wherein the solvent comprises an aqueous based solvent and an optional polar organic co-solvent. A further aspect of the invention relates to a method of production of a polysaccharide epitope carrier protein conjugate comprising the steps of: (a) reacting a polysaccharide epitope with a hydrazide to form a hydrazide modified polysaccharide epitope; (b) reacting the hydrazide modified polysaccharide epitope with a linker that has been pre-coupled to a carrier protein. Another aspect of the invention relates to a method of production of a sugar-dihydrazide-aldehyde adduct comprising the steps of: (a) producing a hydrazide modified sugar using a method according to the invention, wherein the hydrazide modified sugar includes a further unreacted hydrazide moiety; and (b) reacting the further hydrazide moiety with the aldehyde functionality of a linker group.

  本发明涉及一种生产含有肼改性糖的方法，包括在反应溶剂中将糖与肼在pH值在3至5.5之间反应的步骤，其中溶剂包括水基溶剂和可选的极性有机共溶剂。该发明的另一个方面涉及一种生产多糖表位载体蛋白共轭物的方法，包括以下步骤：(a)将多糖表位与肼反应，形成肼改性多糖表位；(b)将肼改性多糖表位与预先偶联到载体蛋白上的连接剂反应。该发明的另一个方面涉及一种生产糖-二肼-醛加合物的方法，包括以下步骤：(a)使用根据本发明的方法生产肼改性糖，其中肼改性糖包括进一步未反应的肼基团；(b)将进一步的肼基团与连接剂基团的醛功能基团反应。
• [EN] OXAZOLIDINONE COMPOUNDS AND METHODS OF USE THEREOF AS ANTIBACTERIAL AGENTS<br/>[FR] COMPOSÉS OXAZOLIDINONE ET PROCÉDÉS D'UTILISATION DE CES DERNIERS EN TANT QU'AGENTS ANTIBACTÉRIENS
  申请人：MERCK SHARP & DOHME

  公开号：WO2017066964A1

  公开（公告）日：2017-04-27

  The present invention relates to oxazolidinone compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, E, and R1 are as defined herein. The present invention also relates to compositions which comprise at least one oxazolidinone compound of the invention. The invention also provides methods for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial infections by Mycobacterium tuberculosiscomprising administering a therapeutically effective amount of an oxazolidinone of the invention and/or apharmaceutically acceptable salt thereof, or a composition comprising such compound and/or salt.

  本发明涉及式(I)的噁唑烷酮化合物及其药学上可接受的盐，其中A、E和R1如本文所定义。本发明还涉及包含本发明至少一种噁唑烷酮化合物的组合物。该发明还提供了抑制分枝杆菌细胞生长的方法，以及通过给予治疗有效量的本发明的噁唑烷酮和/或其药学上可接受的盐，或包含该化合物和/或盐的组合物来治疗结核分枝杆菌感染的方法。
• [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。