替可克肽 | 16960-16-0

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 促肾上腺皮质激素类药
• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 中文名称: 替可克肽
• 中文别名: 促皮质24肽；二十四肽促皮质素
• 英文名称: tetracosactide
• 英文别名: H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-Lys-Val-Tyr-Pro；α1-24-corticotropin；[125I]-adrenocorticotropin(1-24)；(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-carboxybutanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]acetyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]acetyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carboxylic acid
• CAS: 16960-16-0
• 化学式: C₁₃₆H₂₁₀N₄₀O₃₁S
• 分子量: 2933.48
• InChiKey: ZOEFCCMDUURGSE-SQKVDDBVSA-N

物化性质

• 密度：
  1.47±0.1 g/cm3(Predicted)
• 溶解度：
  微溶于水。

计算性质

• 辛醇/水分配系数(LogP)：
  -7.9
• 重原子数：
  208
• 可旋转键数：
  96
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  1180
• 氢给体数：
  42
• 氢受体数：
  41

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毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，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。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入性肺炎。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)

毒理性

• 人类毒性摘录

/病例报告/ 合成1-24肾上腺皮质激素（tetracosactid，Synacthen）在临床医学中用于诊断和治疗目的。由于对内源性肾上腺皮质激素生产的非生理性刺激，可能会出现副作用。对tetracosactid的过敏反应是罕见的。在一例14岁的支气管哮喘女孩静脉注射tetracosactid后观察到了导致死亡的过敏性休克。使用双抗体法在死亡后的血清和腹水中可以检测到肾上腺皮质激素抗体。

/CASE REPORTS/ Synthetic 1-24adrenocorticotrophin (tetracosactid, Synacthen) is used in clinical medicine for diagnostic and therapeutic purposes. Side effects may occur due to unphysiological stimulation of endogenous adrenocortical hormone production. Allergic reactions to tetracosactid are rare. Anaphylactic shock leading to death was observed after intravenous injection of tetracosactid in a 14-year-old girl with bronchial asthma. Adrenocorticotrophin antibodies could be demonstrated after death in serum and ascitic fluid using the double antibody method.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

病例报告/某些糖尿病患者存在发展为高钾血症的较高风险。这一群体包括葡萄糖诱导的高钾血症患者，他们可能存在肾功能不全、低肾素性低醛固酮血症，或其他影响醛固酮释放或作用的障碍。在展示这种异常的一个不寻常的案例中，两名糖尿病患者（构成了我们报告的基础）在接受了 cosyntropin（合成促肾上腺皮质激素）给药后，出现了明显的血糖升高和高钾血症。据我们所知，这种肾上腺皮质激素（ACTH）刺激测试的并发症尚未有先前报道。因此，应该强调的是，将cosyntropin作为诊断剂的使用可能会在糖尿病患者的易感亚群中引发严重的高血糖和高钾血症。

/CASE REPORTS/ Some patients with diabetes mellitus are at increased risk for the development of hyperkalemia. Included in this group are patients with glucose-induced hyperkalemia who may have renal insufficiency, hyporeninemic hypoaldosteronism, or other impediments to the release or action of aldosterone. In an unusual demonstration of this abnormality, two patients with diabetes, who form the basis of our report, became markedly hyperglycemic and hyperkalemic after cosyntropin administration. To our knowledge, this complication of adrenocorticotropic hormone (ACTH) stimulation testing has not been previously reported. It should therefore be emphasized that the use of cosyntropin as a diagnostic agent can provoke severe hyperglycemia and hyperkalemia in a susceptible subgroup of patients with diabetes mellitus.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

cosyntropin是经IM给药后迅速吸收的。

Cosyntropin is rapidly absorbed following IM administration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Adsorption of tetracosactrin on to zinc phosphate provides for sustained release of the active substance from the intramuscular injection site. After an injection of a mg Synacthen Depot IM, the radioimmunologically determined plasma concentrations of tetracosactrin lie for 12 hours between 200 and 300 pg/mL. Tetracosactrin has an apparent distribution volume of approximately 0.4 L/kg. /Tetracosactrin zinc phosphate complex - depot (NOT available in US)/

Adsorption of tetracosactrin on to zinc phosphate provides for sustained release of the active substance from the intramuscular injection site. After an injection of a mg Synacthen Depot IM, the radioimmunologically determined plasma concentrations of tetracosactrin lie for 12 hours between 200 and 300 pg/mL. Tetracosactrin has an apparent distribution volume of approximately 0.4 L/kg. /Tetracosactrin zinc phosphate complex - depot (NOT available in US)/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

促肾上腺皮质激素的精确分布和代谢命运尚不清楚，但该药物会被许多组织迅速从血浆中清除。促肾上腺皮质激素似乎不会穿过胎盘。

The precise distribution and metabolic fate of cosyntropin is not known, but the drug is rapidly removed from the plasma by many tissues. Cosyntropin apparently does not cross the placenta.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

经肌肉注射后迅速吸收。

Rapidly absorbed following intramuscular administration.

来源:DrugBank

安全信息

• WGK Germany：
  3
• 海关编码：
  2937220000
• RTECS号：
  GM7915000
• 储存条件：
  密封避光保存

制备方法与用途

适应证

替可克肽与促肾上腺皮质激素的作用相同，因此其临床应用范围也与促肾上腺皮质激素相似。由于作用更强且副作用较小的皮质激素更为常用，替可克肽目前主要用于治疗部分克罗恩病、溃疡性结肠炎和风湿性关节炎等少数疾病。对于长期使用皮质激素治疗的患者，可以联合使用替可克肽以预防肾上腺萎缩。此外，替可克肽与促肾上腺皮质激素一样，也用于肾上腺皮质功能检查，但长效替可克肽一般不作为标准的肾上腺皮质功能试验用药。

药代动力学

替可克肽是一种由24个氨基酸组成的多肽，其结构与促肾上腺皮质激素前1～24个氨基酸相同。静脉给药后能够迅速提高血浆中的皮质醇水平；在需要维持较高血皮质醇浓度时，需持续进行静脉点滴给药。肌内注射后，血皮质醇水平会在1小时达到峰值，并可在接下来的约24小时内保持升高状态。

不良反应

替可克肽与促肾上腺皮质激素的不良反应相似。大量使用可能会引起水钠潴留、高血压、精神异常、糖耐量下降、蛋白质消耗、骨质疏松、低血钾、月经失调、色素沉着及痤疮等现象。少数患者可能出现过敏反应，但发生率较促肾上腺皮质激素低。

生物活性

替可克肽（INN）是肾上腺皮质激素类似物，具有刺激肾上腺皮质分泌的生物活性。

化学性质

替可克肽是一种人工合成的24肽促皮质素类似物，其氨基酸序列与天然促皮质素（人、牛、猪）氨基端前24个氨基酸相同，与天然ACTH具有相同的生理活性。该药物一般不会产生抗体反应且无严重副作用，特别适用于对天然猪促皮质素有过敏反应或无效的患者。

每毫升替可克肽的作用相当于100单位的天然促皮质素。口服此药无效；静注后30分钟内血中皮质醇浓度迅速升高，约30分钟后从血液中消失；肌内注射后1小时达到最大血药浓度，其作用可持续4小时以上。

参考质量标准

• 外观：白色粉末
• 纯度（HPLC）≥98.0%
• 单杂≤1.0%
• 醋酸根含量5.0%～12.0%
• 水分含量≤10.0%
• 肽含量≥80.0%

用途

用于诊断肾上腺皮质功能不全；也可用于治疗风湿病、风湿性关节炎、皮肤病及休克等。

不良反应和禁忌：常见的过敏反应如瘙痒、面红、荨麻疹、支气管痉挛等较促皮质素少。偶尔会出现晕厥或虚脱的情况。长期或过量使用可能会导致浮肿、高血压、低血钾、色素沉着及诱发感染，对天然促皮质素过敏的患者应慎用。

反应信息

• 作为反应物：
  描述：

  替可克肽 、 diethyl 4-cyclohexyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate 在 三氟乙酸 作用下， 以 2,2,2-三氟乙醇 为溶剂， 反应 9.0h， 以47%的产率得到
  参考文献：
  名称：

  通过可见光促进的 CH 烷基化修饰组氨酸特异性肽

  摘要：

  组氨酸（His）带有独特的杂芳族咪唑侧链，在多肽和蛋白质中发挥着不可替代的功能作用。现有的位点选择性组氨酸修饰策略主要依赖于适度亲核的咪唑基团的 N 取代反应，其固有地受到赖氨酸和半胱氨酸残基的干扰。组氨酸的化学选择性修饰仍然是肽化学中最困难的挑战之一。在此，我们报告了在可见光促进条件下使用 C4-烷基-1,4-二氢吡啶 (DHP) 试剂通过自由基介导的化学选择性 CH 烷基化组氨酸进行肽修饰。该方法通过 Minisci 型反应途径利用咪唑环的亲电反应性。该方法对肽和 DHP 烷基化试剂表现出异常广泛的范围。其效用已在一系列重要的肽药物、复杂的天然产物和小蛋白质中得到证明。与 N 取代反应不同，改性咪唑环的未取代氮基团在 CH 烷基化产物中是保守的。

  DOI：

  10.1021/jacs.9b09127

文献信息

• ANTHELMINTIC COMPOUNDS AND COMPOSITIONS AND METHOD OF USING THEREOF
  申请人：Meng Charles Q.

  公开号：US20140142114A1

  公开（公告）日：2014-05-22

  The present invention relates to novel anthelmintic compounds of formula (I) below: wherein Y and Z are independently a bicyclic carbocyclic or a bicyclic heterocyclic group, or one of Y or Z is a bicyclic carbocyclic or a bicyclic heterocyclic group and the other of Y or Z is alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, heterocyclyl or heteroaryl, and variables X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 and X 8 are as defined herein. The invention also provides for veterinary compositions comprising the anthelmintic compounds of the invention, and their uses for the treatment and prevention of parasitic infections in animals.

  本发明涉及以下式（I）的新型驱虫化合物： 其中 Y和Z分别是双环碳环或双环杂环基团，或者Y或Z中的一个是双环碳环或双环杂环基团，另一个是烷基，烯基，炔基，环烷基，苯基，杂环基或杂芳基，以及变量X 1 ，X 2 ，X 3 ，X 4 ，X 5 ，X 6 ，X 7 和X 8 如本文所定义。本发明还提供了包含本发明的驱虫化合物的兽药组合物，以及它们用于治疗和预防动物寄生虫感染的用途。
• [EN] ANTHELMINTIC DEPSIPEPTIDE COMPOUNDS<br/>[FR] COMPOSÉS DEPSIPEPTIDIQUES ANTHELMINTHIQUES
  申请人：MERIAL INC

  公开号：WO2018093920A1

  公开（公告）日：2018-05-24

  The present invention provides cyclic depsipeptide compounds of formula (I) wherein the stereochemical configuration of at least one carbon atom bearing the groups Cy1, Cy2, R1, R2, R3, R4, Ra and Rb is inverted compared with the naturally occurring cyclic depsipeptide PF1022A. The invention also provides compositions comprising the compounds that are effective against parasites that harm animals. The compounds and compositions may be used for combating parasites in or on mammals and birds. The invention also provides for an improved method for eradicating, controlling and preventing parasite infestation in birds and mammals.

  本发明提供了公式（I）的环状脱氨肽化合物，其中至少一个碳原子的立体化学构型与自然存在的环状脱氨肽PF1022A的基团Cy1、Cy2、R1、R2、R3、R4、Ra和Rb相比发生了倒置。该发明还提供了包含这些化合物的组合物，对危害动物的寄生虫具有有效性。这些化合物和组合物可用于对抗哺乳动物和鸟类体内或体表的寄生虫。该发明还提供了一种改进的方法，用于根除、控制和预防鸟类和哺乳动物的寄生虫感染。
• [EN] BINDING-SITE MODIFIED LECTINS AND USES THEREOF<br/>[FR] LECTINES DE SITE DE LIAISON MODIFIÉES ET USAGE CORRESPONDANT
  申请人：SMARTCELLS INC

  公开号：WO2010088261A1

  公开（公告）日：2010-08-05

  In one aspect, the disclosure provides cross-linked materials that include multivalent lectins with at least two binding sites for glucose, wherein the lectins include at least one covalently linked affinity ligand which is capable of competing with glucose for binding with at least one of said binding sites; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with glucose for binding with the lectins at said binding sites and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between lectins and affinity ligands on different conjugates. These materials are designed to release amounts of conjugate in response to desired concentrations of glucose. Depending on the end application, in various embodiments, the conjugates may also include a drug and/or a detectable label.

  在一个方面，该公开提供了包括多价凝集素的交联材料，其中该多价凝集素具有至少两个葡萄糖结合位点，其中该凝集素包括至少一个与亲和配体共价连接的亲和配体，该亲和配体能够与至少一个所述结合位点中的葡萄糖竞争结合；以及包括绑定到共轭框架的两个或更多个独立亲和配体的共轭物，其中这两个或更多个亲和配体与葡萄糖在所述结合位点上与凝集素竞争结合，其中由于不同共轭物上的凝集素和亲和配体之间的非共价相互作用，共轭物在材料内交联。这些材料旨在根据所需葡萄糖浓度释放共轭物的量。根据最终应用，在各种实施例中，共轭物还可以包括药物和/或可检测标记。
• [EN] ANTI PARASITIC DIHYDROAZOLE COMPOUNDS AND COMPOSITIONS COMPRISING SAME<br/>[FR] DIHYDROAZOLES ANTIPARASITAIRES ET COMPOSITIONS LES INCLUANT
  申请人：MERIAL LTD

  公开号：WO2011075591A1

  公开（公告）日：2011-06-23

  The present invention relates to novel dihydroazole of formula (I) and salts thereof: Wherein R1, A1, A2, G, X and Y are as defined in the description, compositions thereof, processes for their preparation and their uses to prevent or treat parasitic infections or infestations in animals and as pesticides.

  本发明涉及式(I)的新型二氢咪唑及其盐：其中R1、A1、A2、G、X和Y如描述中所定义，以及它们的组合物、制备方法以及它们用于预防或治疗动物寄生虫感染或寄生虫侵袭以及作为杀虫剂的用途。
• [EN] PYRAZOLO [4, 3-D] PYRIMIDINES USEFUL AS KINASE INHIBITORS<br/>[FR] PYRAZOLO[4,3-D]PYRIMIDINES UTILES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143144A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。