1-丁基-3-(1-萘甲酰基)吲哚 | 208987-48-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 1-丁基-3-(1-萘甲酰基)吲哚
• 英文名称: JWH 073
• 英文别名: (1-butyl-1H-indol-3-yl)-1-naphthalenylmethanone；1-butyl-3-(1-naphthoyl)indole；(1-butylindol-3-yl)-naphthalen-1-ylmethanone
• CAS: 208987-48-8
• 化学式: C₂₃H₂₁NO
• 分子量: 327.426
• InChiKey: VCHHHSMPMLNVGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  1

ADMET

代谢

尿液中的/JWH-018和JWH-073/含量不足或较低，需要对它们的代谢物进行详细鉴定，这些代谢物随尿液排出并在血液中存在。利用气相色谱-质谱和液相色谱-质谱，研究人员在人和大鼠的尿样中鉴定出一系列代谢物，这些代谢物是以下反应的产物：(a) 父化合物与羟基在芳香族和脂肪族残基上的单羟基化和二羟基化，(b) 羧基化，(c) N-脱烷基化，(d) N-脱烷基化和羟基化。在人类中，主要的尿液代谢物是单羟基化形式，而在大鼠中发现了N-脱烷基化和N-脱烷基单羟基化形式。

... The lack or low content of /JWH-018 and JWH-073/ in urine requires detailed identification of their metabolites, which are excreted with urine and are present in blood. Using gas and liquid chromatography-mass spectrometry, /investigators/ identified a series of metabolites in urine samples from humans and rats that were products of the following reactions: (a) mono- and dihydroxylation of the parent compounds with hydroxyl groups located at aromatic and aliphatic residues, (b) carboxylation, (c) N-dealkylation and (d) N-dealkylation and hydroxylation. The prevailing urinary metabolites in humans are monohydroxylated forms, while N-dealkylated and N-dealkyl monohydroxylated forms are found in rats. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

本研究评估了九种人类重组尿苷二磷酸葡萄糖醛酸基转移酶（UGT）同种物以及人类肝脏和肠道微粒体的能力，以葡萄糖醛酸化1-萘基-1-(1-戊基-1H-吲哚-3-基)-甲酮（JWH-018）和(1-丁基-1H-吲哚-3-基)-1-萘基-甲酮（JWH-073）的羟基代谢物，这两种物质是K2产品中最常见的合成大麻素。使用液相色谱/串联质谱识别和表征了结合物，而使用高效液相色谱-紫外可见方法量化了动力学参数。UGT1A1、UGT1A3、UGT1A9、UGT1A10和UGT2B7被证明是主要涉及的酶，对某些羟基化K2显示出相对较高的亲和力，K(m)值在12至18微摩尔之间。这些UGT也显示出对化合物的代谢能力很高，这表明K2代谢物可能被迅速葡萄糖醛酸化并从体内排出。

... This study evaluates nine human recombinant uridine diphosphate-glucuronosyltransferase (UGT) isoforms and human liver and intestinal microsomes for their ability to glucuronidate hydroxylated metabolites of 1-naphthalenyl-1(1-pentyl-1H-indol-3-yl)-methanone (JWH-018) and (1-butyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-073), the two most common synthetic cannabinoids found in K2 products. Conjugates were identified and characterized using liquid chromatography/tandem mass spectrometry, whereas kinetic parameters were quantified using high-performance liquid chromatography-UV-visible methods. UGT1A1, UGT1A3, UGT1A9, UGT1A10, and UGT2B7 were shown to be the major enzymes involved, showing relatively high affinity with K(m) ranging from 12 to 18 uM for some hydroxylated K2s. These UGTs also exhibited a high metabolic capacity for these compounds, which indicates that K2 metabolites may be rapidly glucuronidated and eliminated from the body. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

两个主要摄入JWH-018的对象排泄出了5-(3-(1-萘甲酰)-1H-吲哚-1-基)-戊酸（>30 ng/mL）和(1-(5-羟基戊基)-1H-吲哚-3-基)(萘-1-基)-甲酮（>50 ng/mL）的葡萄糖苷酸结合物。有趣的是，在这些标本中检测到了JWH-018和JWH-073的氧化代谢物，这表明JWH-018代谢去甲基化为JWH-073，或者是一种未报告的、之前的JWH-073暴露。一个摄入了JWH-018和JWH-073混合物的对象的代谢轮廓与那些可能只摄入JWH-018的对象生成的轮廓相似。JWH-018和JWH-073的氧化代谢物模式相同，但JWH-018的代谢物以较低的浓度被排泄。

... Two subjects that consumed JWH-018 primarily excreted glucuronidated conjugates of 5-(3-(1-naphthoyl)-1H-indol-1-yl)-pentanoic acid (>30 ng/mL) and (1-(5-hydroxypentyl)-1H-indol-3-yl)(naphthalene-1-yl)-methanone (>50 ng/mL). Interestingly, oxidized metabolites of both JWH-018 and JWH-073 were detected in these specimens, suggesting either metabolic demethylation of JWH-018 to JWH-073 or a nonreported, previous JWH-073 exposure. Metabolic profiles generated from a subject who consumed a mixture of JWH-018 and JWH-073 were similar to profiles generated from subjects who presumably consumed JWH-018 exclusively. Oxidized metabolites of JWH-018 and JWH-073 were of the same pattern, but JWH-018 metabolites were excreted at lower concentrations.

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 在个人报告称自行给药JWH-018或JWH-018与JWH-073混合物后收集的四个尿样标本结果显示如下：(1)所有测试的代谢物都以高浓度被排出，(2)(omega)-和(omega-1)-羟基代谢物仅以葡萄糖醛酸苷形式排出，(3)大约5%-80%的(omega)-羧基代谢物以葡萄糖醛酸苷形式排出。...

... Results from four urine specimens collected after individuals reportedly self-administered either JWH-018 or a mixture of JWH-018 and JWH-073 showed the following: (1) all tested metabolites were excreted in high concentrations, (2) (omega)- and (omega-1)-hydroxyl metabolites were exclusively excreted as glucuronic acid conjugates, and (3) approximately 5%-80% of the (omega)-carboxyl metabolites was excreted as glucuronic acid conjugates. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

大多数心理障碍可以通过简单的安慰来处理，可能需要辅助使用劳拉西泮、地西泮或咪达唑仑。窦性心动过速通常不需要治疗，但如果必要，可以使用β-受体阻滞剂进行控制。直立性低血压可以通过低头位和静脉输液来处理。没有特定的解毒剂。/大麻/

Most psychological disturbances may be managed by simple reassurance, possibly with adjunctive use of lorazepam, diazepam, or midazolam. Sinus tachycardia usually does not require treatment but if necessary may be controlled with beta-blockers. Orthostatic hypotension responds to head down position and IV fluids. There is no specific antidote. /Marijuana/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

摄入后进行解毒。院前急救。如果有的话，给予活性炭。医院。给予活性炭。如果可以迅速给予活性炭，则不需要胃排空。增强消除。由于大麻素分布量大，这些程序无效。/大麻/

Decontamination after ingestion. Prehospital. Administer activated charcoal if available. Hospital. Administer activated charcoal. Gastric emptying is not necessary if activated charcoal can be given promptly. Enhanced elimination. These procedures are not effective owing to the large volume of distribution of cannabinoids. /Marijuana/

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。寻求医疗帮助。 /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)

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"，最低流量/。如果出现低血容量的迹象，使用0.9%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)

反应信息

• 作为产物：
  描述：

  吲哚 在 aluminum (III) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 1-丁基-3-(1-萘甲酰基)吲哚
  参考文献：
  名称：

  Synthesis, cytotoxicity and QSAR studies of indolic cannabinoid-triazole hybrids

  摘要：

  DOI：

  10.1016/j.molstruc.2023.135889

文献信息

• [EN] USE OF THE AMINOALKYLINDOLE JWH-073-M4 AND RELATED COMPOUNDS AS NEUTRAL CB1 RECPTOR ANTAGONISTS FOR THE TREATMENT OF ALCOHOLISM, DRUG ABUSE, OBESITY, AND OBESITY-RELATED DISEASES<br/>[FR] UTILISATION DE L'AMINOALKYLINDOLE JWH-073-M4 ET COMPOSÉS APPARENTÉS COMME ANTAGONISTES NEUTRES DES RÉCEPTEURS AUX CANNABINOÏDES DE TYPE 1 POUR LE TRAITEMENT DE L'ALCOOLISME, DE L'ABUS DE DROGUES, DE L'OBÉSITÉ ET DES MALADIES LIÉES À L'OBÉSITÉ
  申请人：UNIV ARKANSAS

  公开号：WO2013106349A1

  公开（公告）日：2013-07-18

  Novel alkylindoles that bind tightly to cannabinoid receptors and are neutral antagonists for the cannabinoid 1 receptor and agonists for the cannabinoid 2 receptor are provided. These compounds are useful for treating alcoholism and drug abuse and for treating obesity.

  提供了一种新型烷基吲哚化合物，它们与大麻素受体结合紧密，是大麻素1受体的中性拮抗剂和大麻素2受体的激动剂。这些化合物对治疗酗酒和药物滥用以及治疗肥胖症是有用的。
• Detection of Synthetic Cannabinoids
  申请人：Benchikh Elouard

  公开号：US20120208213A1

  公开（公告）日：2012-08-16

  The invention describes methods and kits for detecting and determining current and future synthetic cannabinoids from the JWH and CP families. Unique antibodies derived from novel immunogens enable said methods and kits.

  这项发明描述了检测和确定JWH和CP家族当前和未来合成大麻素的方法和试剂盒。源自新型免疫原的独特抗体使这些方法和试剂盒得以实现。
• Detection of synthetic cannabinoids
  申请人：Randox Laboratories Ltd.

  公开号：EP2698385A1

  公开（公告）日：2014-02-19

  The invention describes methods and kits for detecting and determining current and future synthetic cannabinoids from the JWH and CP families. Unique antibodies derived from immunogens enable said methods and kits.

  这项发明描述了检测和确定JWH和CP家族当前和未来合成大麻素的方法和试剂盒。从免疫原获得的独特抗体使这些方法和试剂盒成为可能。
• DETECTION OF SYNTHETIC CANNABINOIDS
  申请人：RANDOX LABORATORIES LIMITED

  公开号：US20150118763A1

  公开（公告）日：2015-04-30

  The invention describes methods and kits for detecting and determining current and future synthetic cannabinoids from the JWH and CP families. Unique antibodies derived from novel immunogens enable said methods and kits.

  这项发明描述了用于检测和确定当前和未来JWH和CP家族合成大麻素的方法和试剂盒。从新型免疫原中获得的独特抗体使这些方法和试剂盒得以实现。
• TEST KIT FOR THE QUANTITATIVE DETERMINATION OF NARCOTIC DRUGS
  申请人：CHIRON AS

  公开号：US20150204893A1

  公开（公告）日：2015-07-23

  A test kit for the quantitative determination of narcotic drugs comprising (A) series of sealed vessels, each vessel containing a deuterium free isotopologue of a narcotic drug in exactly defined concentrations and quantities, wherein the isotopologue differs from vessel to vessel and—wherein the quantities of the isotopologue differ from vessel to vessel or are the same for all vessels; and/or (B) series of sealed vessels, each vessel containing in exactly defined concentrations and quantities the same isotopologue in quantities which differ from vessel to vessel; wherein the free isotopologues are selected from narcotic drugs; prodrugs, salts, solvates, hydrates and polymorphs and contain at least three stable isotopes selected from the group consisting of 13 C, 15 N and 18 O in the molecule with a degree of labeling of at least 95 mol-%; the use of the test kit and a method for quantitatively determining narcotic drugs.

  一种用于定量测定麻醉药物的检测试剂盒，包括（A）一系列密封容器，每个容器中含有一种去氘同位素麻醉药物，其浓度和数量均被精确定义，其中同位素从容器到容器不同，同位素的数量在容器到容器之间不同或对所有容器都相同；和/或（B）一系列密封容器，每个容器中含有相同的同位素，其浓度和数量被精确定义，数量在容器到容器之间不同；其中自由同位素选自麻醉药物、前药、盐、溶剂、水合物和多晶形，并且在分子中至少包含三种稳定同位素，所述稳定同位素选自13C、15N和18O，其标记度至少为95摩尔％；使用该检测试剂盒和一种定量测定麻醉药物的方法。