3,14-Dihydroxy-17-cyclobutylmethylmorphinan | 42408-82-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 3,14-Dihydroxy-17-cyclobutylmethylmorphinan
• 英文别名: L-3,14-dihydroxy-N-(cyclobutylmethyl)morphinan；17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene-4,10-diol
• CAS: 42408-82-2；50807-69-7；58115-67-6；58117-34-3；84416-15-9
• 化学式: C₂₁H₂₉NO₂
• 分子量: 327.467
• InChiKey: IFKLAQQSCNILHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用概述：有限的数据表明，布托啡诺以少量分泌进入母乳。布托啡诺口服吸收不良，因此不太可能对哺乳的婴儿产生不利影响。然而，由于没有关于在哺乳期间重复使用、高剂量、静脉或鼻腔给药的布托啡诺的已发表经验，所以在这些情况下可能更倾向于使用其他药物，特别是在哺乳新生儿或早产儿时。监测婴儿是否出现嗜睡、适当的体重增长和发育里程碑，尤其是在较年轻、完全以母乳喂养的婴儿中。与其他阿片类药物一样，一旦母亲的乳汁开始分泌，最好限制母亲的摄入量，并在必要时用非阿片类止痛药补充止痛。如果婴儿表现出过度嗜睡（比平时更甚）、哺乳困难、呼吸困难或无力，应立即联系医生。分娩止痛药可能会延迟哺乳的开始。 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发表信息。 对泌乳和母乳的影响：阿片类药物和阿片激动-拮抗剂可以增加血清催乳素。然而，在已经建立泌乳的母亲中，催乳素水平可能不会影响她的哺乳能力。 一项研究比较了在分娩期间接受布托啡诺或纳布啡的妇女（n = 26）与未接受止痛的妇女（n = 22）。止痛组的有效哺乳时间较长（46.5分钟），而未止痛组的有效哺乳时间为35.4分钟。 一项全国性的调查研究了晚期妊娠至分娩后12个月的妇女及其婴儿，比较了接受和不接受分娩止痛药的母亲的第二次泌乳（lactogenesis II）的时间。药物类别包括仅脊髓或硬脊膜外腔给药、脊髓或硬脊膜外腔加另一种药物，以及其他止痛药。接受任何类别药物的妇女比未接受分娩止痛药的妇女有大约两倍的风险出现第二次泌乳延迟（>72小时）。

◉ Summary of Use during Lactation:Limited data indicate that butorphanol is excreted into breastmilk in small amounts. Butorphanol is poorly orally absorbed, so it is unlikely to adversely affect the breastfed infant. However, because there is no published experience with repeated, high, intravenous or intranasal doses of butorphanol during breastfeeding, other agents may be preferred in these situations, especially while nursing a newborn or preterm infant. Monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants. As with other opioids, once the mother's milk comes in it is best to limit maternal intake and to supplement analgesia with a nonopioid analgesic if necessary for pain control. If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately. Labor pain medication may delay the onset of lactation. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Narcotics and narcotic agonist-antagonists can increase serum prolactin. However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed. A study compared women who received butorphanol or nalbuphine during labor (n = 26) to those who received no analgesia (n = 22). The time to effective breastfeeding was longer (46.5 minutes) in the analgesia group than in the no analgesia group (35.4 minutes). A national survey of women and their infants from late pregnancy through 12 months postpartum compared the time of lactogenesis II in mothers who did and did not receive pain medication during labor. Categories of medication were spinal or epidural only, spinal or epidural plus another medication, and other pain medication only. Women who received medications from any of the categories had about twice the risk of having delayed lactogenesis II (>72 hours) compared to women who received no labor pain medication.

来源:Drugs and Lactation Database (LactMed)

安全信息

• 海关编码：
  2933499030

文献信息

• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF BUTORPHANOL TARTRATE<br/>[FR] PROCÉDÉ DE PRÉPARATION AMÉLIORÉ DE TARTRATE DE BUTORPHANOL
  申请人：HIKAL LTD

  公开号：WO2017168444A1

  公开（公告）日：2017-10-05

  The present invention relates to an improved process for the preparation of Butorphanol tartrate of formula (I),

  这项发明涉及一种改进的制备盐酸布托啡诺的方法，其化学式为(I)。
• Novel Therapeutic Compounds
  申请人：SESHA Ramesh

  公开号：US20120046272A1

  公开（公告）日：2012-02-23

  The present invention describes a series of therapeutically active compounds of formula I, X—Y—Z  (I) that are useful for treating a disorder in a mammal. In the formula I, X and Z, which may be same or different, are independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group or substituted or unsubstituted heterocyclylalkyl; and Y is a linker selected from —O—, —S—, —NH—, —(CH 2 ) n —, —CO—, —CONR a —, —NR a CO—, —NR a COO—, —COO—, —CONR a CO—, —CONR a COO— and —COOCOO—. The compounds are useful to treat neurodegenerative disorders, depression, Alzheimer's disease, cognitive disorders, motor disorders, Parkinson's disease, drug addiction, behavioral disorders, inflammatory disorders, stomach disorders, cancers, acute pain, chronic pain and recurrent pain.

  本发明描述了一系列具有治疗活性的化合物，其化学式为I，X—Y—Z  (I)，适用于治疗哺乳动物中的某种疾病。在化学式I中，X和Z，可以相同也可以不同，独立地选择自取代或未取代的烷基、取代或未取代的烯基、取代或未取代的环烷基、取代或未取代的环烷基烷基、取代或未取代的芳基、取代或未取代的芳基烷基、取代或未取代的杂芳基、取代或未取代的杂芳基烷基、取代或未取代的杂环基团或取代或未取代的杂环烷基；Y是从—O—、—S—、—NH—、—(CH2)n—、—CO—、—CONRa—、—NRaCO—、—NRaCOO—、—COO—、—CONRaCO—、—CONRaCOO—和—COOCOO—中选择的连接基团。这些化合物适用于治疗神经退行性疾病、抑郁症、阿尔茨海默病、认知障碍、运动障碍、帕金森病、药物成瘾、行为障碍、炎症性疾病、胃病、癌症、急性疼痛、慢性疼痛和复发性疼痛。
• Process for the preparation of butorphanol tartrate
  申请人：Hikal Limited

  公开号：US10544101B2

  公开（公告）日：2020-01-28

  The present invention relates to an improved process for the preparation of Butorphanol tartrate of formula (I),

  本发明涉及一种制备式（I）酒石酸布托诺啡的改进工艺、
• AN IMPROVED PROCESS FOR THE PREPARATION OF BUTORPHANOL TARTRATE
  申请人：Hikal Limited

  公开号：EP3436425B1

  公开（公告）日：2021-01-06
• [EN] NOVEL THERAPEUTIC COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS THÉRAPEUTIQUES
  申请人：GRUENENTHAL GMBH

  公开号：WO2012025213A2

  公开（公告）日：2012-03-01

  The present invention describes a series of novel therapeutically active compounds of formula (I), X-Y-Z that are useful for treating a disorder in a mammal.