1-[2-(diethylamino)ethylamino]-4-methylthioxanthen-9-one;hydron;chloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫色烯
• 英文名称: 1-[2-(diethylamino)ethylamino]-4-methylthioxanthen-9-one;hydron;chloride
• 化学式: C20H25ClN2OS
• 分子量: 376.9
• InChiKey: LAOOXBLMIJHMFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  57.6
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

毒理性

• 相互作用

研究了二硫代联吡啶酮和环磷酰胺（CYC）在中国仓鼠体内的相互作用，以LD50/7和LD50/30为指标。这些值可能分别指示胃肠道干细胞耗竭和骨髓干细胞耗竭。当100毫克/千克的二硫代联吡啶酮非致死剂量先于CYC注射时，CYC的LD50/7在10小时的治疗间隔内达到最小值470毫克/千克。二硫代联吡啶酮与CYC同时给药对750毫克/千克的对照组LD50/7没有影响，且在二硫代联吡啶酮给药后48小时，LD50/7已恢复到对照组值。当CYC给药先于二硫代联吡啶酮时，LD50/7在5小时的时间间隔内达到最小值610毫克/千克；然而，对于整个序列，它在48小时内的所有时间间隔大约为640毫克/千克。CYC的LD50/30仅因二硫代联吡啶酮的存在而略有降低，表明二硫代联吡啶酮对CYC的骨髓敏感性仅略有影响。这些数据表明，二硫代联吡啶酮可能与CYC损伤以类似它与辐射损伤相互作用的方式相互作用，即通过减少细胞积累和修复亚致死损伤的能力。

The interaction of lucanthone and cyclophosphamide (CYC) was investigated in the Chinese hamster in terms of the LD50/7 and LD50/30. These values may be indicative of gastrointestinal stem cell depletion and bone marrow stem cell depletion, respectively. When a nonlethal dose of 100 mg/kg lucanthone preceded CYC injection, the LD50/7 for CYC reached its minimum value of 470 mg/kg at a treatment interval of 10 hours. Lucanthone administered simultaneously with CYC had no effect on the control LD50/7 of 750 mg/kg, and by 48 hours after lucanthone administration the LD50/7 had returned to the control value. When CYC administration preceded that of lucanthone, the LD50/7 reached a minimum of value of 610 mg/kg at an interval of 5 hours; however, for the entire sequence it was approximately 640 mg/kg over all intervals up to 48 hours. The LD50/30 for CYC was only slightly reduced by the presence of lucanthone, indicating that bone marrow sensitivity to CYC was only marginally affected by lucanthone. These data indicate that lucanthone may interact with CYC damage in much the same way as it interacts with radiation damage, viz, by reducing cellular capacity to accumulate and repair sublethal damage.

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……预计可能出现癫痫，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，用生理盐水连续冲洗每只眼睛……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. 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 normal saline 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 ... . /Poison 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、严重肺水肿或呼吸停止的患者，考虑进行口咽或鼻咽气管插管以控制气道。使用球囊阀面罩装置的正压通气技术可能有益。监测心率和必要时治疗心律失常。开始静脉输液，使用5%葡萄糖盐水（D5W）/SRP: "保持开放"，最小流量/。如果出现低血容量的迹象，使用乳酸钠林格液。注意液体过载的迹象。考虑使用药物治疗肺水肿。对于伴有低血容量迹象的低血压，谨慎输液。注意液体过载的迹象。使用地西泮（安定）治疗癫痫。使用丙美卡因氢氯化物协助眼部冲洗。/毒药A和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 respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/研究了lucanthone和环磷酰胺（CYC）在中国仓鼠体内的相互作用，以LD50/7和LD50/30为指标。这些值可能分别指示胃肠道干细胞耗竭和骨髓干细胞耗竭。当100 mg/kg的lucanthone非致死剂量先于CYC注射时，CYC的LD50/7在10小时的治疗间隔内达到最小值470 mg/kg。与CYC同时给药的lucanthone对750 mg/kg的对照LD50/7无影响，且在lucanthone给药后48小时，LD50/7已恢复到对照值。当CYC给药先于lucanthone时，LD50/7在5小时的时间间隔内达到最小值610 mg/kg；然而，对于整个序列，它在48小时内的所有时间间隔内大约为640 mg/kg。CYC的LD50/30仅因lucanthone的存在而略有降低，表明lucanthone对CYC的骨髓敏感性仅略有影响。这些数据表明，lucanthone可能与CYC损害以类似它与辐射损害相互作用的方式相互作用，即通过减少细胞积累和修复亚致死损伤的能力。

/LABORATORY ANIMALS: Acute Exposure/ The interaction of lucanthone and cyclophosphamide (CYC) was investigated in the Chinese hamster in terms of the LD50/7 and LD50/30. These values may be indicative of gastrointestinal stem cell depletion and bone marrow stem cell depletion, respectively. When a nonlethal dose of 100 mg/kg lucanthone preceded CYC injection, the LD50/7 for CYC reached its minimum value of 470 mg/kg at a treatment interval of 10 hours. Lucanthone administered simultaneously with CYC had no effect on the control LD50/7 of 750 mg/kg, and by 48 hours after lucanthone administration the LD50/7 had returned to the control value. When CYC administration preceded that of lucanthone, the LD50/7 reached a minimum of value of 610 mg/kg at an interval of 5 hours; however, for the entire sequence it was approximately 640 mg/kg over all intervals up to 48 hours. The LD50/30 for CYC was only slightly reduced by the presence of lucanthone, indicating that bone marrow sensitivity to CYC was only marginally affected by lucanthone. These data indicate that lucanthone may interact with CYC damage in much the same way as it interacts with radiation damage, viz, by reducing cellular capacity to accumulate and repair sublethal damage.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：亚慢性或预慢性暴露/给予中国仓鼠100毫克/千克的亚致死剂量的氯烷酮盐酸盐（Miracil D, Nilodin；NSC-14574）腹膜内注射（30天存活中位致死剂量（LD50/30）为315毫克/千克），降低了小肠对辐射的耐受性，对骨髓的辐射耐受性几乎没有影响。在整体60Co伽马辐射前后不同时间给予氯烷酮盐酸盐。7天存活中位致死剂量（LD50/7），表明死于胃肠道上皮剥脱，通过在辐射前10小时或辐射后7.5小时给予氯烷酮盐酸盐，从1235拉德降至最小值995拉德或985拉德。30天存活中位致死剂量（LD50/30），表明死于骨髓干细胞耗尽，在整个治疗过程中保持不变，大约为990拉德，这表明骨髓干细胞的辐射反应性不受氯烷酮盐酸盐的影响。氯烷酮盐酸盐的效果是可逆的，即在接种后40小时达到对照值LD50/7。通过分光光度法测定的中国仓鼠血清中氯烷酮盐酸盐的浓度，在接种后1.5小时达到峰值8微克/毫升，然后以大约6小时的半衰期指数下降，以至于在接种后30小时无法测量。

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ A sublethal dose of 100 mg lucanthone hydrochloride/kg (Miracil D, Nilodin; NSC-14574) administered ip into Chinese hamsters (median lethal dose for 30-day survival (LD50/30) of 315 mg/kg) reduced the radiation tolerance of the small intestine and had little or no effect on the radiation tolerance of the bone marrow. Lucanthone hydrochloride was administered at various times before and after whole-body 60Co gamma-irradiation. The median lethal dose for 7-day survival (LD50/7), indicative of death from gastrointestinal epithelial denudation, was reduced from 1,235 rads to minimum values of 995 rads or 985 rads by lucanthone hydrochloride inoculation 10 hours before irradiation or 7.5 hours post irradiation, respectively. The LD50/30, indicative of death from bone marrow stem cell depletion, remained unaltered at approximately 990 rads over the entire treatment scheme, which indicated that the radioresponsiveness of bone marrow stem cells was unaffected by lucanthone hydrochloride. The lucanthone hydrochloride effect was reversible in that control values of LD50/7 were attained by 40 hours post inoculation. Serum concentration of lucanthone hydrochloride in the Chinese hamster, determined spectrophotometrically, reached a peak of 8 microgram/ml by 1.5 hours post inoculation and then decreased exponentially with a half-life of approximately 6 hours, so that by 30 hours post inoculation it was unmeasurable.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...3H-露康酮在大鼠体内的器官分布以及125I-露康酮在小鼠体内的器官分布被确定，以了解露康酮是否能够穿越血脑屏障。通过磁共振成像或计算机断层扫描，对接受30 Gy全脑放疗单独治疗或联合露康酮治疗的患者的脑转移瘤的大小进行了测量。...在实验动物中，无论是腹腔注射还是静脉注射，露康酮在大脑中的分布时间过程与在肌肉和心脏中的分布时间过程相同。因此，露康酮在实验动物中容易穿越血脑屏障。...与单独放疗相比，接受露康酮和放疗的脑转移瘤患者的肿瘤消退速度加快，使用排列检验在p=0.0536的水平上接近显著性。

...The organ distribution of 3H lucanthone in mice and 125I lucanthone in rats was determined to learn if lucanthone crossed the blood-brain barrier. Size determinations were made of patients' brain metastases from magnetic resonance images or by computed tomography before and after treatment with 30 Gy whole brain radiation alone or with lucanthone. ...The time course of lucanthone's distribution in brain was identical to that in muscle and heart after intraperitoneal or intravenous administration in experimental animals. Lucanthone, therefore, readily crossed the blood-brain barrier in experimental animals. ...Compared with radiation alone, the tumor regression in patients with brain metastases treated with lucanthone and radiation was accelerated, approaching significance using a permutation test at p=0.0536.

来源:Hazardous Substances Data Bank (HSDB)

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] 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] ANTIFUNGAL COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS ANTI-FONGIQUES ET UTILISATIONS ASSOCIÉES
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2017143230A1

  公开（公告）日：2017-08-24

  Provided herein are compounds (e.g., compounds of Formulae (I), (II), and (III)) which are anti-fungal agents and can be used in the treatment of diseases, including infectious diseases. The invention provides methods of treating diseases in a subject (e.g., infectious diseases such as fungal infections), and methods of killing or inhibiting the growth of fungi in or on a subject or biological sample. The compounds may be used in subjects, in clinical settings, or in agricultural settings.

  本发明提供了化合物（例如，公式(I)、(II)和(III)的化合物），这些化合物是抗真菌剂，可用于治疗包括传染性疾病在内的疾病。本发明还提供了在主体（例如，真菌感染等传染性疾病）中治疗疾病的方法，以及杀死或抑制主体或生物样本内或上的真菌生长的方法。这些化合物可用于主体、临床环境或农业环境。
• [EN] PESTICIDAL AND PARASITICIDAL PYRAZOLE-ISOXAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS DE PYRAZOLE-ISOXAZOLINE À ACTIVITÉ PESTICIDE ET PARASITICIDE
  申请人：MERIAL INC

  公开号：WO2019036407A1

  公开（公告）日：2019-02-21

  The present invention relates to pesticidal and parasiticidal isoxazoline of formula (I) and salts thereof: wherein variables R1, P, Y and Q are described herein are as defined in the description. The invention also relates to parasiticidal and pesticidal compositions comprising the isoxazoline compounds of formula (I), 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)的杀虫剂和杀寄生虫的异恶唑啉及其盐：其中变量R1、P、Y和Q如本文所述，在描述中定义。本发明还涉及包含式(I)异恶唑啉化合物的杀寄生虫和杀虫组合物，其制备过程及其用于预防或治疗动物寄生虫感染或侵袭以及作为杀虫剂的应用。