[4-(二甲氨基)-3-甲基-1,2-二苯基丁烷-2-基]丙酸酯 | 77-50-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: [4-(二甲氨基)-3-甲基-1,2-二苯基丁烷-2-基]丙酸酯
• 英文名称: dextropropoxyphene
• 英文别名: Dextropropoxyphen；propoxyphene；l-Propoxyphene；[4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate
• CAS: 77-50-9
• 化学式: C₂₂H₂₉NO₂
• 分子量: 339.478
• InChiKey: XLMALTXPSGQGBX-UHFFFAOYSA-N

物化性质

• 熔点：
  75.5°C
• 沸点：
  475.43°C (rough estimate)
• 密度：
  1.0751 (rough estimate)
• 保留指数：
  2186.5

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用总结：哺乳期母亲口服麻醉剂可能会导致婴儿昏睡，严重的中枢神经系统抑制。新生婴儿似乎对即使是很小的剂量的丙氧芬也非常敏感，可能会特别容易导致这些效果。在哺乳期间应避免使用丙氧芬。 对哺乳婴儿的影响：在一项对12名足月哺乳新生儿进行的情况对照研究中，这些新生儿在出生后第一周出现了无法解释的呼吸暂停、心动过缓或发绀，确定母亲口服丙氧芬是可能的原因。与未发生这些症状的新生儿相比，使用阿片类药物（包括丙氧芬）进行产后镇痛的母亲所生的婴儿中，出现症状的比例更高，分别为83%和31%。受影响的新生儿母亲平均服用的剂量也更高，平均为10剂（范围4至22剂），而对照组为5剂（范围1至13剂）。 一名足月哺乳婴儿在10天大时出现轻度肌张力低下和哺乳困难；到这个时候，婴儿还没有恢复出生时的体重。7天后，母亲的乳汁减少并停止哺乳。婴儿的母亲在产后前10天被开出了每天6粒丙氧芬30毫克加扑热息痛500毫克的处方。从婴儿的头发样本中检测出了丙氧芬和去丙氧芬，且浓度高于母亲头发样本的浓度。丙氧芬可能是婴儿不良反应的原因。 法国一家药物警戒中心汇编了1985年1月至2011年6月间报告的所有哺乳婴儿的不良反应。在174份报告中，丙氧芬被报告在11名婴儿中引起不良反应，并且是在严重不良反应中最常被怀疑的药物之一。反应包括肌张力低下、呼吸暂停、呼吸窘迫、心动过缓、便秘和体重下降。 对泌乳和母乳的影响：麻醉剂可以增加血清催乳素。然而，对于已经建立泌乳的母亲来说，催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:Maternal use of oral narcotics during breastfeeding can cause infant drowsiness, and severe central nervous system depression. Newborn infants seem to be particularly sensitive to the effects of even small dosages of propoxyphene may be particularly prone to causing these effects. Propoxyphene should be avoided during breastfeeding. ◉ Effects in Breastfed Infants:In a case-control study of 12 breastfed term newborns with unexplained episodes of apnea, bradycardia or cyanosis during the first week of life, maternal oral propoxyphene use was determined to be the probable cause. A higher proportion of newborns with episodes, 83 compared to 31%, had mothers using opiates, including propoxyphene, for postpartum analgesia. The mean number of doses taken was also higher with mothers of affected newborns taking a mean of 10 doses (range 4 to 22) compared to 5 doses (range 1 to 13) in the control group. A fullterm breastfed infant had mild hypotonia and nursing poorly at 10 days of age; the infant had not regained her birth weight by this time. By 7 days later, the mother had less milk and stopped nursing. The infant's mother had been prescribed 6 capsules daily of propoxyphene 30 mg plus acetaminophen 500 mg for the first 10 days postpartum. Hair samples from the infant were positive for propoxyphene and norpropoxyphene and were higher than the mother's hair sample concentrations. Propoxyphene was probably the cause of the adverse reactions in the infant. All adverse reactions in breastfed infants reported in France between January 1985 and June 2011 were compiled by a French pharmacovigilance center. Of 174 reports, propoxyphene was reported to cause adverse reactions in 11 infants and to be one of the drugs most often suspected in serious adverse reactions. Reactions included hypotonia, apnea, respiratory distress, bradycardia, constipation and weight loss. ◉ Effects on Lactation and Breastmilk:Narcotics can increase serum prolactin. However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  [4-(二甲氨基)-3-甲基-1,2-二苯基丁烷-2-基]丙酸酯 、 碘甲烷 生成 trimethyl-(2-methyl-3,4-diphenyl-3-propanoyloxybutyl)azanium;iodide
  参考文献：
  名称：

  KIDWELL D. A.; ROSS M. M.; COLTON R. J., SECONDARY ION MASS SPECTROM. SIMS 5. PROC. 5 INT. CONF., WASHINGTON, DC.,+

  摘要：

  DOI：
• 作为产物：
  描述：

  (+)-4-dimethylamino-1,2-diphenyl-3-methyl-2-butanol 、 丙酸酐 生成 [4-(二甲氨基)-3-甲基-1,2-二苯基丁烷-2-基]丙酸酯
  参考文献：
  名称：

  MICHALSKY, J.;STROJIL, L.;KUHR, I.;HRUBY, M.;FERENC, M.;NEMECEK, O.

  摘要：

  DOI：

文献信息

• [EN] DIHYDROPYRROLONAPHTYRIDINONE COMPOUNDS AS INHIBITORS OF JAK<br/>[FR] COMPOSÉS DE DIHYDROPYRROLONAPHTYRIDINONE COMME INHIBITEURS DE JAK
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2010144486A1

  公开（公告）日：2010-12-16

  Disclosed are JAK inhibitors of formula (I) where G1, R1, R2, R3, R4, R5, R6, and R7 are defined in the specification. Also disclosed are pharmaceutical compositions, kits and articles of manufacture which contain the compounds, methods and materials for making the compounds, and methods of using the compounds to treat diseases, disorders, and conditions involving the immune system and inflammation, including rheumatoid arthritis, hematological malignancies, epithelial cancers (i.e., carcinomas), and other diseases, disorders or conditions associated with JAK.

  揭示了式(I)的JAK抑制剂，其中G1、R1、R2、R3、R4、R5、R6和R7在规范中定义。还披露了含有这些化合物的药物组合物、试剂盒和制造物品，制备这些化合物的方法和材料，以及使用这些化合物治疗涉及免疫系统和炎症的疾病、紊乱和症状的方法，包括类风湿关节炎、血液恶性肿瘤、上皮癌（即癌症）和其他与JAK相关的疾病、紊乱或症状。
• [EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
  申请人：MERCK SHARP & DOHME

  公开号：WO2011149801A1

  公开（公告）日：2011-12-01

  The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的萘甲酰胺化合物，它们是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• [EN] QUINAZOLINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] DÉRIVÉS DE QUINAZOLINE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2013181135A1

  公开（公告）日：2013-12-05

  The disclosure relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidases (Nox enzymes) and/or myeloperoxidase.

  该披露涉及喹唑啉衍生物、组合物以及相关方法。在某些实施例中，该披露涉及NADPH-氧化酶（Nox酶）和/或髓过氧化物酶的抑制剂。
• Sustained-release analgesic compounds
  申请人：——

  公开号：US20030022876A1

  公开（公告）日：2003-01-30

  A pharmaceutically active inventive compound comprises two independently active analgesic moieties covalently conjoined through a physiologically labile linker. A preferred embodiment comprises an opioid, such as morphine, covalently linked to at least one analgesic compound selected from the group consisting of an opioid or a non-opioid compound through a physiologically labile linker. Suitable covalent linkers are covalently bonded to the two independently active analgesic compounds through one or more lactone, lactam, or sulfonamido linkages. Suitable linkers include endogenous carboxylate, amido, and sulfonamido moieties, and exogenous moieties that form the aforementioned lactone, lactam or sulfonamido linkages.

  一种药理活性的创新化合物包括通过生理易降解的连接物共价连接的两个独立活性镇痛基团。一种首选实施例包括阿片类药物，如吗啡，通过生理易降解的连接物与来自阿片类或非阿片类化合物组成的群中选择的至少一种镇痛化合物共价连接。适当的共价连接物通过一个或多个内源的内酯、内酰胺或磺酰胺连接而与这两个独立活性的镇痛化合物共价结合。适当的连接物包括内源的羧酸酯、酰胺和磺酰胺基团，以及形成上述内酯、内酰胺或磺酰胺连接的外源基团。
• Controlled-release compositions containing opioid agonist and antagonist
  申请人：——

  公开号：US20020010127A1

  公开（公告）日：2002-01-24

  Controlled-release dosage forms containing an opioid agonist; an opioid antagonist; and a controlled release material release during a dosing interval an analgesic or sub-analgesic amount of the opioid agonist along with an amount of said opioid antagonist effective to attenuate a side effect of said opioid agonist. The dosage form provides analgesia for at least about 8 hours when administered to human patients. In other embodiments, the dose of antagonist released during the dosing interval enhances the analgesic potency of the opioid agonist.

  含有阿片激动剂、阿片拮抗剂和受控释放材料的控释剂型，其在给药间隔期间释放阿片激动剂的镇痛或亚镇痛量以及足以减轻所述阿片激动剂的副作用的阿片拮抗剂的量。当给予人类患者时，该剂型提供至少约8小时的镇痛作用。在其他实施例中，给药间隔期释放的拮抗剂剂量增强了阿片激动剂的镇痛效力。

表征谱图