[1-(5-氟戊基)吲哚-3-基]-(2,2,3,3-四甲基环丙基)甲酮 | 1364933-54-9

• 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-(5-氟戊基)吲哚-3-基]-(2,2,3,3-四甲基环丙基)甲酮
• 英文名称: XLR-11
• 英文别名: (1-(5-fluoropentyl)-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone；[1-(5-fluoropentyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone
• CAS: 1364933-54-9
• 化学式: C₂₁H₂₈FNO
• 分子量: 329.458
• InChiKey: PXLDPUUMIHVLEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

合成大麻素类药物的代谢轮廓知识对于尿检中药物的检测非常重要，因为人类尿液中通常不存在或只含有极少量的母体大麻素。据报道，真菌 Cunninghamella elegans 是一个有用的代谢研究工具，因此本研究对其应用于合成大麻素代谢的适用性进行了考察。在本研究中，8-喹啉基-1-(5-氟戊基)-1H-吲哚-3-羧酸酯（5F-PB-22）、8-喹啉基-1-戊基-1H-吲哚-3-羧酸酯（PB-22）、[1-(5-氟戊基)-1H-吲哚-3-基](2,2,3,3-四甲基环丙基)甲酮（XLR-11）和(1-戊基-1H-吲哚-3-基)(2,2,3,3-四甲基环丙基)甲酮（UR-144）与 C. elegans 一起孵育，并使用液相色谱-四极飞行时间质谱鉴定代谢物。获得的代谢物与报道的人类代谢物进行了比较，以评估该真菌外推人类代谢的适宜性。5F-PB-22 经历了羟基化、二氢二醇形成、氧化脱氟、氧化脱氟至羧酸、酯水解和葡萄糖苷化，单独或联合进行。PB-22 的代谢物是通过羟基化、二羟基化、三羟基化、二氢二醇形成、酮形成、羧基化、酯水解和葡萄糖苷化产生的，单独或联合进行。XLR-11 通过羟基化、二羟基化、醛形成、羧基化、氧化脱氟、氧化脱氟至羧酸和葡萄糖苷化进行转化，单独或联合进行。UR-144 通过羟基化、二羟基化、三羟基化、醛形成、酮形成、羧基化、N-去烷基化和组合进行代谢。这些发现与以前报道的人类代谢一致，除了观察到的小范围的酯水解和葡萄糖苷化的缺失。尽管有限制，C. elegans 展现了产生包括 XLR-11 和 UR-144 的一些主要人类代谢物在内的广泛代谢物的能力，显示了其对新兴合成大麻素代谢的潜力。

The knowledge of metabolic profile of synthetic cannabinoids is important for the detection of drugs in urinalysis due to the typical absence or low abundance of parent cannabinoids in human urine. The fungus Cunninghamella elegans has been reported to be a useful tool for metabolism study and thus applicability to synthetic cannabinoid metabolism was examined. In this study, 8-quinolinyl 1-(5-fluoropentyl)-1H-indole-3-carboxylate (5F-PB-22), 8-quinolinyl 1-pentyl-1H-indole-3-carboxylate (PB-22), [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11) and (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (UR-144) were incubated with C. elegans and the metabolites were identified using liquid chromatography-quadrupole time-of-flight mass spectrometry. The obtained metabolites were compared with reported human metabolites to assess the suitability of the fungus to extrapolate human metabolism. 5F-PB-22 underwent dihydroxylation, dihydrodiol formation, oxidative defluorination, oxidative defluorination to carboxylic acid, ester hydrolysis and glucosidation, alone and/or in combination. The metabolites of PB-22 were generated by hydroxylation, dihydroxylation, trihydroxylation, dihydrodiol formation, ketone formation, carboxylation, ester hydrolysis and glucosidation, alone and/or in combination. XLR-11 was transformed through hydroxylation, dihydroxylation, aldehyde formation, carboxylation, oxidative defluorination, oxidative defluorination to carboxylic acid and glucosidation, alone and/or in combination. UR-144 was metabolised by hydroxylation, dihydroxylation, trihydroxylation, aldehyde formation, ketone formation, carboxylation, N-dealkylation and combinations. These findings were consistent with previously reported human metabolism except for the small extent of ester hydrolysis observed and the absence of glucuronidation. Despite the limitations, C. elegans demonstrated the capacity to produce a wide variety of metabolites including some major human metabolites of XLR-11 and UR-144 at high abundance, showing the potential for metabolism of newly emerging synthetic cannabinoids.

来源:Hazardous Substances Data Bank (HSDB)

代谢

近年来，合成大麻素在非法药物市场上出现，尤其是在互联网上，导致这些药物的滥用。目前对于参与这些药物代谢的具体酶的了解有限。在本研究中，我们调查了细胞色素P450（CYP）酶在两种合成大麻素（1-戊基-1H-吲哚-3-基）-(2,2,3,3-四甲基环丙基)甲酮（UR-144）和[1-(5-氟戊基)-1H-吲哚-3-基)](2,2,3,3-四甲基环丙基)甲酮（XLR-11）的代谢中的作用。本研究通过识别参与UR-144和XLR-11代谢的特定CYP酶，扩展了以前的研究，利用九种重组酶（CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 3A4, 和 2E1）的面板。接着，研究了针对CYP1A2, 2B6, 2C9, 2C19, 2D6和3A4的特定抑制剂在人肝微粒体（HLM）中的影响。UR-144和XLR-11与重组CYP酶的孵化显示，UR-144和XLR-11在四甲基环丙基（TMCP）部分被CYP3A4广泛代谢，同时CYP1A2和CYP2C19也表现出活性。在HLM中抑制CYP3A4减弱了UR-144和XLR-11的代谢，而抑制HLM中的其他CYP酶只有轻微的影响。因此，CYP3A4是UR-144和XLR-11的CYP介导代谢的主要贡献者，CYP1A2也有较小的贡献。因此，UR-144和XLR-11的使用者可能会受到潜在的药物-药物相互作用的影响，如果他们同时使用CYP3A4诱导剂（例如一些抗癫痫药）或抑制剂（例如一些抗真菌药物）。

In recent years, synthetic cannabinoids have emerged in the illicit drug market, in particular via the Internet, leading to abuse of these drugs. There is currently limited knowledge about the specific enzymes involved in the metabolism of these drugs. In this study, we investigated the cytochrome P450 (CYP) enzymes involved in the metabolism of the two synthetic cannabinoids (1-pentyl-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone (UR-144) and [1-(5-fluoropentyl)-1H-indol-3-yl)](2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11). This study extends previous studies by identifying the specific CYP enzymes involved in the metabolism of UR-144 and XLR-11 utilizing a panel of nine recombinant enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 3A4, and 2E1). This is followed by an investigation of the effect of specific inhibitors targeted against CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A4 in human liver microsomes (HLM). Incubations of UR-144 and XLR-11 with recombinant CYP enzymes revealed that UR-144 and XLR-11 are extensively metabolized by CYP3A4 at the tetramethylcyclopropyl (TMCP) moiety, but also CYP1A2 and CYP2C19 showed activity. Inhibition of CYP3A4 in HLM attenuated the metabolism of UR-144 and XLR-11, while inhibition of the other CYP enzymes in HLM had only minor effects. Thus, CYP3A4 is the major contributor to the CYP mediated metabolism of UR-144 and XLR-11 with minor contributions from CYP1A2. Users of UR-144 and XLR-11 are thus subject to the influence of potential drug-drug interactions, if they are concomitantly medicated with CYP3A4 inducers (e.g. some antiepileptics) or inhibitors (e.g. some antifungal drugs).

来源:Hazardous Substances Data Bank (HSDB)

代谢

自2000年代中期以来，合成大麻素作为消遣性药物被滥用，导致许多国家对这类物质进行了管制。为了规避立法，制造商不断推出新的化合物；1-(5-氟戊基)吲哚-3-基)-(2,2,3,3-四甲基环丙基)甲酮（XLR-11），氟化的UR-144类似物，是最新的和广泛滥用药物之一，其使用现在与急性肾损伤有关。我们的目标是研究XLR-11的代谢，以识别分析方法中的主要尿液靶标，并澄清当一个或多个亲本合成大麻素可能成为来源时，代谢物的来源。我们将10 umol/L的XLR-11与人类肝细胞混合培养，并在1小时和3小时后取样。样品通过高分辨率质谱仪进行TOF扫描，然后进行信息依赖性采集触发的产物离子扫描，动态背景减法和质量缺陷过滤器。扫描被不同的数据处理算法彻底挖掘（Metabolite Pilot 1.5）。XLR-11经历了I相和II相代谢，产生了超过25种代谢物，包括羟基化、羧基化、半缩酮和半缩醛形成、内脱水以及一些氧化代谢物的进一步葡萄糖醛酸化。没有观察到硫酸盐或谷胱甘肽结合。XLR-11也被去氟化，形成UR-144代谢物。基于质谱峰面积，我们确定主要代谢物是2'-羧基-XLR-11、UR-144戊酸、5-羟基-UR-144、羟基-XLR-11葡萄糖醛酸苷和2'-羧基-UR-144戊酸。次要代谢物是上述生物转化的组合，通常是葡萄糖醛酸化的。这些是定义XLR-11代谢主要尿液靶标的首批数据，可以记录XLR-11在法医和临床调查中的摄入情况。

Since the mid-2000s synthetic cannabinoids have been abused as recreational drugs, prompting scheduling of these substances in many countries. To circumvent legislation, manufacturers constantly market new compounds; [1-(5-fluoropentyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11), the fluorinated UR-144 analog, is one of the most recent and widely abused drugs, and its use is now linked with acute kidney injury. Our goal was to investigate XLR-11 metabolism for identification of major urinary targets in analytical methods and to clarify the origin of metabolites when one or more parent synthetic cannabinoids can be the source. We incubated 10 umol/L XLR-11 with pooled human hepatocytes and sampled after 1 and 3 hr. Samples were analyzed by high-resolution mass spectrometry with a TOF scan followed by information-dependent acquisition triggered product ion scans with dynamic background subtraction and mass defect filters. Scans were thoroughly data mined with different data processing algorithms (Metabolite Pilot 1.5). XLR-11 underwent phase I and II metabolism, producing more than 25 metabolites resulting from hydroxylation, carboxylation, hemiketal and hemiacetal formation, internal dehydration, and further glucuronidation of some oxidative metabolites. No sulfate or glutathione conjugation was observed. XLR-11 also was defluorinated, forming UR-144 metabolites. On the basis of mass spectrometry peak areas, we determined that the major metabolites were 2'-carboxy-XLR-11, UR-144 pentanoic acid, 5-hydroxy-UR-144, hydroxy-XLR-11 glucuronides, and 2'-carboxy-UR-144 pentanoic acid. Minor metabolites were combinations of the biotransformations mentioned above, often glucuronidated. These are the first data defining major urinary targets of XLR-11 metabolism that could document XLR-11 intake in forensic and clinical investigations.

来源:Hazardous Substances Data Bank (HSDB)

代谢

(1-(5-氟戊基)-1H-吲哚-3-基)(2,2,3,3-四甲基环丙基)甲酮(XLR-11)，一种新型合成大麻素，的代谢过程使用HepaRG细胞培养进行了研究。将HepaRG细胞与药物共同培养48小时，并通过液-液萃取法从培养介质中提取代谢物。提取物通过液相色谱/质谱分析检测代谢物。在XLR-11的培养介质中鉴定出了N-(5-羟基戊基)代谢物和N-戊酸代谢物，以及几个其他代谢物，推测是由前两个代谢物和XLR-11的氧化形成的。还分析了XLR-11使用者的尿液提取物；然而，尿液中检测到的代谢物与介质中的XLR-11代谢物不同。使用HepaRG细胞对XLR-11的热降解产物，即XLR-11降解物，进行的代谢实验发现，尿液中的代谢物与XLR-11降解物代谢物几乎相同。这些发现表明，当用户吸食含有XLR-11的草药产品时，大部分XLR-11被加热降解。

The metabolism of (1-(5-fluoropentyl)-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11), a novel synthetic cannabinoid, was studied using a HepaRG cell culture. The HepaRG cells were incubated with the drug for 48 hours and the metabolites were extracted from the culture medium by liquid-liquid extraction. The extract was analyzed by liquid chromatography/mass spectrometry to detect the metabolites. N-(5-Hydroxypentyl) metabolite and N-pentanoic acid metabolite were identified in the culture medium of XLR-11, and several other metabolites, presumably formed by oxidation of the first two metabolites and XLR-11, were detected. The extract of an XLR-11 user's urine was also analyzed; however, the metabolites detected in the urine were different from XLR-11 metabolites in the medium. A metabolic experiment with the thermal degradation product of XLR-11, XLR-11 degradant, using HepaRG cells revealed that the urinary metabolites were almost identical to the XLR-11 degradant metabolites. These findings suggest that most of the XLR-11 was degraded by heating when the user smoked the herbal product containing XLR-11.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：XLR-11是一种在美国日益被用作大麻替代品的合成大麻素。人类研究：有报道称使用合成大麻素如XLR-11与急性肾损伤有关。还有至少一例与XLR-11吸入相关的急性脑梗塞。在用人淋巴细胞和口腔及肺来源的人细胞系进行的体外单细胞凝胶电泳（SCGE）试验中发现了明确的剂量依赖效应。XLR-11诱导微核，这是由于染色体畸变形成的。动物研究：在用大鼠和小鼠进行的研究中，XLR-11与delta9-四氢大麻酚（delta9-THC），大麻的精神活性成分，共享大麻素效果，并且被发现与delta9-THC大致等效。XLR-11在大鼠中减少了运动活动，持续多达90分钟。气溶胶化的XLR-11没有在小鼠中产生全部的大麻拟态效应。在细菌（沙门氏菌/微粒体）测试中没有发现诱导基因突变的证据。

IDENTIFICATION AND USE: XLR-11 is a synthetic cannabinoid increasingly used in the United States as a marijuana substitute. HUMAN STUDIES: There have been case reports of acute kidney injury associated with the use of synthetic cannabinoids such as XLR-11. There has also been at least one case of acute cerebral infarction associated with XLR-11 inhalation. Clear dose-dependent effects were found in in vitro single cell gel electrophoresis (SCGE) assays with human lymphocytes and with buccal- and lung-derived human cell lines. XLR-11 induced micronuclei which are formed as a consequence of chromosomal aberrations. ANIMAL STUDIES: In studies using rats and mice, XLR-11 shared cannabinoid effects with delta9-tetrahydrocannabinol (delta9-THC), the psychoactive component of marijuana, and was found to be roughly equipotent with delta9-THC. XLR-11 decreased locomotor activity in rats for up to 90 min. Aerosolized XLR-11 did not produce the full profile of cannabimimetic effects in mice. No evidence for induction of gene mutations was detected in bacterial (Salmonella/microsome) tests.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

立即急救：确保已经进行了充分去污。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、气囊面罩装置或口袋面罩，按训练进行操作。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。如果发生呕吐，让患者向前倾或将其置于左侧（如果可能，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/

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

基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。必要时进行吸痰。观察呼吸不足的迹象，并在需要时辅助通气。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，并在必要时进行治疗……。监测休克，并在必要时进行治疗……。预防癫痫发作，并在必要时进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用0.9%的生理盐水（NS）连续冲洗每只眼睛……。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，并且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。/毒药A和B/

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 ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于失去意识、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。考虑对肺水肿进行药物治疗...。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇（舒喘灵）...。监测心率和必要时治疗心律失常...。开始静脉输注5%葡萄糖水（D5W），保持通路开放，最小流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸钠林格氏液（LR）。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...。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...。/毒物A和B/

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 TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) 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

案例报告/合成大麻是一种已知的非法滥用药物，会导致不良的神经和拟交感神经效应。它们是一种新兴的健康风险：11%的高三学生报告在过去12个月内吸食过它们。我们描述了与合成大麻相关的急性肾损伤毒理综合征的流行病学，回顾了该集群的毒理学和公共卫生调查，并描述了集群调查的临床影响。2012年5月至10月，俄勒冈州和华盛顿西南部发生了9例受毒理综合征影响的病例系列。病例被定义为13-40岁无已知肾脏疾病的人中急性肾损伤（肌酐>1.3 mg/dL），他们报告吸食合成大麻。毒理学实验室使用液相色谱和飞行时间质谱来检测临床和产品样本中的合成大麻、它们的代谢物和已知的肾毒素。公共卫生警报通知了临床医生、执法部门和社区关于该集群的信息，并提醒他们注意与新兴滥用药物相关的毒综合征。患者是15-27岁的男性（中位数18岁），有剧烈恶心和侧腹或腹痛，包括两对兄弟姐妹。肌酐峰值水平为2.6-17.7 mg/dL（中位数6.6 mg/dL）。所有患者都住院了；一人需要透析；没有人死亡。没有发现急性肾损伤或肾毒素的其他原因。患者报告在便利店、烟草店和成人书店轻松购买合成大麻。一个临床样本和两个产品样本含有新型合成大麻成分XLR-11（[1-(5-氟戊基)-1H-吲哚-3-基](2,2,3,3-四甲基环丙基)甲酮）的证据。无论是由直接毒性、遗传倾向还是尚未识别的肾毒素引起，这种合成大麻暴露与急性肾损伤的联系都强化了我们需要警惕检测与新兴滥用药物相关的新的毒理综合征。液相色谱和飞行时间质谱是确定这些不断发展的产品中的活性成分并评估它们是否有毒污染的有用工具。

/CASE REPORTS/ Synthetic cannabinoids are illegal drugs of abuse known to cause adverse neurologic and sympathomimetic effects. They are an emerging health risk: 11% of high school seniors reported smoking them during the previous 12 months. We describe the epidemiology of a toxicologic syndrome of acute kidney injury associated with synthetic cannabinoids, review the toxicologic and public health investigation of the cluster, and describe clinical implications of the cluster investigation. Case series of nine patients affected by the toxicologic syndrome in Oregon and southwestern Washington during May-October 2012. Cases were defined as acute kidney injury (creatinine > 1.3 mg/dL) among persons aged 13-40 years without known renal disease who reported smoking synthetic cannabinoids. Toxicology laboratories used liquid chromatography and time-of-flight mass spectrometry to test clinical and product specimens for synthetic cannabinoids, their metabolites, and known nephrotoxins. Public health alerts informed clinicians, law enforcement, and the community about the cluster and the need to be alert for toxidromes associated with emerging drugs of abuse. Patients were males aged 15-27 years (median, 18 years), with intense nausea and flank or abdominal pain, and included two sets of siblings. Peak creatinine levels were 2.6-17.7 mg/dL (median, 6.6 mg/dL). All patients were hospitalized; one required dialysis; none died. No alternate causes of acute kidney injury or nephrotoxins were identified. Patients reported easily purchasing synthetic cannabinoids at convenience, tobacco, and adult bookstores. One clinical and 2 product samples contained evidence of a novel synthetic cannabinoid, XLR-11 ([1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone). Whether caused by direct toxicity, genetic predisposition, or an as-yet unidentified nephrotoxin, this association between synthetic cannabinoid exposure and acute kidney injury reinforces the need for vigilance to detect new toxicologic syndromes associated with emerging drugs of abuse. Liquid chromatography and time-of-flight mass spectrometry are useful tools in determining the active ingredients in these evolving products and evaluating them for toxic contaminants.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为产物：
  描述：

  2,2,3,3-四甲基环丙烷羧酸酰氯 在 二甲基氯化铝 、 sodium hydride 作用下， 以 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.5h， 生成 [1-(5-氟戊基)吲哚-3-基]-(2,2,3,3-四甲基环丙基)甲酮
  参考文献：
  名称：

  广泛中和合成大麻素疫苗

  摘要：

  合成大麻素 (SC) 是构成主要公共卫生风险的精神活性物质的重要组成部分。由于 SCs 种类繁多，主动免疫产生的广泛中和抗体提供了一种有趣的途径来对抗大麻素使用障碍。在这里，我们探讨了针对两类 SCs 的抗体亲和力和交叉反应性的半抗原设计。在筛选的 10 个半抗原中，3 个疫苗组显示亚微摩尔 IC 50，每个针对我们的 22 种药物中的 5-6 种化合物。此外，当通过电子烟或腹腔注射给药时，SCs 被成功隔离，这在动物模型中通过观察运动、体温和药代动力学得到证实。我们还发现了通过混合疫苗方法同时减弱两种药物类别的协同效应。总的来说，我们的研究为开发针对 SCs 的疫苗提供了全面的基础。

  DOI：

  10.1021/jacsau.0c00057

文献信息

• [EN] 3BETA-(4-METHOXYBENZYLOXY)PREGN-5-EN-20-ONE FOR USE IN THE TREATMENT OF CANNABINOIDS-RELATED DISORDERS<br/>[FR] 3BÊTA-(4-MÉTHOXYBENZYLOXY)PREGN-5-ÉN-20-ONE POUR UNE UTILISATION DANS LE TRAITEMENT DE TROUBLES LIÉS AUX CANNABINOÏDES
  申请人：AELIS FARMA

  公开号：WO2019162328A1

  公开（公告）日：2019-08-29

  The present invention generally relates to a specific pregnenolone derivative for its use for the treatment of a Cannabinoids-Related Disorder. More particularly, the invention relates to a compound of Formula (I), for its use in the treatment of a Cannabinoids-Related Disorder. Indeed, the compound of the invention is in vivo very potent in inhibiting the effects of THC, and is able to inhibit both unconditioned and conditioned effects of THC including THC self-administration and reinstatement in THC seeking in non-human primates.

  本发明一般涉及一种特定的孕酮衍生物，用于治疗大麻素相关障碍。更具体地，该发明涉及一种式（I）的化合物，用于治疗大麻素相关障碍。事实上，该发明的化合物在体内对THC的效果具有很强的抑制作用，并且能够抑制THC的非条件和条件效应，包括THC的自我管理以及在非人类灵长类动物中寻求THC的恢复。
• Immunoassay for cyclopropylindole based synthetic cannabinoids, metabolites and derivatives thereof
  申请人：Randox Laboratories Ltd.

  公开号：EP2781527A1

  公开（公告）日：2014-09-24

  The invention relates to the detection and quantification of cyclopropylindole based synthetic cannabinoids UR-144 and XLR-11 by providing antobodies based on novel immunogens. These antobodies can be incorporated into methods and kits for the detection of UR-144, XLR-11 and metabolites or derivatives thereof.

  本发明涉及通过提供基于新型免疫原的抗体来检测和定量环丙基吲哚类合成大麻素 UR-144 和 XLR-11。 这些抗体可纳入检测 UR-144、XLR-11 及其代谢物或衍生物的方法和试剂盒中。
• Nuclear magnetic resonance implemented synthetic indole and indazole cannabinoid detection, identification, and quantification
  申请人：HOFSTRA UNIVERSITY

  公开号：US11085891B2

  公开（公告）日：2021-08-10

  The present invention provides a method for detecting synthetic indole and indazole cannabinoids in a sample known or suspected to contain a synthetic indole or indazole cannabinoid in the absence of chromatography. A deuterated solvent is added to the solid sample, creating a suspension. The synthetic cannabinoid is detected in the suspension by analysis of the sample NMR spectrum. When one-dimensional proton NMR is used, detection of a first peak between 8.00 and 8.50 ppm and a second peak between 4.00 and 4.40 ppm, indicates the presence of a synthetic indole or indazole cannabinoid. When two-dimensional Correlation Spectroscopy (COSY) NMR is used, detection of a first spot between 6.50 and 9.00 ppm and a second spot between 1.50 and 4.50 ppm indicates the presence of a synthetic indole or indazole cannabinoid.

  本发明提供了一种在不使用色谱法的情况下检测已知或怀疑含有合成吲哚或吲唑大麻素的样品中合成吲哚和吲唑大麻素的方法。向固体样品中加入氚代溶剂，形成悬浮液。通过分析样品的 NMR 光谱来检测悬浮液中的合成大麻素。使用一维质子核磁共振时，如果检测到 8.00 至 8.50 ppm 之间的第一个峰和 4.00 至 4.40 ppm 之间的第二个峰，则表明存在合成吲哚或吲唑大麻素。当使用二维相关光谱（COSY）核磁共振时，检测到 6.50 至 9.00 ppm 之间的第一个光斑和 1.50 至 4.50 ppm 之间的第二个光斑，表明存在合成吲哚或吲唑大麻素。
• NUCLEAR MAGNETIC RESONANCE BASED SYNTHETIC INDOLE AND INDAZOLE CANNABINOID DETECTION, IDENTIFICATION, AND QUANTIFICATION
  申请人：Hofstra University

  公开号：EP2989452B1

  公开（公告）日：2021-09-29
• NUCLEAR MAGNETIC RESONANCE IMPLEMENTED SYNTHETIC INDOLE AND INDAZOLE CANNABINOID DETECTION, IDENTIFICATION, AND QUANTIFICATION
  申请人：HOFSTRA UNIVERSITY

  公开号：US20160084779A1

  公开（公告）日：2016-03-24

  The present invention provides a method for detecting synthetic indole and indazole cannabinoids in a sample known or suspected to contain a synthetic indole or indazole cannabinoid. A deuterated solvent is added to the solid sample, creating a suspension. The suspension is mixed to release the cannabinoid from the solid sample. The suspension is subject to a NMR spectroscopy process to produce a sample NMR spectrum. The synthetic cannabinoid is detected in the suspension by analysis of the sample NMR spectrum. When one-dimensional proton NMR is used, detection of a first peak between 8.00 and 8.50 ppm and a second peak between 4.00 and 4.40 ppm, indicates the presence of a synthetic indole or indazole cannabinoid. When two-dimensional Correlation Spectroscopy (COSY) NMR is used, detection of a first spot between 6.50 and 9.00 ppm and a second spot between 1.50 and 4.50 ppm indicates the presence of a synthetic indole or indazole cannabinoid. The method is performed in the absence of chromatography and optionally, may be used to quantify the amount of synthetic cannabinoid.