海克替啶 | 141-94-6

• 物质功能分类: 原料药 - 人工合成抗感染类药 - 抗真菌类药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 海克替啶
• 中文别名: 六丁啶；5-氨基-1,3-二(2-乙基己基)-5-甲基六氢嘧啶
• 英文名称: hexetidine
• 英文别名: Hexetidin；1,3-bis(2-ethylhexyl)-5-methyl-1,3-diazinan-5-amine
• CAS: 141-94-6
• 化学式: C₂₁H₄₅N₃
• mdl: MFCD00010428
• 分子量: 339.608
• InChiKey: DTOUUUZOYKYHEP-UHFFFAOYSA-N

物化性质

• 熔点：
  25°C
• 沸点：
  160 °C/0.4 mmHg (lit.)
• 密度：
  0.889 g/mL at 25 °C (lit.)
• 闪点：
  70°C
• 溶解度：
  可溶于丙酮
• LogP：
  7.150 (est)
• 颜色/状态：
  Liquid
• 蒸汽压力：
  1.54X10-5 mm Hg at 25 °C (est)
• 折光率：
  Index of refraction = 1.4668 at 20 °C/D
• 解离常数：
  pKa = 8.3
• 碰撞截面：
  194 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
• 稳定性/保质期：
  在常温常压下，它保持稳定。

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

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，让患者前倾或将其置于左侧（如果可能的话，头部向下），以保持呼吸道畅通并防止吸入。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，协助通气。通过非重复呼吸面罩以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……。监测休克并如有必要进行治疗……。预见癫痫并如有必要进行治疗……。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，如果患者能够吞咽、有强烈的呕吐反射且不流口水，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……。在去污染后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒物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"，最低流速/。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……。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

人类暴露研究：两百二十名人类受试者在前臂上贴片测试了含有1%洗必泰的软膏；48小时后，212名受试者可以进行重新检查。没有人显示出接触测试材料部位的皮炎或刺激的迹象。两周后，这168名受试者中有168人可以进行重新测试，并且原来的部位再次用于重复贴片测试。没有初级刺激或致敏的证据。

/HUMAN EXPOSURE STUDIES/ Two hundred twenty human subjects were patch tested on the forearm with an ointment containing 1% hexetidine; 48 hours later 212 subjects were available for re-examination. None showed evidence of dermatitis or irritation at the contact site of the test material. Two weeks later 168 of these subjects were available for retesting and the original sites were again used for the repeated patch test. There was no evidence of primary irritation or sensitization.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/症状和体征/ 偶尔报道有接触性皮炎和嗅觉、味觉改变……通过静脉给药具有毒性。5-10% w/v 浓度的己塞啶油溶液在人体中会引起强烈的一级刺激性，但不会引起过敏。

/SIGNS AND SYMPTOMS/ Allergic contact dermatitis and altered olfactory and taste perception have occasionally been reported ... Toxic when administered intravenously. Solutions of hexetidine in oil at concentrations of 5-10% w/v cause strong primary irritations without sensitization in humans.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

由于其阳离子性质，口腔给药后，六亚甲基双胍能被吸收到粘膜和牙菌斑上，且不易被移除。在用放射性同位素标记的六亚甲基双胍的人类研究中，单次口腔冲洗后，它能在颊粘膜上保留8到10小时，并且在应用后长达65小时仍能在口腔组织中检测到其持续存在。

Because of its cationic nature, hexetidine is absorbed to the mucous membranes and dental plaque after oral administration and is not easily removed. Studies in human beings with radiolabeled hexetidine have shown that it is retained on buccal tissues for 8 to 10 hours after a single oral rinse and it has been possible to detect the continued presence of it on the oral tissues for as long as 65 hours after application.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933599090
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338
• 储存条件：
  请将密封于干燥阴凉处保存。

制备方法与用途

生物活性

Hexetidine 是一种兼具抗细菌和抗真菌作用的药物，它还具备局部麻醉、止血、除臭以及预防牙菌斑的功能。

反应信息

• 作为反应物：
  描述：

  海克替啶 在 硫酸 作用下， 反应 2.0h， 以21%的产率得到N1,N3-二(2-乙基己基)-2-甲基丙烷-1,2,3-三胺
  参考文献：
  名称：

  Nitschmann; Capello; Scheidl, Pharmazie, 1997, vol. 52, # 3, p. 195 - 198

  摘要：

  DOI：
• 作为产物：
  描述：

  1,3-二(2-乙基己基)六氢-5-甲基-5-硝基嘧啶 在 甲醇 、 镍 作用下， 100.0 ℃ 、6.86 MPa 条件下， 生成 海克替啶
  参考文献：
  名称：

  The Preparation of Some Hexahydropyrimidines from Nitroparaffins¹

  摘要：

  DOI：

  10.1021/ja01212a073

文献信息

• [EN] PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF<br/>[FR] INHIBITEURS DE LA PRMT5 CONTENANT UNE DIHYDRO- OU TÉTRAHYDRO-ISOQUINOLÉINE ET LEURS UTILISATIONS
  申请人：EPIZYME INC

  公开号：WO2014100730A1

  公开（公告）日：2014-06-26

  Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.

  本文描述了式（A）的化合物，其药学上可接受的盐以及药物组合物。本发明的化合物对抑制PRMT5活性是有用的。还描述了利用这些化合物治疗PRMT5介导的疾病的方法。
• PRMT5 INHIBITORS AND USES THEREOF
  申请人：Duncan Kenneth W.

  公开号：US20190083482A1

  公开（公告）日：2019-03-21

  Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

  本文描述了式（I）的化合物，其药学上可接受的盐以及药物组合物。本发明的化合物对抑制PRMT5活性是有用的。还描述了利用这些化合物治疗PRMT5介导的疾病的方法。
• Kappa agonist compounds and pharmaceutical formulations thereof
  申请人：——

  公开号：US20030144272A1

  公开（公告）日：2003-07-31

  Compounds having kappa opioid agonist activity, compositions containing them and method of using them as analgesics are provided. The compounds of formulae I, II, IIA, III, IIIA, IIIB, IIIB-i, IV and IVA have the structure: 1 2 wherein R 1 , R 2 , R 3 , R 4 ; and X, X 4 , X 5 , X 7 , X 9 ; Y, Z and n are as described in the specification.

  提供具有kappa阿片受体激动剂活性的化合物，含有这些化合物的组合物以及使用它们作为镇痛剂的方法。 具有以下结构的化合物I、II、IIA、III、IIIA、IIIB、IIIB-i、IV和IVA： 1 2 其中 R 1 ，R 2 ，R 3 ，R 4 ；和 X，X 4 ，X 5 ，X 7 ，X 9 ； Y，Z和n如规范中所述。
• Cyclosporins Modified on the MeBmt Sidechain by Heterocyclic Rings
  申请人：Allergan, Inc.

  公开号：US20160289271A1

  公开（公告）日：2016-10-06

  The present invention relates to novel cyclosporin analogs, processes for preparing them, pharmaceutical compositions containing them, and methods for using these analogs and the compositions containing them for the treatment of medical conditions, including but not limited to ocular conditions such as dry eye.

  本发明涉及新型环孢素类似物，制备它们的方法，含有它们的药物组合物，以及利用这些类似物和含有它们的组合物治疗医疗状况的方法，包括但不限于眼部状况如干眼症。
• [EN] ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS<br/>[FR] ANTI-INFECTIEUX A BASE D'ISOTHIAZOLOQUINOLONES ET DE SELS CORRESPONDANTS
  申请人：ACHILLION PHARMACEUTICALS INC

  公开号：WO2005019228A1

  公开（公告）日：2005-03-03

  The invention provides compounds and salts of Formula (I) and Formula (II): which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula (I) and Formula (II). The variables A1, R2, R3, R5, R6, R7, A8 and R9 are defined herein. Certain compounds of Formula (I) and Formula (II) disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula (I) or Formula (II) and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula (I) or Formula (II) as the only active agent or may contain a combination of a compound of Formula (I) or Formula (II) and one or more other active agents. The invention also provides methods for treating microbial infections in animals.

  本发明提供了具有抗菌活性的公式(I)和公式(II)的化合物及盐类：本发明还提供了用于制造公式(I)和公式(II)化合物的新的合成中间体。变量A1、R2、R3、R5、R6、R7、A8和R9在此文中定义。本文披露的某些公式(I)和公式(II)化合物是细菌DNA合成和细菌复制的强效和选择性抑制剂。本发明还提供了含有一种或多种公式(I)或公式(II)化合物以及一种或多种载体、辅料或稀释剂的抗菌组合物，包括药物组合物。这样的组合物可以只含有公式(I)或公式(II)的化合物作为唯一的活性成分，也可以含有公式(I)或公式(II)的化合物与一种或多种其他活性成分的组合。本发明还提供了用于治疗动物微生物感染的方法。

表征谱图