1,3-二甲基戊胺 | 105-41-9

• 物质功能分类: 有机原料 - 氨基化合物
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 1,3-二甲基戊胺
• 中文别名: 2-氨基-4-甲基-正己胺；2-氨基-4-甲基已烷盐酸盐；2-氨基-4-甲基己烷
• 英文名称: 1,3-dimethylamylamine
• 英文别名: 1,3-dimethylpentylamine；DMAA；Methylhexaneamine；4-methylhexan-2-amine
• CAS: 105-41-9
• 化学式: C₇H₁₇N
• mdl: MFCD00025613
• 分子量: 115.219
• InChiKey: YAHRDLICUYEDAU-UHFFFAOYSA-N

物化性质

• 熔点：
  -19°C (estimate)
• 沸点：
  bp760 130-135°
• 密度：
  0.7620-0.7655
• 闪点：
  43℃
• 颜色/状态：
  Liquid
• 气味：
  Amine odor
• 溶解度：
  In water, 1.5X10+4 mg/L at 25 °C (est)
• 蒸汽压力：
  8.9 mm Hg at 25 °C (est)
• 折光率：
  Index of Refraction: 1.4150 at 25 °C
• 保留指数：
  1152.3

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

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。观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预期癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，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)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最小流量/。如果出现低血容量的迹象，使用0.9%的生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人类暴露研究/咖啡因和1,3-二甲基氨基戊烷（DMAA）被广泛单独使用，也常常与膳食补充剂结合使用。目前还没有研究确定在同一研究设计中，单独或联合长期摄入咖啡因或DMAA的安全性。共有50名年轻健康的男性完成了为期12周的每日补充，分别服用安慰剂（n = 11），每天250毫克咖啡因（n = 14），每天50毫克DMAA（n = 13），或每天250毫克咖啡因+每天50毫克DMAA（n = 12）。在补充前和补充6周和12周后，测量了以下变量：体重/组成，静息呼吸率，血压，12导联心电图，尿检，全血计数，代谢面板，血脂面板，以及氧化应激、炎症和心脏生物标志物。任何变量的交互作用均无统计学意义（p > 0.05），四种条件下受试者的变量随时间的变化均很小。除了尿pH值（p = 0.05；Pre (6.5 +/- 0.1)高于第6周 (6.1 +/- 0.1)）和血液CO2（p = 0.02；第12周 (25.9 +/- 0.3 mmol/L)高于第6周 (24.8 +/- 0.3 mmol/L)）外，没有观察到任何其他变量的时间效应（p > 0.05）。这些数据表明，为期12周的每日补充咖啡因和DMAA，无论是单独使用还是联合使用，都不会导致任何测量结果变量出现统计学上的显著变化。

/HUMAN EXPOSURE STUDIES/ Caffeine and 1,3-dimethylamylamine (DMAA) are widely used alone and in combination with dietary supplements. No investigation has determined the safety profile of chronic intake of caffeine or DMAA, alone or in combination, within the same study design. A total of 50 young and healthy men completed 12 weeks of daily supplementation with either a placebo (n = 11), caffeine at 250 mg/day (n = 14), DMAA at 50 mg/day (n = 13), or caffeine at 250 mg/day + DMAA at 50 mg/day (n = 12). Before and after 6 and 12 weeks of supplementation, the following variables were measured: body mass/composition, resting respiratory rate, blood pressure, 12-lead electrocardiogram, urinalysis, complete blood count, metabolic panel, lipid panel, and oxidative stress, inflammatory, and cardiac biomarkers. No interaction effects were noted for any variable (p > 0.05), with little change occurring across time for subjects in any of the four conditions. With the exception of urinary pH (p = 0.05; Pre (6.5 +/- 0.1) higher than week 6 (6.1 +/- 0.1)) and blood CO2 (p = 0.02; week 12 (25.9 +/- 0.3 mmol/L) higher than week 6 (24.8 +/- 0.3 mmol/L)), no time effect was noted for any other variable (p > 0.05). These data indicate that 12 weeks of daily supplementation with caffeine and DMAA, alone or in combination, does not result in a statistically significant change in any of the measured outcome variables.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/人体暴露研究/ 1,3-二甲基丁胺是膳食补充剂中常用的成分。我们之前关于这种物质的研究表明，口服单一剂量后，血压（尤其是收缩压）会出现短暂的升高，但长期摄入后静息血压没有显著增加。此外，涉及使用含有1,3-二甲基丁胺的成品进行两周和八周治疗的干预研究显示，血液中的健康指标几乎没有变化或没有变化。本研究旨在通过一个10周的干预试验来扩展这些发现，以确定男性样本中选定健康指标的变化。 方法：25名健康男性被随机分配到安慰剂组（n = 13）或含有1,3-二甲基丁胺的补充剂组（n = 12），持续10周。在干预前后，测量静息血压和心率，并收集血液样本以确定全血计数、代谢面板和血脂面板。 结果：两组之间血压差异无统计学意义（P > 0.05），尽管补充剂组的收缩压增加了大约6毫米汞柱（舒张压降低了大约4毫米汞柱）。心率随时间变化的主效应显著（P = 0.016），干预前后的值有所下降。从干预前到干预后，肌酐（P = 0.043）显著增加，碱性磷酸酶（P = 0.009）显著减少，两组间差异无统计学意义（P > 0.05）。低密度脂蛋白胆固醇（LDL-C）存在显著交互作用（P = 0.043），补充剂组的值从干预前到干预后下降了大约7毫克/分升（P = 0.034）。血液变量没有其他显著影响。 结论：这些数据表明，含有1,3-二甲基丁胺的膳食补充剂不会导致静息心率或血压的统计学显著增加（尽管使用补充剂时收缩压大约增加了6毫米汞柱）。该补充剂不会对血液中的健康指标产生负面影响。需要进一步的研究，涉及更长的干预期、更大的样本量以及健康和安全的其他测量指标。

/HUMAN EXPOSURE STUDIES/ 1,3-dimethylamylamine is a commonly used ingredient within dietary supplements. Our prior work with this agent indicates a transient increase in blood pressure (systolic in particular) following oral ingestion of a single dosage, but no significant increase in resting blood pressure following chronic ingestion. Moreover, intervention studies involving both two and eight weeks of treatment with finished products containing 1,3-dimethylamylamine indicate minimal or no change in bloodborne markers of health. The present study sought to extend these findings by using a 10-week intervention trial to determine the change in selected markers of health in a sample of men. Methods: 25 healthy men were randomly assigned to either a placebo (n = 13) or to a supplement containing 1,3-dimethylamylamine (n = 12) for a period of 10 weeks. Before and after the intervention, resting blood pressure and heart rate were measured, and blood samples were collected for determination of complete blood count, metabolic panel, and lipid panel. Results: No significant differences were noted between conditions for blood pressure (P > 0.05), although systolic blood pressure increased approximately 6 mmHg with the supplement (diastolic blood pressure decreased approximately 4 mmHg). A main effect for time was noted for heart rate (P = 0.016), with values decreasing from pre to post intervention. There were significant main effects for time for creatinine (increased from pre to post intervention; P = 0.043) and alkaline phosphatase (decreased from pre to post intervention; P = 0.009), with no condition differences noted (P > 0.05). There was a significant interaction noted for low density lipoprotein cholesterol (LDL-C) (P = 0.043), with values decreasing in the supplement group from pre to post intervention approximately 7 mg/ dL (P = 0.034). No other effects of significance were noted for bloodborne variables. Conclusion: These data indicate that a dietary supplement containing 1,3-dimethylamylamine does not result in a statistically significant increase in resting heart rate or blood pressure (although systolic blood pressure is increased approx. 6 mmHg with supplement use). The supplement does not negatively impact bloodborne markers of health. Further study is needed involving a longer intervention period, a larger sample size, and additional measures of health and safety.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

1,3-二甲基戊胺（DMAA）一直是膳食补充剂的一个组成部分，也常用于“派对药片”中，通常与酒精和其他药物联合使用。高于推荐剂量的摄入会导致不良反应，包括脑出血。据我们所知，还没有研究来确定DMAA的药代动力学特征和生理反应。八名男性在隔夜禁食后早上来到实验室，接受了单次25毫克DMAA口服剂量。在DMAA摄入前和摄入后24小时内采集了血液样本，并使用高效液相色谱-质谱法分析了血浆中DMAA的浓度。还测量了静息心率、血压和体温。由于DMAA水平异常，一名受试者被排除在数据分析之外。对剩余七名参与者的分析显示，DMAA的口服清除率为20.02+/- 5 L/hr，口服分布体积为236+/- 38 L，终末半衰期为8.45+/- 1.9小时。潜伏期，即 extravascular 管理后DMAA在循环中出现的延迟，在受试者之间有所不同，但平均大约为8分钟（0.14+/- 0.13小时）。所有受试者的DMAA浓度峰值在摄入后3-5小时内观察到，并且在不同受试者之间非常相似，平均值为~70 ng/mL。心率、血压和体温在很大程度上未受到DMAA治疗的影响。这些数据是首次描述DMAA口服药代动力学特征的。这些发现表明，在DMAA浓度峰值方面，受试者之间存在一致的增加模式，峰值值大约比与DMAA摄入相关的不良事件案例研究中报告的值低15-30倍。最后，单次25毫克剂量的DMAA对静息心率、血压或体温没有明显影响。

1,3-dimethylamylamine (DMAA) has been a component of dietary supplements and is also used within "party pills," often in conjunction with alcohol and other drugs. Ingestion of higher than recommended doses results in untoward effects including cerebral hemorrhage. To our knowledge, no studies have been conducted to determine both the pharmacokinetic profile and physiologic responses of DMAA. Eight men reported to the lab in the morning following an overnight fast and received a single 25 mg oral dose of DMAA. Blood samples were collected before and through 24 hours post-DMAA ingestion and analyzed for plasma DMAA concentration using high-performance liquid chromatography-mass spectrometry. Resting heart rate, blood pressure, and body temperature was also measured. One subject was excluded from the data analysis due to abnormal DMAA levels. Analysis of the remaining seven participants showed DMAA had an oral clearance of 20.02+/- 5 L/hr, an oral volume of distribution of 236+/- 38 L, and terminal half-life of 8.45+/- 1.9 hr. Lag time, the delay in appearance of DMAA in the circulation following extravascular administration, varied among participants but averaged approximately 8 minutes (0.14+/- 0.13 hr). The peak DMAA concentration for all subjects was observed within 3-5 hours following ingestion and was very similar across subjects, with a mean of ~70 ng/mL. Heart rate, blood pressure, and body temperature were largely unaffected by DMAA treatment. These are the first data to characterize the oral pharmacokinetic profile of DMAA. These findings indicate a consistent pattern of increase across subjects with regards to peak DMAA concentration, with peak values approximately 15-30 times lower than those reported in case studies linking DMAA intake with adverse events. Finally, a single 25 mg dose of DMAA does not meaningfully impact resting heart rate, blood pressure, or body temperature.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36/37,S37/39
• 危险类别码：
  R22,R10,R36/37/38,R34
• WGK Germany：
  3
• 危险品运输编号：
  UN 2734PSN1 3（8） / PGII
• 海关编码：
  2921199090

制备方法与用途

用途

1,3-二甲基戊胺广泛用作医药中间体、精细有机合成原料以及催化剂，同时也应用于保健品领域。

反应信息

• 作为反应物：
  描述：

  1,3-二甲基戊胺 在 4-二甲氨基吡啶 、 双(三甲基硅烷基)氨基钾 、 三乙胺 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 18.25h， 生成 C₁₄H₂₄N₂O₂S
  参考文献：
  名称：

  以氮为中心的自由基前体实现的 δ-C–H 卤化反应

  摘要：

  以氮为中心的自由基是多功能的合成中间体，能够进行多种反应，例如氢原子转移 (HAT)、β-断裂和跨不饱和系统的加成。这些中间体在合成中更广泛采用的一个长期障碍是它们的生成困难。在此，我们公开了一种新的氮中心自由基的腙基羧酸前体，及其在通过 1,5-HAT 磺酰基保护的烷基胺的远程 C-H 氟化和氯化反应中的应用。

  DOI：

  10.1021/acs.orglett.2c01261
• 作为产物：
  描述：

  4-甲基-2-己酮 生成 1,3-二甲基戊胺
  参考文献：
  名称：

  Rohrmann; Shonle, Journal of the American Chemical Society, 1944, vol. 66, p. 1517,1519

  摘要：

  DOI：
• 作为试剂：
  描述：

  苯并-15-冠醚-5 在 1,1'-双(二苯基膦)二茂铁 、 tris-(dibenzylideneacetone)dipalladium(0) 、 N-溴代丁二酰亚胺(NBS) 、 1,3-二甲基戊胺 作用下， 以 氯仿 为溶剂， 反应 6.5h， 生成 1,2-dicyanobenzo-4,5-(15-crown-5)
  参考文献：
  名称：

  Design of UV-Vis-NIR panchromatic crown-phthalocyanines with controllable aggregation

  摘要：

  设计并合成了一系列新型供体-受体酞菁化合物，其中含有15-冠-5-氧蒽基团，以扩展光吸收范围，用于进一步的光电应用。

  DOI：

  10.1039/c4dt02759k

文献信息

• Hydroxylated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014733A1

  公开（公告）日：2007-01-18

  Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  羟基化奈必洛尔代谢物在急性给药后以浓度依赖性方式增加人内皮细胞制剂的一氧化氮释放。此外，羟基化奈必洛尔代谢物，包括但不限于4-羟基-6,6'-二氟代-、4-羟基-5-苯酚-6,6'-二氟代-和4-羟基-8-苯并-6,6'-二氟代-，在慢性给药后能够增加人内皮细胞的一氧化氮释放能力。本发明提供了羟基化奈必洛尔代谢物和包含奈必洛尔和/或至少一种羟基化奈必洛尔代谢物和/或至少一种用于治疗心血管疾病的附加化合物的组合物，以及可药用的盐。此外，本发明还提供了通过给药至少一种能够释放治疗有效量的一氧化氮到受血管疾病影响的靶向部位的羟基化奈必洛尔代谢物来治疗和/或预防血管疾病的方法。本发明还涉及通过给药至少一种羟基化奈必洛尔代谢物来治疗和/或预防偏头痛。本发明还可以与治疗代谢综合征障碍的其他治疗联合使用，或作为单一治疗。
• Nitric Oxide Releasing Prodrugs of Therapeutic Agents
  申请人：SATYAM Apparao

  公开号：US20110263526A1

  公开（公告）日：2011-10-27

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其在此处表示为式(I)的化合物，其中药物或治疗剂包含一个或多个功能基团，独立地选自羧酸、氨基、羟基和巯基。该发明还涉及制备一氧化氮释放前药（式(I)的化合物）的方法，含有它们的药物组合物以及使用这些前药的方法。
• 1,2,4-benzothiadiazine derivatives, their preparation and use
  申请人：Novo Nordisk AIS

  公开号：US06242443B1

  公开（公告）日：2001-06-05

  1,2,4-Benzothiadiazine derivatives represented by formula wherein D, R1, R2, R3, R4, R5, R12, R13, R14, R15 are defined in the description, composition thereof and methods for preparing the compounds are described. The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system.

  1,2,4-苯并噻二嗪衍生物的化学式如下： 其中D，R1，R2，R3，R4，R5，R12，R13，R14，R15在描述中有定义，描述了其组成以及制备该化合物的方法。 这些化合物在治疗中枢神经系统、心血管系统、呼吸系统、消化系统和内分泌系统疾病方面具有用途。
• Sulfonamide-Directed Chemo- and Site-Selective Oxidative Halogenation/Amination Using Halogenating Reagents Generated in Situ from Cyclic Diacyl Peroxides
  作者：Denghu Chang、Rong Zhao、Congyin Wei、Yuan Yao、Yang Liu、Lei Shi

  DOI：10.1021/acs.joc.8b00243

  日期：2018.3.16

  The combination of cyclic diacyl peroxides with commercially available halide salts as a unique halogenating system is utilized in Hofmann–Löffler–Freytag-type reaction. This strategy allows for the formation of N-chloroamides, δ-brominated products, and even biologically relevant pyrrolidines under mild conditions in moderate to excellent yields. Meanwhile, the preliminary structure of the in situ

  霍夫曼–勒夫勒–弗雷塔格型反应采用环状二酰基过氧化物与市售卤化物盐的组合作为独特的卤化系统。该策略允许在温和条件下以中等至极好的收率形成N-氯酰胺，δ-溴化产物，甚至生物学上相关的吡咯烷。同时，通过NMR和UV / vis分析研究了原位形成的溴化剂的初步结构。
• Iterative Arylation of Amino Acids and Aliphatic Amines via δ‐C(sp ³ )−H Activation: Experimental and Computational Exploration
  作者：Srimanta Guin、Pravas Dolui、Xinglong Zhang、Satyadip Paul、Vikas Kumar Singh、Sukumar Pradhan、Hediyala B. Chandrashekar、S. S. Anjana、Robert S. Paton、Debabrata Maiti

  DOI：10.1002/anie.201900479

  日期：2019.4.16

  mostly up to the γ‐position. In the present work, we demonstrate the diverse (hetero)arylation of amino acids and analogous aliphatic amines selectively at the remote δ‐position by tuning the reactivity controlled by ligands. An organopalladium δ‐C(sp3)−H activated intermediate has been isolated and crystallographically characterized. Mechanistic investigations carried out experimentally in conjunction

  定向C H功能化已实现为传统方法的补充工具，可直接访问非蛋白原性氨基酸。尽管这样的过程主要限于γ位置。在当前的工作中，我们通过调节配体控制的反应性，证明了在远端δ位选择性地使氨基酸和类似的脂肪族胺具有多种（杂）芳基化作用。已分离出有机钯δ-C（sp 3）-H活化中间体，并进行了晶体学表征。实验研究与计算研究相结合进行的机理研究揭示了取决于基材结构的机理图上的差异。

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