48-[3-(4-amino-5-hydroxy-4,6-dimethyloxan-2-yl)oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-(2-amino-2-oxoethyl)-5,15-dichloro-2,18,32,35,37-pentahydroxy-19-[[4-methyl-2-(methylazaniumyl)pentanoyl]amino]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylate

• 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
• 英文名称: 48-[3-(4-amino-5-hydroxy-4,6-dimethyloxan-2-yl)oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-(2-amino-2-oxoethyl)-5,15-dichloro-2,18,32,35,37-pentahydroxy-19-[[4-methyl-2-(methylazaniumyl)pentanoyl]amino]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylate
• 化学式: C66H75Cl2N9O24
• 分子量: 1449.2
• InChiKey: MYPYJXKWCTUITO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  101
• 可旋转键数：
  12
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  538
• 氢给体数：
  18
• 氢受体数：
  25

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：有限的信息表明，万古霉素在乳汁中产生低水平，因为万古霉素口服吸收不良，不太可能达到婴儿的血液循环或对哺乳婴儿产生任何不良影响。不需要特别的预防措施。 ◉ 对哺乳婴儿的影响：截至修订日期，未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，未找到相关的已发布信息。

◉ Summary of Use during Lactation:Limited information indicates that vancomycin produces low levels in milk and because vancomycin is poorly absorbed orally, it is not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants. No special precautions are required. ◉ 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

• 副作用

哮喘 - 由吸入刺激性或过敏原物质引起的可逆性支气管收缩（支气管小管狭窄）。

Asthma - Reversible bronchoconstriction (narrowing of bronchioles) initiated by the inhalation of irritating or allergenic agents.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

万古霉素与麻醉剂的联合使用已与过敏样反应以及输注反应（例如，低血压、潮红、红斑、荨麻疹、瘙痒）的频率增加有关。在接受万古霉素和麻醉剂的同时治疗的儿科患者中，出现了红斑和类似组胺的潮红。如果在诱导麻醉前1小时给予万古霉素静脉输注，可能会最小化输注相关的不良反应的风险。

Concomitant use of vancomycin and anesthetic agents has been associated with anaphylactoid reactions and an increased frequency of infusion reactions (e.g., hypotension, flushing, erythema, urticaria, pruritus). Erythema and histamine-like flushing has occurred in pediatric patients receiving vancomycin and anesthetic agents concomitantly. The risk of infusion-related adverse effects may be minimized if vancomycin is given as a 1-hour IV infusion prior to induction of anesthesia.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在体外，万古霉素和氨基糖苷类抗生素对许多金黄色葡萄球菌、非肠球菌D群链球菌（牛链球菌）、肠球菌（粪肠球菌）和绿色链球菌的抗菌作用具有协同作用。然而，万古霉素和氨基糖苷类抗生素的联合使用与耳毒性和/或肾毒性的风险增加有关。

In vitro, the antibacterial effects of vancomycin and aminoglycosides are synergistic against many strains of Staphylococcus aureus, nonenterococcal group D streptococci (Streptococcus bovis), enterococci (Enterococcus faecalis), and viridans streptococci. However, concomitant use of vancomycin and aminoglycosides is associated with an increased risk of ototoxicity and/or nephrotoxicity.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

由于可能存在累加毒性，其他耳毒性和/或肾毒性药物（例如，氨基糖苷类、两性霉素B、杆菌肽、顺铂、粘菌素、多粘菌素B）与万古霉素的联合或序贯系统性或局部使用需要仔细连续监测肾脏和听觉功能。在接受万古霉素治疗的病人中应谨慎使用这些药物。

Because of the possibility of additive toxicities, the concurrent or sequential systemic or topical use of other ototoxic and/or nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, bacitracin, cisplatin, colistin, polymyxin B) and vancomycin requires careful serial monitoring of renal and auditory function. These drugs should be used with caution in patients receiving vancomycin therapy.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

盐酸万古霉素在大多数患者中不会显著从胃肠道吸收，因此必须通过非肠道给药来治疗全身性感染。口服生物利用度通常小于5%；然而，有限的数据表明，在一些患有结肠炎和/或肾功能不全的患者中，通过肠道或口服给予万古霉素后，可能会产生具有临床意义的血药浓度。

Vancomycin hydrochloride is not appreciably absorbed from the GI tract in most patients and must be given parenterally for the treatment of systemic infections. Oral bioavailability usually is less than 5%; however, limited data suggest that clinically important serum concentrations of the drug may result following enteral or oral administration of vancomycin in some patients with colitis and/or in those with renal impairment.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在肾功能正常的成年人中，接受多次1克剂量的万古霉素（15 mg/kg）通过静脉输液1小时，输液完成后立即的平均血浆浓度约为63微克/毫升，而2小时和11小时后的平均血浆浓度分别约为23和8微克/毫升。当多次给予500毫克剂量的药物通过静脉输液30分钟时，输液后立即的平均血浆浓度约为49微克/毫升，输液后6小时的平均血浆浓度约为10微克/毫升。

In adults with normal renal function who received multiple 1 g doses of vancomycin (15 mg/kg) given by IV infusion over 1 hour, mean plasma concentrations immediately after completion of the infusion are approximately 63 ug/mL and mean plasma concentrations 2 and 11 hours later are approximately 23 or 8 ug/mL, respectively. When multiple 500-mg doses are given by IV infusion over 30 minutes, mean plasma concentrations are about 49 ug/mL immediately following the infusion and about 10 ug/mL 6 hours after infusion.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

静脉注射后，万古霉素会分布到乳汁中。口服万古霉素的系统吸收非常低，目前尚不清楚药物在口服给药后是否会分布到人乳中。

Vancomycin is distributed into milk following IV administration. Systemic absorption of oral vancomycin is very low and it is not known whether the drug distributes into human milk following oral administration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

万古霉素容易通过胎盘，并分布到脐带血中。

Vancomycin readily crosses the placenta and is distributed into cord blood.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

万古霉素在大约10到100微克/毫升的血清浓度下，通过超滤法测得的血清蛋白结合率约为55%。静脉注射盐酸万古霉素后，抑制性浓度存在于胸膜、心包、腹水和关节腔积液中；在尿液中；在腹膜透析液中；以及心耳组织中。盐酸万古霉素不易通过正常的脑膜扩散进入脊髓液；但是，当脑膜发炎时，它可以渗透进入脊髓液。

Vancomycin is approximately 55% serum protein bound as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 mcg/mL. After IV administration of vancomycin hydrochloride, inhibitory concentrations are present in pleural, pericardial, ascitic, and synovial fluids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin hydrochloride does not readily diffuse across normal meninges into the spinal fluid; but, when the meninges are inflamed, penetration into the spinal fluid occurs.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  (9H-芴-9-基)-癸基(2-氧代乙基)氨基甲酸甲酯 、 48-[3-(4-amino-5-hydroxy-4,6-dimethyloxan-2-yl)oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-(2-amino-2-oxoethyl)-5,15-dichloro-2,18,32,35,37-pentahydroxy-19-[[4-methyl-2-(methylazaniumyl)pentanoyl]amino]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylate 在 48-[3-(4-amino-5-hydroxy-4,6-dimethyloxan-2-yl)oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-(2-amino-2-oxoethyl)-5,15-dichloro-2,18,32,35,37-pentahydroxy-19-[[4-methyl-2-(methylazaniumyl)pentanoyl]amino]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylate 作用下， 以56的产率得到4,7-二氯呋喃并[2,3-d]吡嗪
  参考文献：
  名称：

  Process for purifying glycopeptide phosphonate derivatives

  摘要：

  本发明揭示了一种用于纯化含有一个或多个磷酸酯基取代基的糖肽的方法，这些糖肽可用作抗菌剂。该方法包括将糖肽衍生物的溶液与含有聚苯乙烯的树脂接触，用水溶液洗脱树脂，并分离纯化的糖肽衍生物。

  公开号：

  US07015307B2
• 作为试剂：
  描述：

  (9H-芴-9-基)-癸基(2-氧代乙基)氨基甲酸甲酯 、 48-[3-(4-amino-5-hydroxy-4,6-dimethyloxan-2-yl)oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-(2-amino-2-oxoethyl)-5,15-dichloro-2,18,32,35,37-pentahydroxy-19-[[4-methyl-2-(methylazaniumyl)pentanoyl]amino]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylate 在 48-[3-(4-amino-5-hydroxy-4,6-dimethyloxan-2-yl)oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-(2-amino-2-oxoethyl)-5,15-dichloro-2,18,32,35,37-pentahydroxy-19-[[4-methyl-2-(methylazaniumyl)pentanoyl]amino]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylate 作用下， 以56的产率得到4,7-二氯呋喃并[2,3-d]吡嗪
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARING GLYCOPEPTIDE PHOSPHONATE DERIVATIVES
  [FR] PROCEDES DE PREPARATION DE DERIVES DU GLYCOPEPTIDE PHOSPHONATE

  摘要：

  本发明涉及制备具有含氨基侧链的糖肽磷酸酯衍生物的过程。其中，几个步骤在单个反应容器中进行，无需分离中间反应产物，从而产生更少的废物，提高了整个过程的效率和产率。

  公开号：

  WO2003029270A2

文献信息

• QUINAZOLINE-2,4-DIONE DERIVATIVES
  申请人：Hubschwerlen Christian

  公开号：US20140171425A1

  公开（公告）日：2014-06-19

  The invention relates to antibacterial compounds of formula (I), wherein R 1 is H, halogen, (C 1 -C 3 )alkyl or (C 1 -C 3 )alkoxy; R 2 is H, halogen, (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy or pyrrolidin-1-yl; R 3 is H, halogen, (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, vinyl or 2-methoxycarbonyvinyl or R 2 and R 3 together with the two carbon atoms which bear them form a phenyl ring; R 4 is H, halogen, (C 1 -C 3 )alkyl or (C 1 -C 3 )alkoxy; and R 5 is H, (C 1 -C 3 )alkyl or cyclopropyl, or R 4 and R 5 form together a —CH 2 CH 2 CH 2 — group; A is the divalent group —CH 2 —, —CH 2 CH 2 —, #—CH(OH)CH 2 —*, #—CH 2 N(R 6 )—* and —CH 2 NHCH 2 —, wherein # indicates the point of attachment to the optionally substituted (quinazoline-2,4-dione-3-yl)methyl residue and * represents the point of attachment to the substituted (oxazolidinon-4-yl)methyl residue; R 6 is H or acetyl; Y is CH or N; and Q is O or S; and salts of such compounds.

  该发明涉及式(I)的抗菌化合物，其中R1为H、卤素、(C1-C3)烷基或(C1-C3)氧烷；R2为H、卤素、(C1-C3)烷基、(C1-C3)氧烷或吡咯烷-1-基；R3为H、卤素、(C1-C3)烷基、(C1-C3)氧烷、乙烯基或2-甲氧羰基乙烯基，或R2和R3与携带它们的两个碳原子一起形成苯环；R4为H、卤素、(C1-C3)烷基或(C1-C3)氧烷；R5为H、(C1-C3)烷基或环丙基，或R4和R5一起形成一个— —基团；A为二价基团—CH2—、— —、#—CH(OH) —*、#— N(R6)—*和— NH —，其中#表示可选择取代的(喹唑啉-2,4-二酮-3-基)甲基残基的连接点，*表示取代的(噁唑烷酮-4-基)甲基残基的连接点；R6为H或乙酰基；Y为CH或N；Q为O或S；以及这类化合物的盐。
• A NEW PEPTIDE DEFORMYLASE INHIBITOR COMPOUND AND MANUFACTURING PROCESS THEREOF
  申请人：KANG Jae Hoon

  公开号：US20100168421A1

  公开（公告）日：2010-07-01

  The present invention relates to the novel antibacterial compounds having potent antibacterial activity as inhibitors of peptide deformylase. This invention further relates to pharmaceutically acceptable salts thereof, to processes for their preparation, and to pharmaceutical compositions containing them as an active ingredient.

  本发明涉及具有强效抗菌活性的新型抗菌化合物，作为肽变形酶抑制剂。该发明还涉及其药用盐，其制备方法，以及含有它们作为活性成分的药物组合物。
• Eflornithine Prodrugs, Conjugates and Salts, and Methods of Use Thereof
  申请人：Xu Feng

  公开号：US20100120727A1

  公开（公告）日：2010-05-13

  In one aspect, the present invention provides a composition of a covalent conjugate of an eflornithine analog with an anti-inflammatory drug. In another aspect, the present invention provides a composition of an eflornithine prodrug. In another aspect, the present invention provides a composition of an eflornithine or its derivatives aspirin salt. In another aspect, the present invention provides methods for treating or preventing cancer using the conjugates or salts of eflornithine analogs or eflornithine prodrugs.

  在一个方面，本发明提供了一种氟硝西汀类似物与抗炎药物的共价结合物的组合物。在另一个方面，本发明提供了一种氟硝西汀前药的组合物。在另一个方面，本发明提供了一种氟硝西汀或其衍生物水杨酸盐的组合物。在另一个方面，本发明提供了使用氟硝西汀类似物或氟硝西汀前药的共轭物或盐来治疗或预防癌症的方法。
• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。
• CHLORO-PYRAZINE CARBOXAMIDE DERIVATIVES WITH EPITHELIAL SODIUM CHANNEL BLOCKING ACTIVITY
  申请人：Parion Sciences, Inc.

  公开号：US20140171447A1

  公开（公告）日：2014-06-19

  This invention provides compounds of the formula I: and their pharmaceutically acceptable salts, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.

  这项发明提供了式I的化合物及其药用盐，可用作钠通道阻滞剂，包含这些化合物的组合物，以及用于这些化合物的治疗方法和用途，以及制备这些化合物的方法。