卡西酮 | 5265-18-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 卡西酮
• 英文名称: (+/-)-cathinone
• 英文别名: α-Amino-propiophenon；α-Methyl-phenacylamin；2-amino-1-phenylpropan-1-one；(±)-cathinone；2-Aminopropiophenone
• CAS: 5265-18-9
• 化学式: C₉H₁₁NO
• 分子量: 149.192
• InChiKey: PUAQLLVFLMYYJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

卡西酮通过酮还原代谢成去甲麻黄碱和伪麻黄碱，比例大约为9:1。高达52%的口服剂量的卡西酮异构体在24小时尿样中以氨基酸醇代谢物的形式被回收。卡西酮也主要在尿液中排出：6小时内口服剂量的40%，24小时内达到84.6%。

Cathinone is metabolized by keto-reduction to norephedrine and norpseudoephedrine at an approximate ratio of 9:1. ... Up to 52% of oral doses of cathinone isomers are recovered in 24 hour urine samples as aminoalcohol metabolites. Cathine is also primarily excreted in the urine: 40% of an oral dose within 6 hours and 84.6% within 24 hours.

来源:Hazardous Substances Data Bank (HSDB)

代谢

口服合成的卡西酮（异构体、外消旋混合物）后，24小时内尿液中回收率为22-52%，主要以氨基酸醇代谢物形式存在。通过气相色谱/质谱（GC/MS）、高效液相色谱（HPLC）和圆二色性（CD）分析，确定了S-(-)-卡西酮的主要代谢物为R/S-(-)-去甲麻黄碱，而R-(+)-卡西酮的主要代谢物为R/R-(-)-去甲伪麻黄碱。这两种氨基酸醇都是由立体特异性酮还原形成的。

... After oral administration of synthesized cathinone (isomers, racemate), 22-52% was recovered in 24 hr urine samples mainly as aminoalcohol metabolites. With GC/MS, HPLC and CD, the main metabolite of S-(-)-cathinone was identified as R/S-(-)-norephedrine and the main metabolite of R-(+)-cathinone as R/R-(-)-norpseudoephedrine. Both aminoalcohols are formed by a stereospecific keto reduction.

来源:Hazardous Substances Data Bank (HSDB)

代谢

Cathinone在肝脏的一级代谢会导致去甲麻黄碱的形成。

First-pass metabolism of cathinone in the liver leads to the formation of norephedrine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

药物辨别范式被用来评估同时给予咖啡因和尼可刹米对低剂量卡西酮辨别的影响。在训练大鼠在双杠杆食物动机操作任务中辨别0.8 mg/kg l-卡西酮和其载体的实验中，0.2 mg/kg卡西酮产生了29.2%的动物选择卡西酮相应杠杆的反应。在分别给予25 mg/kg尼可刹米和20 mg/kg咖啡因的情况下，选择该杠杆的试验比例分别为0%和50%。同时给予咖啡因、尼可刹米或咖啡因加尼可刹米与低剂量卡西酮，产生了强烈的类似卡西酮的辨别表现。这种咖啡因和尼可刹米增强卡西酮的效果反映了含有类似组合的非受控滥用药物，特别是含有这三种成分的减肥药X-112，这种药物在欧洲被广泛滥用。

The drug discrimination paradigm was employed to evaluate the effect of coadministration of both caffeine and nikethamide upon the discrimination of a low dose of cathinone. In rats trained to discriminate between 0.8 mg/kg l-cathinone and its vehicle in a two-lever food-motivated operant task, 0.2 mg/kg cathinone produced 29.2% of responses on the cathinone-appropriate lever. This lever was chosen in 0 and 50% of trials with 25 mg/kg nikethamide and 20 mg/kg caffeine, respectively. Coadministration of caffeine, nikethamide, or caffeine plus nikethamide with low-dose cathinone produced strong cathinone-like discriminative performance. This potentiattion of cathinone by caffeine and nikethamide is reflective of noncontrolled drugs of abuse containing similar combinations especially for that of antiadipositum X-112, a drug containing all three agents and widely abused in Europe.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

研究了(-)-卡西酮、咖啡因及其组合对雄性大鼠性行为的影响。在没有雌性大鼠的情况下，通过记录勃起反应（生殖器清洁、打哈欠/伸展和同性攀爬）来评估雄性大鼠的性行为。通过将雄性与注射了苯甲酸雌二醇和黄体酮的接受性雌性大鼠放在一起来观察交配行为。记录了雄性大鼠的交配模式（攀爬、插入、射精和不应期）。口服卡西酮（5 mg/kg/天）、咖啡因（50 mg/kg/天）及其组合15天的治疗增加了雄性大鼠的性唤起（动机），表现为攀爬表现和会阴探究行为的增加。然而，本研究中测量的勃起和射精反应没有显示出刺激作用。从目前的结果可以推测，卡西酮（阿拉伯茶中的精神刺激成分）改变了雄性模式行为，而咖啡因在同时给药时也改变了卡西酮的效果。然而，我们的数据没有证据表明卡西酮可以被认为是春药。

The effect of (-)-cathinone, caffeine and their combinations was studied on the sexual behavior of male rats. Male sexual activities were assessed by recording the erectile responses (grooming of genitalis, yawning/stretching and homosexual mounting), in the absence of females. The copulatory behavior was observed by caging males with receptive females brought into oestrus with s.c. injection of estradiol benzoate and progesterone. The copulatory pattern of male rats (mounting, intromissions, ejaculations and refractory period) was recorded. The oral treatment of cathinone (5 mg/kg day), caffeine (50 mg/kg day) and their combinations for 15 days increased arousal (motivation) in male rats as evidenced by increased mounting performance and anogenital investigatory behavior. However, erectile and ejaculatory responses, measured in the present study, showed no stimulant effect. It is conceivable from the present results that cathinone, the psychostimulant constituent of khat modified masculine pattern behavior and caffeine also changed the effect of cathinone when administered concomitantly. However, our data provide no evidence that cathinone could be considered as an aphrodisiac.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

治疗恰特草摄入主要是对症治疗。有症状的患者应置于监测之下，进行心电图检查，并频繁监测生命体征。大多数症状在4到6小时内解决。对于持续生命体征异常、有终末器官缺血证据或精神症状的患者，应入院观察。/恰特草/

Treatment of khat ingestion is largely symptomatic. Symptomatic patients should be placed on a monitor, have an ECG obtained, and have vital signs monitored frequently. Most symptoms resolve in 4 to 6 hours. Patients with persistent vital sign abnormalities, evidence of end-organ ischemia, or psychiatric symptoms should be admitted for observations. /Khat/

来源:Hazardous Substances Data Bank (HSDB)

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，辅助通气。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……。预防癫痫发作，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

咀嚼卡特叶时，卡特的活性成分通过口腔吸收。卡西酮、卡因和norephedrine的血浆浓度峰值分别在127分钟、183分钟和200分钟达到。

The active components of khat are absorbed orally by chewing the leaves. The peak plasma concentration of cathinone, cathine, and norephedrine are reached in 127 minutes, 183 minutes, and 200 minutes, respectively.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

四名志愿者咀嚼相当于一次典型咀嚼可乐叶活动四分之一的可乐叶。收集了长达80小时的血液样本，并使用气相色谱-质谱法对生物碱进行了分析。使用计算机化的药物动力学房室分析评估了数据。生物碱的血浆浓度-时间数据可以使用具有两段吸收的两个房室模型来描述。口腔粘膜被认为是第一个吸收段，其中大部分生物碱被吸收（对于卡西酮和卡西尼分别平均+/-标准差为59 +/- 21%和84 +/- 6%）。通过咀嚼从叶子中提取生物碱的效率非常高，只有9.1 +/- 4.2%作为残留物保留。卡西酮从中央房室中以平均半衰期为1.5 +/- 0.8小时被消除。卡西尼的半衰期为5.2 +/- 3.4小时。卡西酮代谢为去甲麻黄碱对其血浆浓度剖面产生了重大影响。咀嚼可乐叶基本上不影响精神物理功能。

Four volunteers chewed khat leaves in an amount equivalent to one-quarter of that used in a typical khat session. Blood samples were collected up to 80 hr and the alkaloids were assayed using gas chromatography-mass spectrometry. The data were evaluated using computerized pharmacokinetic compartmental analysis. The plasma concentration-time data for the alkaloids could be described using a two-compartment model with two-segment absorption. The mucosa of the oral cavity is considered to be the first absorption segment, where the major proportion of the alkaloids is absorbed (mean +/- SD 59 +/- 21% for cathinone and 84 +/- 6% for cathine). The extraction of the alkaloids from the leaves by chewing was very effective with only 9.1 +/- 4.2% remaining as a residue. Cathinone was eliminated from the central compartment with a mean half-life of 1.5 +/- 0.8 hr. The half-life of cathine was 5.2 +/- 3.4 hr. The metabolism of cathinone to norephedrine had a substantial influence on its plasma concentration profile. Psychophysical functions were essentially unaffected by the chewing of khat.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

卡西酮在血浆中的峰值浓度在开始咀嚼后1.5到3.5小时获得。咀嚼60克新鲜阿拉伯茶一小时后，平均血浆浓度可能达到100纳克/毫升。八小时后，血液中几乎检测不到卡西酮。... 只有2%的卡西酮以原形从尿液中排出。

Peak plasma levels of cathinone are obtained 1.5 to 3.5 hours after the onset of chewing. The mean plasma level may reach 100 ng/mL after chewing 60 g fresh khat for one hour. Cathinone is barely detectable in blood after eight hours. ... Only 2 % of cathinone is excreted unchanged in the urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一小部分卡西酮由肾脏原样排泄（0.6%到3.3%）。

A small amount of cathinone is excreted by thekidney unchanged (0.6% to 3.3%).

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  卡西酮 在 盐酸 、 甲醇 、 氢氧化钾 、 sodium amalgam 作用下， 生成 (+)N-methyl-ephedrine methiodide
  参考文献：
  名称：

  Schmidt, Chemisches Zentralblatt, 1911, vol. 82, # II, p. 33

  摘要：

  DOI：
• 作为产物：
  描述：

  (R)-1-羟基-1-苯基丙酮 在 盐酸 、 氨 、 异丙醇 作用下， 生成 卡西酮
  参考文献：
  名称：

  Kirchner, Justus Liebigs Annalen der Chemie, 1959, vol. 628, p. 92,95

  摘要：

  DOI：

文献信息

• Azirines. III. The Preparation of Azirine Derivatives by the Base-Catalyzed Rearrangement of Quaternary Hydrazones
  作者：Shimao Sato

  DOI：10.1246/bcsj.41.1440

  日期：1968.6

  An attempt to prepare azirines by the base-catalyzed rearrangement of some quaternary hydrazones gave the corresponding azirine derivatives. Namely, 2-phenyl-3-methylazirine was obtained by the treatment of propiophenone dimethylhydrazone methiodide with potassium t-butoxide, but treatment with sodium isopropoxide gave 2,5-diphenyl-3,6-dimethylpyrazine or 2-phenyl-2-isopropoxy-3-methylaziridine, depending

  通过碱催化重排一些季腙来制备氮丙啶的尝试得到了相应的氮丙啶衍生物。即，通过用叔丁醇钾处理苯丙酮二甲腙甲硫醚得到 2-苯基-3-甲基氮丙啶，但用异丙醇钠处理得到 2,5-二苯基-3,6-二甲基吡嗪或 2-苯基-2-异丙氧基- 3-甲基氮丙啶，取决于反应条件。通过用异丙醇钠处理环己基苯基酮二甲基腙甲硫醚，以良好的收率获得了2-苯基-3,3-五亚甲基氮丙啶。
• Tandem synthesis of aromatic amides from styrenes in water
  作者：Pratima A. Sathe、Aniket S. Karpe、Aniket A. Parab、Babasao S. Parade、Kamlesh S. Vadagaonkar、Atul C. Chaskar

  DOI：10.1016/j.tetlet.2018.06.021

  日期：2018.7

  one-pot synthesis of aromatic amides has been reported from styrenes in the presence of N-bromosuccinimide and iodine by using aqueous ammonia in water. The reaction proceeds through the formation of α-bromoketone as an intermediate in the presence of NBS and water. α-Bromoketone on reaction with iodine forms bromodiiodoketone which on nucleophilic substitution with aqueous ammonia gives aromatic amide. Substituted

  据报道，在N-溴琥珀酰亚胺和碘的存在下，通过在水中使用氨水，苯乙烯可以方便地一锅合成芳族酰胺。该反应通过在NBS和水的存在下形成中间体α-溴酮来进行。与碘反应时，α-溴酮形成溴二碘酮，在被氨水亲核取代后会生成芳香酰胺。以高收率获得具有宽官能团相容性的取代的芳族酰胺。
• Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase
  作者：Garrett Hellinghausen、Diego A. Lopez、Jauh T. Lee、Yadi Wang、Choyce A. Weatherly、Abiud E. Portillo、Alain Berthod、Daniel W. Armstrong

  DOI：10.1002/chir.22985

  日期：2018.9

  macrocyclic glycopeptide‐based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide‐based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide‐based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary

  通过对万古霉素的Edman降解制备的修饰的基于大环糖肽的手性固定相（CSP）被首次评估为手性选择剂。将其适用性与其他基于大环糖肽的CSP（TeicoShell和VancoShell）进行了比较。此外，还进一步检查了另一种基于大环糖肽的修饰CSP NicoShell。最初的评估集中在与这些糖肽的互补行为上。根据以前的工作，使用了一种筛选方法，用于对50种手性化合物的对映体分离，其中包括氨基酸，农药，兴奋剂和多种药物。使用表面多孔（核-壳）颗粒载体可实现快速有效的手性分离。总体，万古霉素埃德曼降解产物（EDP）与TeicoShell类似，在极性离子模式下对酸性化合物具有高对映选择性。使用液相色谱-质谱联用EDP同时分离5种外消旋脯氨酸的对映异构体，时间约为3分钟。其他亮点包括同时用VancoShell液相色谱分离rac-amphetamine和rac-methamphetamine，用Nico
• Flexible Stereoselective Functionalizations of Ketones through Umpolung with Hypervalent Iodine Reagents
  作者：Pushpak Mizar、Thomas Wirth

  DOI：10.1002/anie.201400405

  日期：2014.6.2

  The functionalization of carbonyl compounds in the α‐position has gathered much attention as a synthetic route because of the wide biological importance of such products. Through polarity reversal, or “umpolung”, we show here that typical nucleophiles, such as oxygen, nitrogen, and even carbon nucleophiles, can be used for addition reactions after tethering them to enol ethers. Our findings allow novel

  由于此类产品具有广泛的生物学重要性，因此羰基化合物在α位上的功能化作为合成途径已引起广泛关注。通过极性反转或“极性”，我们在这里表明典型的亲核试剂，例如氧，氮，甚至碳亲核试剂，在将它们束缚到烯醇醚后，可以用于加成反应。我们的发现可以进行新颖的逆合成规划，并可以快速组装以前只能通过多步序列访问的结构。
• 一种盐酸安非拉酮药物中间体2-二乙氨基-1-苯基丙酮的合成方法
  申请人：成都切斯特科技有限公司

  公开号：CN105461577A

  公开（公告）日：2016-04-06

  一种盐酸安非拉酮药物中间体2-二乙氨基-1-苯基丙酮的合成方法，包括如下步骤：在安装有搅拌器、温度计、回流冷凝器、滴液漏斗的反应容器中，加入α-胺苯丙酮0.23mol,缓慢加入二乙胺0.51-0.53mol,升高溶液温度至85-90℃，反应60-90min,降低溶液温度至60-65℃，加入甲苯120ml,控制搅拌速度130-150rpm,搅拌60-80min,过滤，滤液用草酸溶液洗涤，合并提取液，加入亚硫酸钾溶液，调节pH为8-9，用硝基甲烷提取5-7次，降低溶液温度至5-9℃，析出晶体，过滤，盐溶液洗涤，乙腈洗涤，在环己烷中重结晶，得晶体2-二乙氨基-1-苯基丙酮。