(11Z,13Z)-6-[4-(dimethylamino)-3,5-dihydroxy-6-methyloxan-2-yl]oxy-7-[2-(3,5-dimethylpiperidin-1-yl)ethyl]-16-ethyl-4-hydroxy-15-[(5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl)oxymethyl]-5,9,13-trimethyl-1-oxacyclohexadeca-11,13-diene-2,10-dione

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (11Z,13Z)-6-[4-(dimethylamino)-3,5-dihydroxy-6-methyloxan-2-yl]oxy-7-[2-(3,5-dimethylpiperidin-1-yl)ethyl]-16-ethyl-4-hydroxy-15-[(5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl)oxymethyl]-5,9,13-trimethyl-1-oxacyclohexadeca-11,13-diene-2,10-dione
• 化学式: C₄₆H₈₀N₂O₁₃
• 分子量: 869.1
• InChiKey: JTSDBFGMPLKDCD-GHEYFECPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  61
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  186
• 氢给体数：
  4
• 氢受体数：
  15

ADMET

代谢

Beulah杂交羔羊单次皮下注射20 mg/kg bw/天的(14)C-替米考星。肝脏、肾脏和尿液中主要的放射性成分是母药，以及较少的T1和T2，还有少量的其他未识别物质。

Beulah cross lambs were administered a single subcutaneous dose of 20 mg/kg bw per day (14)C-tilmicosin. The major radioactive component in the liver, kidneys and urine was the parent drug, together with lesser amounts of T1 and T2, and minor amounts of other unidentified substances.

来源:Hazardous Substances Data Bank (HSDB)

代谢

费希尔-344大鼠（10只雄性和10只雌性）每天经口灌胃给予50毫克/千克体重的(14)C-蒂利霉素，持续5天。对粪便中硫酸盐代谢物的粪便放射性进行分析，发现了一种与猪粪便中发现的类似化合物的存在，但没有进行量化。

Fischer-344 rats (10 males and 10 females) were given gavage doses of 50 mg/kg bw per day (14)C-tilmicosin for 5 days. An analysis of fecal radioactivity for the presence of the sulfate metabolite that was found in the feces of pigs revealed the presence of a similar compound, but quantification was not undertaken.

来源:Hazardous Substances Data Bank (HSDB)

代谢

替米考星，在去甲基大环内酯环和哌啶环上均标记有（14）C，通过口服给与15只雄性和15只雌性Fischer-344大鼠。剂量为每天20毫克/千克体重，连续3天。在肝脏中，放射性标记对应于替米考星和一个去甲基衍生物，T1（在大环内酯环中去甲基化）。尿液中检测到的单一放射性物质是未改变的替米考星，而在粪便中，主要的峰是母化合物，其次是较少量的去甲基替米考星和一个高分子量化合物，这种化合物已知是给药物质中的杂质，T2（由两个大环内酯环和一个哌啶环组成）。

Tilmicosin, labelled with (14)C in both the desmycosin macrolide ring and the piperidine ring, was given orally to 15 male and 15 female Fischer-344 rats. The dosage was 20 mg/kg bw per day for 3 days. In the liver, radiolabel corresponded to tilmicosin and a desmethyl derivative, T1 (demethylated in the mycaminose ring). The single radioactive substance identified in urine was unchanged tilmicosin, while in feces the major peak was parent compound with lesser amounts of desmethyl tilmicosin and a high molecular weight compound known to be present as an impurity in the administered substance, T2 (consisting of two macrolide rings and one piperidine ring).

来源:Hazardous Substances Data Bank (HSDB)

代谢

在给注射了(14)C-替米考星的结果概述中，报道称处理过的老鼠肝脏中的放射性活性轮廓与粪便中的相似。在使用高度纯化的替米考样品处理的动物中，在肝脏中未检测到代谢物T2，这表明其存在是作为药物物质组成部分直接给药的结果。肾脏中的放射性活性基本上以未改变的替米考星形式存在。

In a summary of results obtained in cattle injected with (14)C-tilmicosin, it was reported that the radioactivity profile in the liver of treated rats was similar to that in the feces. In animals treated with a highly purified sample of tilmicosin, metabolite T2 was not detected in the liver, suggesting that its presence was a result of direct administration as a component of the drug substance. Radioactivity in the kidneys was essentially in the form of unchanged tilmicosin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

猪被喂食含有放射性碳-14标记的泰妙菌素的饮食，每天的剂量为400毫克，持续5天。在肝脏和肾脏中，大约60到70%的放射性标记以母药形式存在，还有少量的一级代谢物T1。同样，在尿液和粪便中，泰妙菌素的含量很高，而T1的含量很低。还检测到另一种代谢物，它构成了粪便中14%和尿液中25%的放射性活性，这种代谢物与大环内酯环中一个双键的还原然后硫酸化一致。

Pigs were fed diets containing (14)C-tilmicosin, which resulted in daily doses of 400 mg, for 5 days. Of the radiolabel in liver and kidney, approximately 60 to 70% was in the form of the parent drug and there were small amounts of T1. Similarly in urine and faeces, there were high levels of tilmicosin and low levels of T1. A further metabolite was detected that comprised 14% of faecal and 25% of urinary radioactivity and that was consistent with reduction of one double bond in the macrolide ring followed by sulfation.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

同时使用卡马西平、环孢素、地高辛、己巴比妥、苯妥英或丙戊酸与大环内酯类抗生素，已与这些药物的血药浓度升高有关；建议监测同时给药的药物的血药浓度，以避免中毒。/大环内酯类抗生素/

Concurrent use /of carbamazepine, cyclosporine, digoxin, hexobarbital, phenytoin or valproic acid/ with macrolide antibiotics has been associated with increased serum concentration of these medications; monitoring of serum concentrations of medications administered concurrently is recommended to avoid toxicity. /Macrolide antibiotics/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

黄嘌呤类药物（除二羟丙茶碱外）与macrolides（大环内酯类抗生素）同时使用可能会减少黄嘌呤类药物的肝清除率，导致血清浓度升高和/或毒性增加；在macrolides治疗期间和治疗后，可能需要调整黄嘌呤类药物的剂量。/大环内酯类抗生素/

Concurrent use of the xanthines (except dyphylline) with macrolides may decrease hepatic clearance of xanthines, resulting in increased serum concentrations and/or toxicity; dosage adjustment of the xanthines may be necessary during and after therapy with macrolides. /Macrolide antibiotics/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

同时使用咪达唑仑或三唑仑与 macrolide 类抗生素可能会降低这些药物的清除率，增加咪达唑仑或三唑仑的药理作用。/Macrolide 类抗生素/

Concurrent use /of midazolam or triazolam/ with macrolide antibiotics may decrease the clearance of these medications, increasing the pharmacologic effect of midazolam or triazolam. /Macrolide antibiotics/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

与 macrolide 抗生素同时使用与增加抗凝血作用有关；在接受抗凝药物和 macrolides 同时治疗的患者中应仔细监测凝血酶原时间。/Macrolide 抗生素/

Concurrent administration with macrolide antibiotics has been associated with increased anticoagulant effects; prothrombin time should be monitored carefully in patients receiving anticoagulants and macrolides concurrently. /Macrolide antibiotics/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。密切观察呼吸不足的迹象，如有需要，进行辅助通气。通过非重复呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，并在必要时进行治疗……。监测休克，并在必要时进行治疗……。预防癫痫发作，并在必要时进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

猪在饮食中接受了154毫克或400毫克（14）C-蒂尔米科辛的剂量，这是在连续5天给予相似剂量后的情况。放射性物质的恢复在尿液中为4%到6%，在粪便中为62%到75%。胆汁中检测到放射性物质，但未进行量化。

Pigs were given a dose of 154 or 400 mg (14)C-tilmicosin in the diet following a similar dose given for 5 days. The recovery of radioactivity was 4 to 6% in urine and 62 to 75% in feces. Radioactivity was detected in the bile but was not quantified.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

猪在一天内通过饲料摄入了110毫克（14）C-蒂尔米科辛。放射性物质的回收率在尿液中为15%，在粪便中为80%。

Pigs were administered a dose of 110 mg (14)C-tilmicosin in the diet over the course of one day. The recovery of radioactivity was 15% in the urine and 80% in the feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

替米考星通过皮下注射给药。注射后吸收迅速...

Tilmicosin is administered SC. Absorption after injection is rapid ... .

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Beulah杂交羔羊单次皮下注射20 mg/kg bw/天的(14)C-替米考星。肝脏、肾脏和尿液中主要的放射性成分是母药，以及较少的T1和T2，还有少量其他未识别的物质。

Beulah cross lambs were administered a single subcutaneous dose of 20 mg/kg bw per day (14)C-tilmicosin. The major radioactive component in the liver, kidneys and urine was the parent drug, together with lesser amounts of T1 and T2, and minor amounts of other unidentified substances.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• N-PHENYL-1,1,1-TRIFLUOROMETHANESULFONAMIDE HYDRAZONE DERIVATIVE COMPOUNDS AND THEIR USAGE IN CONTROLLING PARASITES
  申请人：Winzenberg Norman Kevin

  公开号：US20070238700A1

  公开（公告）日：2007-10-11

  Novel N-phenyl-1,1,1-trifluoromethanesulfonamide compounds useful for controlling endo and/or ectoparasites in the environment are provided, together with methods of making the same, and methods of using the inventive compounds to treat parasite infestations in vivo and ex vivo.

  提供了一种用于控制环境中内外寄生虫的新型N-苯基-1,1,1-三氟甲磺酰胺化合物，以及制备这些化合物的方法，以及利用这些创新化合物治疗体内和体外寄生虫感染的方法。
• Compounds that are Analogs of Squalamine, Used as Antibacterial Agents
  申请人：VIRBAC

  公开号：US20180042942A1

  公开（公告）日：2018-02-15

  The invention relates to compounds of formula (I), to the pharmaceutical compositions comprising same, and to the use thereof in the treatment of bacterial, fungal, viral and parasitic infections or in the treatment of cancer in humans or animals. In formula (I), R1 and R2 are as defined in claim 1.

  这项发明涉及公式（I）的化合物，包括相同的药物组成，以及在人类或动物中用于治疗细菌、真菌、病毒和寄生虫感染或治疗癌症的用途。在公式（I）中，R1和R2如权利要求1中定义的那样。
• [EN] SUBSTITUTED HETEROARYL- AND PHENYLSULFAMOYL COMPOUNDS<br/>[FR] COMPOSES HETEROARYLE ET PHENYLSULFAMOYLE SUBSTITUES
  申请人：PFIZER PROD INC

  公开号：WO2005092845A1

  公开（公告）日：2005-10-06

  The present invention is directed at substituted heteroaryl- and phenylsulfamoyl compounds, pharmaceutical compositions containing such compounds and the use of such compounds as peroxisome proliferator activator receptor (PPAR) agonists. PPAR alpha activators, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans. The compounds are also useful for the treatment of negative energy balance (NEB) and associated diseases in ruminants.

  本发明涉及取代杂环芳基和苯基磺酰胺化合物，含有这种化合物的药物组合物以及将这种化合物用作过氧化物酶增殖激活受体（PPAR）激动剂的用途。PPARα激活剂，含有这种化合物的药物组合物以及使用这种化合物提高特定血浆脂质水平，包括高密度脂蛋白胆固醇，并降低其他特定血浆脂质水平，如低密度脂蛋白胆固醇和甘油三酯，从而治疗由高密度脂蛋白胆固醇水平低和/或低密度脂蛋白胆固醇和甘油三酯水平高加重的疾病，如动脉粥样硬化和心血管疾病，在哺乳动物，包括人类中。这些化合物还可用于治疗反常能量平衡（NEB）和反常相关疾病的反刍动物。
• [EN] IMMUNOMODULATING IMINE-OXAZOLINE AZALIDES<br/>[FR] AZALIDES IMMUNOMODULATEURS D'IMINE-OXAZOLINE
  申请人：ZOETIS SERVICES LLC

  公开号：WO2021183759A1

  公开（公告）日：2021-09-16

  Defined herein are immunemodulating Formula (1) compounds wherein R1, R2, R3, and W are as defined herein, stereoisomers thereof, and pharmaceutically acceptable salts thereof; and compositions comprising said compounds. The invention also includes methods for treating an inflammatory and/or immunological disease or disorder in an animal by administering a therapeutically effective amount of a Formula (1) compound, stereoisomer thereof, and a pharmaceutically acceptable salt thereof; or use of said compound of Formula (1 ) to prepare a medicament for treating an inflammatory and/or immunological disease or disorder in an animal.

  本发明定义了免疫调节式(1)化合物，其中R1、R2、R3和W如本文所定义，其立体异构体，以及药学上可接受的盐；以及包含这些化合物的组合物。本发明还包括通过给予动物治疗有效量的式(1)化合物、其立体异构体及药学上可接受的盐，来治疗炎症和/或免疫性疾病或障碍的方法；以及使用式(1)化合物制备用于治疗动物炎症和/或免疫性疾病或障碍的药物的用途。
• [EN] BRIDGED COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS PONTÉS POUR LE TRAITEMENT DES INFECTIONS BACTÉRIENNES
  申请人：MERCK SHARP & DOHME

  公开号：WO2016123146A1

  公开（公告）日：2016-08-04

  Novel bridged compounds are disclosed herein, along with their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antibacterial agents. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating bacterial infections and associated diseases and conditions.

  本文披露了新型的桥接化合物，以及它们的药用盐、水合物和前药。还披露了包含这些化合物的组合物，制备这些化合物的方法以及将这些化合物用作抗菌剂的方法。所披露的化合物、其药用盐、水合物和前药，以及包含这些化合物、盐、水合物和前药的组合物，对治疗细菌感染及相关疾病和症状是有用的。