盐酸他喷他多 | 175591-09-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 盐酸他喷他多
• 中文别名: 3-[(1R,2R)-3-(二甲基氨基)-1-乙基-2-甲基丙基]苯酚盐酸盐；3-((1R,2R)-3-(二甲基氨基)-1-乙基-2-甲基丙基)苯酚
• 英文名称: tapentadol hydrochloride
• 英文别名: 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol hydrochloride；(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol hydrochloride；3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol hydrochloride；[(2R,3R)-3-(3-hydroxyphenyl)-2-methylpentyl]-dimethylazanium;chloride
• CAS: 175591-09-0
• 化学式: C₁₄H₂₃NO*ClH
• 分子量: 257.804
• InChiKey: ZELFLGGRLLOERW-YECZQDJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  23.5
• 氢给体数：
  2
• 氢受体数：
  2

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概要：关于在哺乳期间使用泰潘哒隆的信息很少。由于它具有阿片类药物激动剂活性，因此在哺乳新生儿或早产儿时，最好选择其他药物。新生婴儿似乎对即使是小剂量的麻醉性镇痛剂的影响也非常敏感。监测婴儿是否有过度镇静和呼吸抑制的情况。如果婴儿表现出过度困倦（比平时更甚）、哺乳困难、呼吸困难或软弱无力，应立即联系医生。当停止母亲使用阿片类镇痛剂或停止哺乳时，哺乳婴儿可能会出现戒断症状。 ◉ 对哺乳婴儿的影响：泰潘哒隆的德国制造商报告称，他们收到了4例婴儿暴露于母乳中泰潘哒隆的自发报告，未观察到不良反应。婴儿的年龄和哺乳的程度没有报告。在其中一位母亲的报告中知道剂量，为100毫克，每天两次，经直肠给药。 ◉ 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:Little information is available on the use of tapentadol during breastfeeding. Because it has opioid agonist activity, an alternate drug is preferred, especially while nursing a newborn or preterm infant. Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Monitor infants for excess sedation and respiratory depression. If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped. ◉ Effects in Breastfed Infants:The German manufacturer of tapentadol reports that they received 4 spontaneous reports of infant exposure to tapentadol in breastmilk, with no adverse reactions noted. Neither the age of the infants nor the extent of breastfeeding was reported. The dosage was known in only one of the mothers, which was 100 mg twice daily given rectally. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  盐酸他喷他多 在 氨 作用下， 以 二氯甲烷 、 水 为溶剂， 以16.1 g的产率得到他喷他多
  参考文献：
  名称：

  [EN] TAPENTADOL MALEATE AND CRYSTALLINE FORMS THEREOF
  [FR] MALÉATE DE TAPENTADOL ET FORMES CRISTALLINES ASSOCIÉES

  摘要：

  本文揭示了一种新颖且稳定的托瑞哌酯盐，即托瑞哌酯盐酸盐，以及其多晶形式、制备过程、制药组合物及其制备方法。

  公开号：

  WO2014108514A1
• 作为产物：
  描述：

  他喷他多 在 盐酸 作用下， 以 二氯甲烷 、 异丙醚 为溶剂， 反应 0.5h， 生成 盐酸他喷他多
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARING L-PHENYL-3-DIMETHYLAMINOPROPANE DERIVATIVE
  [FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS DE L-PHÉNYL-3-DIMÉTHYLAMINOPROPANE

  摘要：

  提供了一种制备l-苯基-3-二甲氨基丙烷衍生物的过程，其化学式为I，并通过新颖的中间体制备其药用可接受的盐。

  公开号：

  WO2012038974A1

文献信息

• Active agent prodrugs with heterocyclic linkers
  申请人：Jenkins Thomas E.

  公开号：US09139612B2

  公开（公告）日：2015-09-22

  The embodiments provide prodrug compounds of Formulae I-XVII. The present disclosure also provides compositions, and their methods of use, where the compositions comprise a prodrug compound of Formulae I-XVII that provides controlled release of an active agent. Such compositions can optionally provide a trypsin inhibitor that interacts with the enzyme that mediates the controlled release of an active agent from the prodrug so as to attenuate enzymatic cleavage of the prodrug.

  本发明的实施例提供了I-XVII号化合物的前药。本公开还提供了组合物及其使用方法，其中所述组合物包含能控制释放活性剂的前药化合物I-XVII。这样的组合物可以选择性地提供一种胰蛋白酶抑制剂，该抑制剂与介导前药控制释放活性剂的酶相互作用，从而减弱前药的酶切裂。
• PRODRUGS OF OPIOIDS AND USES THEREOF
  申请人：Franklin Richard

  公开号：US20110190267A1

  公开（公告）日：2011-08-04

  The present invention concerns prodrugs of opioid analgesics and pharmaceutical compositions containing such prodrugs. Methods for providing more consistent pain relief by increasing the bioavailability of the opioid analgesic with the aforementioned prodrugs are provided. The invention also provides for decreasing the adverse GI side effects of opioid analgesics.

  本发明涉及阿片类镇痛药的前药以及含有此类前药的药物组合物。本发明提供了通过前述前药增加阿片类镇痛药的生物利用度，从而提供更一致的疼痛缓解方法。该发明还提供了减少阿片类镇痛药对胃肠道的副作用的方法。
• [EN] NOVEL INTERMEDIATE OF TAPENTADOL<br/>[FR] NOUVEL INTERMÉDIAIRE DE TAPENTADOL
  申请人：SUN PHARMA ADVANCED RES CO LTD

  公开号：WO2015075744A1

  公开（公告）日：2015-05-28

  The present invention relates to novel carbamate intermediate of formula (II), process for its preparation and process for its conversion into 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol, tapentadol and its pharmaceutically acceptable salts.

  本发明涉及公式（II）的新型氨基甲酸酯中间体，其制备方法以及将其转化为3-[(1R,2R)-3-(二甲氨基)-1-乙基-2-甲基丙基]苯酚、替派诺酚及其药用盐的方法。
• [EN] ANALGESIC COMPOUNDS, METHODS, AND FORMULATIONS<br/>[FR] COMPOSÉS ANALGÉSIQUES, PROCÉDÉS, ET FORMULATIONS
  申请人：LILLY CO ELI

  公开号：WO2012100423A1

  公开（公告）日：2012-08-02

  Provided are compounds, and salts thereof, of formula (I): wherein (A) is R1 is hydrogen, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 haloalkyl, C1-C5 alkanol, -(C1-C5 alkyl)phenyl, or phenyl, or a group of the formula -C(O)-R12, where R12 may be C1-C5 alkyl, C1-C5 alkoxy, C1-C5 haloalkyl, C1-C5 alkanol, -(C1-C5 alkyl)phenyl, or phenyl; R2 and R3 are independently hydrogen, C1-C5 alkyl, C1-C5 alkoxy, halogen, C1-C5 haloalkyl, or C1-C5 haloalkoxy; R4 and R5 are independently hydrogen, C1-C5 alkyl, or -(C1-C5 alkyl)phenyl; R6 is hydrogen, hydroxy, or is absent; R7 is hydrogen; R8 and R9 are independently hydrogen or methyl; R10 is hydrogen; R11 is hydrogen or C1-C5 alkyl; or R7 and R10 combine to form -CH2- or -(CH2)2-; or R8 and R9 combine to form a cyclopropyl group with the carbon to which they are attached; or R10 and R11 combine to form -CH2- or -(CH2)3-. Additionally, pharmaceutical formulations and methods of use employing the above compounds are provided.

  提供的是化合物及其盐，其化学式为（I）：其中（A）是R1为氢、C1-C5烷基、C1-C5烷氧基、C1-C5卤代烷基、C1-C5烷醇、-(C1-C5烷基)苯基或苯基，或具有化学式-C(O)-R12的基团，其中R12可以是C1-C5烷基、C1-C5烷氧基、C1-C5卤代烷基、C1-C5烷醇、-(C1-C5烷基)苯基或苯基；R2和R3独立地为氢、C1-C5烷基、C1-C5烷氧基、卤素、C1-C5卤代烷基或C1-C5卤代烷氧基；R4和R5独立地为氢、C1-C5烷基或-(C1-C5烷基)苯基；R6为氢、羟基或不存在；R7为氢；R8和R9独立地为氢或甲基；R10为氢；R11为氢或C1-C5烷基；或R7和R10结合形成-CH2-或-(CH2)2-；或R8和R9结合形成与它们连接的碳原子的环丙基团；或R10和R11结合形成-CH2-或-(CH2)3-。此外，提供了应用上述化合物的药物配方和使用方法。
• [EN] POLYMERIC HYPERBRANCHED CARRIER-LINKED PRODRUGS<br/>[FR] PROMÉDICAMENTS LIÉS À DES EXCIPIENTS POLYMÉRIQUES HYPERBRANCHÉS
  申请人：ASCENDIS PHARMA AS

  公开号：WO2013024048A1

  公开（公告）日：2013-02-21

  The present invention relates to water-soluble carrier-linked prodrugs of formula (I),wherein POL is a polymeric moiety,each Hyp is independently a hyperbranched moiety,each moiety SP is independently a spacer moiety, each L is independently a reversible prodrug linker moiety, m is 0 or 1, each n is independently an integer from 2 to 200 and each x is independently 0 or 1. It further relates to pharmaceutical compositions comprising said water- soluble carrier-linked prodrugs and methods of treatment.

  本发明涉及水溶性载体连接的前药，其化学式为（I），其中POL是聚合物基团，每个Hyp是独立的超支化基团，每个基团SP是独立的间隔基团，每个L是独立的可逆前药连接基团，m为0或1，每个n是独立的整数，范围从2到200，每个x是独立的0或1。此外，还涉及包含所述水溶性载体连接的前药的药物组合物和治疗方法。