番木鳖碱 | 57-24-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 马钱子生物碱
• 中文名称: 番木鳖碱
• 中文别名: 马钱子碱；士的宁；毒鼠碱；二甲双胍；双甲胍；马钱子碱；士得宁；番木鳌碱；
• 英文名称: strychnidin-10-one
• 英文别名: Strychnine；[3H]-strychnine；Nux Vomica；(4aR,5aS,8aR,13aS,15aS,15bR)-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one
• CAS: 57-24-9
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.418
• InChiKey: QMGVPVSNSZLJIA-FVWCLLPLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

在摄入后几分钟内，士的宁在尿液中保持不变，但其主要的清除和解毒途径是通过肝脏的氧化代谢。

Within a few minutes of ingestion, strychnine appears unchanged in the urine, but the major route for removal and detoxification is oxidative hepatic metabolism.

来源:Hazardous Substances Data Bank (HSDB)

代谢

对某些生物碱与大鼠肝微粒体结合光谱的研究发现，布鲁辛、莨菪碱和马钱子碱属于I型化合物，而波尔定、吐根碱、尼古丁、蛇根碱和血根碱显示出II型结合。

Studies on the binding spectra of certain alkaloids with rat liver microsomes revealed that brucine, scopolamine and strychnine are type I compounds, whereas boldine, emetine, nicotine, reserpine and sanguinarine show type II binding.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在体外研究中，对大鼠和家兔肝脏9000克上清液中的马钱子碱代谢进行了研究。马钱子碱的代谢明显被细胞色素P450抑制剂（SKF-525A和辛基胺）所抑制，而仅被含有黄素腺嘌呤二核苷酸的单加氧酶抑制剂（甲巯咪唑）轻微抑制。通过家兔肝脏在体外形成的五种代谢物被分离和纯化。其中三种通过紫外线、核磁共振和质谱与真实样本比较被鉴定为2-羟基马钱子碱、马钱子碱N-氧化物和21α,22α-二羟基-22-羟基马钱子碱。此外，另外两种代谢物通过光谱测量暂时被鉴定为马钱子碱21,22-环氧化物和11,12-脱氢马钱子碱。通过高效液相色谱法对部分纯化后的这些代谢物的体外形成进行了检测。马钱子碱N-氧化物是主要的代谢物，约占代谢的马钱子碱的15%。所有其他代谢物所占比例小于1%。

The in vitro metabolism of strychnine was studied in 9000-g supernatant fractions from rat and rabbit livers. The metabolism was markedly inhibited by cytochrome p450 inhibitors (SKF-525A and octylamine), but only slightly inhibited by a microsomal Flavine Adenine Dinucleotide containing monooxygenase inhibitor (methimazole). Five metabolites formed in vitro by rabbit liver were isolated and purified. Three of them were identified as 2-hydroxystrychnine, strychnine N-oxide, and 21alpha,22alpha-dihydroxy-22-hydrostrychnine, by comparison with authentic samples by means of UV, NMR, and mass spectrometries. Additionally, 2 other metabolities were tentatively identified as strychnine 21,22-epoxide and 11,12-dehydrostrychnine by spectral measurements. ... The in vitro formation of these metabolites by rabbit liver was detected by high performance liquid chromatography after partial purification. Strychnine N-oxide was the major metabolite and accounted for approximately 15% of the metabolized strychnine. All other metabolites accounted for < 1%. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：马钱子碱是一种固体。它主要用于设置用于松鼠、地鼠、兔子和一些较小啮齿动物的毒饵。饵料通常是含有0.5-1%硫酸盐的彩色谷物。它曾作为兽医药物中的滋补品和中枢刺激剂使用。人类研究：马钱子碱中毒的临床综合征非常典型。最初的症状是面部和颈部肌肉的僵硬和抽搐，动作可能突然。反射兴奋性增强，突然的触觉、视觉或听觉刺激会引起剧烈的 motor 反应。摄入后30分钟内，会出现全身性强直性惊厥和角弓反张。死亡是由于不受控制的癫痫或心脏骤停导致的呼吸暂停造成的脑损伤。在大多数严重马钱子碱中毒的情况下，病人在到达医院之前就会死亡。对人类的致死剂量为30-60 mg/kg。动物研究：兔子玻璃体内注射马钱子碱（0.0012 M）对视网膜电图或光诱导的视神经电位几乎没有影响，但据报道，猫的静脉注射会增加视神经神经元的自发性电活动。对青蛙视网膜的影响也被观察到。马钱子碱对大鼠的毒性具有性别依赖性，雄性对马钱子碱的耐受性高于雌性。在雄性大约8 mg/kg和雌性大约2.5 mg/kg的剂量下，马钱子碱给药28天后没有观察到组织病理学或血液学的变化。给怀孕大鼠注射马钱子碱（一种强大的甘氨酸受体拮抗剂）对胚胎产生了明显的毒性影响。马钱子碱对胚胎的毒性作用与大鼠神经形成期间由视黄醇软脂酸诱导的毒性作用进行了比较，发现马钱子碱在许多异常中比视黄醇软脂酸更强，如无脑儿、普遍发育不全和异常大脑囊泡。狗和猫是更容易受到影响的家畜，认为猪的易感性等同于狗，而马能够耐受相对较大剂量的马钱子碱。牛对摄入马钱子碱或印度防己的抵抗力要强得多，这可能是因为它在瘤胃中部分被破坏。马钱子碱在大多数物种中的致死剂量在0.2和1.0 mg/kg之间。生态毒性研究：家禽急性口服摄入后中毒迹象：羽毛蓬松或紧紧贴附在身体上，低或高抬举，共济失调或不协调，肌束震颤，流涎，震颤，过度敏感，肌肉紧张，反复抽搐，厌食，心动过速，无法移动，剧烈抽搐或角弓反张。

IDENTIFICATION AND USE: Strychnine is a solid. It is used chiefly in poison baits set for squirrels, gophers, rabbits, and some lesser rodents. Baits are usually colored grains containing 0.5-1% of the sulfate. It has been used as Has been used as a tonic and central stimulant in veterinary medicine. HUMAN STUDIES: The clinical syndrome of strychnine poisoning is very characteristic. The initial symptoms are stiffness and twitching of face and neck muscles and movements may be abrupt. Reflex excitability is heightened and sudden tactile, visual, or acoustic stimuli induce violent motor responses. Within 30 min after ingestion, full tetanic convulsion and opisthotonos develop. Death is due to brain damage secondary to apnea from uncontrolled seizures or cardiac arrest. In most severe cases of strychnine poisoning, the patient dies before reaching the hospital. The lethal dose to man 30-60 mg/kg. ANIMAL STUDIES: Intravitreal injection of strychnine (0.0012 M) in rabbits has had little or no effect on the ERG or light-induced optic nerve potential, but IV injection in cats has been reported to increase the spontaneous electrical activity of the optic nerve neurons. An effect on frog retina has also been observed. The toxicity of strychnine in rats was sex-dependent with the male being more tolerant to strychnine than the female. At doses of about 8 mg/kg in males and 2.5 mg/kg in females no histopathological or hematological changes were observed following administration of strychnine for 28 days. Administering strychnine, a potent antagonist of glycine receptors, to pregnant rats caused marked toxic effects on the embryos. The embryotoxic effects of strychnine were compared with those induced by retinal palmitate during rat neurulation, and it was found that strychnine was stronger than retinal palmitate in a number of abnormalities such as anencephaly, general aplasy and abnormal cerebral vesicles. The dog and cat are the more susceptible of the domestic animals, pigs are believed to be as susceptible as dogs, and horses are able to tolerate relatively larger amounts of strychnine. Cattle are much more resistant to the ingestion of strychnine or nux vomica, presumably because of its partial destruction in the rumen. The lethal dose of strychnine in most species is somewhere between 0.2 and 1.0 mg/kg. ECOTOXICITY STUDIES: Signs of intoxication following acute oral intake in fowls: feathers fluffed or held tightly against the body, low or high carriage, ataxia or asynergy, fasciculation, salivation, tremors, hyperacusis, muscle tenseness, recurring convulsions, anorexia, tachycardia, immobility, violent convulsions or opisthotonos.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

strychnine 作为抑制剂或对strychnine敏感的甘氨酸受体的拮抗剂，是一种位于脊髓和大脑中的配体门控氯通道。(L1230)

Strychnine acts as an antagonist at the inhibitory or strychnine-sensitive glycine receptor, a ligand-gated chloride channel in the spinal cord and the brain. (L1230)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

窒息或极度疲惫可能导致死亡。

Death may result from asphyxia or sheer exhaustion. (L1230)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

该物质可以通过吸入其气溶胶和通过吞食被吸收进人体。

The substance can be absorbed into the body by inhalation of its aerosol and by ingestion.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

吸收、分配和排泄

一种快速、特异且灵敏的液相色谱-串联质谱（LC-MS/MS）方法被开发和验证，用于同时测定大鼠血浆中的士的宁、马钱子碱、士的宁N-氧化物和马钱子碱N-氧化物。血浆样本通过简单的甲醇沉淀蛋白进行预处理，以盐酸麻黄碱作为内标。色谱分离在一个ZORBAX Eclipse XDB-C18柱（2.1 x 150 mm, 3.5 um）上进行，通过梯度洗脱甲醇和10mM醋酸铵（用甲酸调至pH 4.0）。通过质谱法以正离子多重反应监测（MRM）模式的TurboIonSpray离子化（ESI）入口对分析物进行定量。结果显示，士的宁、马钱子碱的校准曲线在0.510至约306.3 ng/mL的浓度范围内线性良好，士的宁N-氧化物和马钱子碱N-氧化物的校准曲线在0.102至约306.0 ng/mL的浓度范围内线性良好。日内和日间精密度均小于14.9%，准确度在三个QC水平上为89.4至113%。验证后的方法成功应用于口服士的宁、马钱子碱、士的宁N-氧化物和马钱子碱N-氧化物单体及马钱子总生物碱后在大鼠血浆中的药代动力学研究。口服马钱子总生物碱后，随着剂量增加，士的宁和马钱子碱的Cmax和AUC0-t也相应增加，并与口服剂量成正比。在比较药代动力学研究中，单体与马钱子总生物碱在Cmax和AUC等药代动力学参数上没有显著差异。与马钱子总生物碱组相比，单体的士的宁和马钱子碱的平均Cmax和AUC略有增加，这表明马钱子中的其他生物碱可能会降低体内士的宁和马钱子碱的吸收。

A rapid, specific and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the simultaneous determination of strychnine, brucine, strychnine N-oxide and brucine N-oxide in rat plasma. Plasma samples were pretreated via simple protein precipitation with methanol and ephedrine hydrochloride was used as internal standard. Chromatographic separation was carried out on an ZORBAX Eclipse XDB-C18 column (2.1 x 150 mm, 3.5 um) by gradient elution with methanol and 10mM ammonium acetate (adjusted to pH 4.0 with formic acid). The quantification of the analytes was performed by mass spectrometry with TurboIonSpray ionization (ESI) inlet in the positive ion multiple reaction monitoring (MRM) mode. The results showed that the calibration curve was linear in the concentration range of 0.510 to approximately 306.3 ng/mL for strychnine, brucine and 0.102 to approximately 306.0 ng/mL for strychnine N-oxide and brucine N-oxide, respectively. The intra- and inter-day precisions were less than 14.9%, and the accuracy ranged from 89.4 to 113% at three QC levels for the 4 analytes. The validated method was successfully applied to the pharmacokinetic study of strychnine, brucine, strychnine N-oxide and brucine N-oxide in rat plasma after oral administration of each monomer and the total alkaloids from Semen Strychni. After single oral administration of the total alkaloids from Semen Strychni at 4 dose levels, Cmax, AUC0-t of strychnine and brucine increased and were proportional to the oral doses. In comparative pharmacokinetics studies, no significant difference was found between each monomer and the total strychnos alkaloids on the pharmacokinetic parameters such as Cmax and AUC. Mean Cmax and AUC of strychnine and brucine were slight increased in the monomer groups in comparison to the total strychnos alkaloids groups, which suggested that some other alkaloids in the Semen Strychni may decrease the absorption of strychnine and brucine in body.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

为了研究甘草素（Liq）对士的宁（Str）在Caco-2细胞单层模型中转运的影响，确定了单独使用Str以及与Liq共同使用时Str的转运参数，如表观渗透系数（P app (B-->A) 和 P app (A-->B)）和累计转运量（TRcum），并进行比较分析。同时，还研究了药物浓度、输送时间、P-糖蛋白（P-gp）抑制剂维拉帕米和输送液pH值对Str转运的影响。结果表明，Str在Caco-2细胞单层模型中的吸收良好，被动转运是Str在Caco-2单层模型中的主要肠道吸收机制，同时伴随着P-gp介导的排泄作用。Liq增强了Str的吸收。此外，输送液的pH值对Str的排泄转运有显著影响。

To study the effect of liquiritin (Liq) on the transport of strychnine (Str) in Caco-2 cell monolayer model, the transport parameters of Str, such as apparent permeability coefficient (P app (B-->A) and P app (A-->B)) and cumulative transport amount (TRcum), were determined and comparatively analyzed when Str was used solely and co-used with Liq. The effect of drug concentrations, conveying times, P-glycoprotein (P-gp) inhibitor verapamil and conveying liquor pH values on the transport of Str were also investigated. The results indicated that the absorption of Str in Caco-2 cell monolayer model was well and the passive transference was the main intestinal absorption mechanism of Str in the Caco-2 monolayer model, along with the excretion action mediated by P-gp. Liq enhanced the absorption of Str. Meanwhile, conveying liquor pH value had significant influence on the excretion transport of Str.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一种简单且低成本的高效液相色谱-紫外吸收检测方法被开发和验证，用于同时测定马钱子加工品中含量最丰富的生物碱士的宁和布鲁辛，在大鼠的肾脏、肝脏、脾脏、肺、心脏、胃、小肠、大脑和血浆中的分布。样品在高效液相色谱之前采用简单的液-液萃取处理。不同组织或血浆样品的定量下限在0.039-0.050微克/毫升范围内。提取回收率在71.63%至98.79%之间。线性范围是0.05-2微克/毫升，相关系数超过0.991。日内和日间精密度小于15%。然后使用该方法测量了静脉注射1毫克/千克马钱子加工品提取的粗生物碱组分（CAF）后，士的宁和布鲁辛在不同组织中的分布。结果显示，士的宁和布鲁辛具有相似的组织分布特征。在肾脏中观察到最高水平，而在大脑中观察到最低水平。这表明肾脏可能是原型士的宁和布鲁辛的主要排泄器官。还推断出土的宁和布鲁辛难以穿越血脑屏障。此外，在大鼠组织中没有发现士的宁和布鲁辛的长期积累。

A simple and low-cost HPLC method with UV absorbance detection was developed and validated to simultaneously determine strychnine and brucine, the most abundant alkaloids in the processed Semen Strychni, in rat tissues (kidney, liver, spleen, lung, heart, stomach, small intestine, brain and plasma). The tissue samples were treated with a simple liquid-liquid extraction prior to HPLC. The LOQs were in the range of 0.039-0.050 ug/mL for different tissue or plasma samples. The extraction recoveries varied from 71.63 to 98.79%. The linear range was 0.05-2 ug/mL with correlation coefficient of over 0.991. The intra- and inter-day precision was less than 15%. Then the method was used to measure the tissue distribution of strychnine and brucine after intravenous administration of 1 mg/kg crude alkaloids fraction (CAF) extracted from the processed Semen Strychni. The results revealed that strychnine and brucine possessed similar tissue distribution characterization. The highest level was observed in kidney, while the lowest level was found in brain. It was indicated that kidney might be the primary excretion organ of prototype strychnine and brucine. It was also deduced that strychnine and brucine had difficulty in crossing the blood-brain barrier. Furthermore, no long-term accumulation of strychnine and brucine was found in rat tissues.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

士的宁（马钱子碱）会迅速从胃肠道的粘膜和鼻腔吸收，但不会通过皮肤吸收。药物在组织中的分布也很快，同时它会被肝脏酶代谢成几种无毒的极性产物。只有5-20%的完整生物碱会通过尿液排出。

Strychnine is rapidly absorbed from the gastrointestinal tract and nasal mucosa but not through the skin. Distribution of the drug in tissues is also rapid as is its metabolism to several nontoxic polar products bu hepatic enzymes. Only 5-20% of the intact alkaloid is excreted in urine.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  番木鳖碱 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以29%的产率得到异士的宁
  参考文献：
  名称：

  （-）-Strychnine合成Bis-Strychnos生物碱（–）-Sungucine，（–）-异双胍和（–）-Strychnogucine B

  摘要：

  它开发了一种简明的合成路线，从而从市售（-）-士古丁碱中首次合成了双-士麦碱生物碱（-）-香豆碱，（-）-异sungucine和（-）-士丁香碱B。通过采用高度收敛的合成策略，证明了两种士的诺单体都可以从市售（-）-士的宁中高效制备。招募了古老的曼尼希（Mannich）反应，以仿生方式加入了两种Strychnos单体。随后的差向异构和烯烃异构化产生了（–）-甜菊糖B。官能团操纵将（–）-甜菊糖B转化为（–）-sungucine和（–）-isosungucine。计算化学被用来合理化关键步骤的区域化学过程，以达到双-Strychnos目标。

  DOI：

  10.21577/0103-5053.20180217
• 作为产物：
  描述：

  1-tert-butyldimethylsilanyloxymethyl-6-vinyloxycarbonyloxy-1-cyclohexene 在 palladium diacetate chromium(VI) oxide 、 盐酸 、 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 palladium diacetate 、 氢氧化钾 、 lithium aluminium tetrahydride 、 甲酸 、 potassium hexamethyldisilazane 、 四丁基氯化铵 、 sodium isopropylate 、 三溴化磷 、 lithium carbonate 、 sodium naphthalenide 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 silver carbonate 、 2,2'-双(二苯基氧膦)-1,1'-联萘 、 三氟乙酸 、 二甲基苯基磷 、 3,5-二甲基苯酚 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 76.25h， 生成 番木鳖碱
  参考文献：
  名称：

  马钱子吲哚生物碱的新型通用合成途径：使用钯催化的不对称烯丙基取代的 (-)-Tubifoline、(-)-Dehydrotubifoline 和 (-)-Strychnine 的全合成

  摘要：

  建立了钯催化不对称烯丙基取代合成2-取代环己烯胺衍生物的方法。在 Pd(2)dba(3).CHCl(3) 和 (S)-BINAPO 的存在下，在 THF 中用邻溴-N-甲苯磺酰苯胺处理 2-甲硅烷氧基甲基环己烯醇衍生物，得到 80% ee 的环己烯胺衍生物％ 屈服。进行Heck反应以高产率生产假吲哚衍生物。使用这种方法，我们合成了假吲哚衍生物 7，将其从乙醇中重结晶，得到光学纯的化合物。从这种化合物中，可以合成四环酮 13，它应该是合成吲哚生物碱的有用中间体。(-)-dehydrotubifoline、(-)-tubifoline 和 (-)-strychnine 的全合成是从 13 实现的。

  DOI：

  10.1021/ja029382u
• 作为试剂：
  描述：

  Alpha-甲基-DL-天冬氨酸 在 番木鳖碱 作用下， 生成 (R)-(-)-2-氨基-2-甲基丁二酸
  参考文献：
  名称：

  Pfeiffer; Heinrich, Journal fur praktische Chemie (Leipzig 1954), 1936, vol. <2>146, p. 105,107

  摘要：

  DOI：

文献信息

• [EN] NOVEL ANTIVIRAL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS ANTIVIRAUX
  申请人：UNIV LEUVEN KATH

  公开号：WO2014170368A1

  公开（公告）日：2014-10-23

  The present invention relates to a series of novel compounds and derivatives thereof, methods to prevent or treat viral infections by using the novel compounds, processes for their preparation, their use to treat or prevent viral infections and their use to manufacture a medicine to treat or prevent viral infections, preferably infections with viruses belonging to the family of the Togaviridae and more preferably infections with chikungunya virus (CHIKV).

  本发明涉及一系列新化合物及其衍生物，利用这些新化合物预防或治疗病毒感染的方法，以及它们的制备过程，用于治疗或预防病毒感染以及用于制造治疗或预防病毒感染的药物，最好是用于治疗属于Togaviridae家族的病毒，更好地是用于治疗寨卡病毒感染。
• [EN] MICROBIOCIDAL OXADIAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'OXADIAZOLE MICROBIOCIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2017157962A1

  公开（公告）日：2017-09-21

  Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially fungicides.

  式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
• [EN] INSECTICIDAL TRIAZINONE DERIVATIVES<br/>[FR] DÉRIVÉS DE TRIAZINONE INSECTICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2013079350A1

  公开（公告）日：2013-06-06

  Compounds of the formula (I) or (I'), wherein the substituents are as defined in claim 1, are useful as pesticides.

  式(I)或(I')的化合物，其中取代基如权利要求1所定义的那样，可用作杀虫剂。
• Integrase inhibitors
  申请人：Cai R. Zhenhong

  公开号：US20080058315A1

  公开（公告）日：2008-03-06

  Tricyclic compounds, protected intermediates thereof, and methods for inhibition of HIV-integrase are disclosed.

  三环化合物，其受保护的中间体，以及用于抑制HIV整合酶的方法被披露。
• [EN] TRIPARTITE MODULATORS OF ENDOSOMAL G PROTEIN-COUPLED RECEPTORS<br/>[FR] MODULATEURS TRIPARTITES DE RÉCEPTEURS COUPLÉS AUX PROTÉINES G DES ENDOSOMES
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2017112792A1

  公开（公告）日：2017-06-29

  The present invention relates to tripartite compounds comprising a modulator moiety for endosomal G protein-coupled receptors like neurokinin-1 receptor, a linker and a lipid anchor suitable for anchoring the tripartite compound into a plasma membrane. The present invention also relates to a prodrug and a pharmaceutical composition comprising the tripartite compound and the use of the tripartite compound for the treatment of a disease or disorder mediated by endosomal G protein-coupled receptors signalling like NK1R signalling.

  本发明涉及三部分化合物，包括用于内体高尔基蛋白偶联受体（如神经激肽-1受体）的调节子基团，一个连接物和一个适合将三部分化合物锚定到细胞膜的脂质锚。本发明还涉及一种前药和含有三部分化合物的药物组合物，以及利用三部分化合物治疗由内体高尔基蛋白偶联受体信号传导介导的疾病或紊乱的用途。

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