杀螺胺乙醇胺盐 | 1420-04-8

• 物质功能分类: 化学农药原药 - 杀虫剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 杀螺胺乙醇胺盐
• 中文别名: 螺灭杀；N-(2-氯-4-硝基苯基)-2-羟基-5-氯苯甲酰乙醇胺；N-(2-氯-4-硝基苯基)-2-羟基-5-氯苯甲酰胺乙醇胺盐；5-氯水杨酸+2-氯-4-硝基苯胺；氯硝柳胺乙醇胺盐；贝螺杀
• 英文名称: N-(2-chloro-4-nitrophenyl)-2-hydroxy-5-chlorobenzamide ethanolamine salt
• 英文别名: niclosamide ethanolamine salt；niclosamide ethanolamine；niclosamide-ethanolamine；niclosamideethanolamine；niclosamide；NEN；4-Chloro-2-[(2-chloro-4-nitrophenyl)carbamoyl]phenolate;2-hydroxyethylazanium
• CAS: 1420-04-8
• 化学式: C₂H₇NO*C₁₃H₈Cl₂N₂O₄
• 分子量: 388.207
• InChiKey: XYCDHXSQODHSLG-UHFFFAOYSA-N

物化性质

• 熔点：
  204°
• 溶解度：
  DMF：30mg/mL；二甲基亚砜：30mg/mL； DMSO:PBS (pH 7.2) (1:1)：0.5 mg/mL；乙醇：0.25mg/mL
• 物理描述：
  Clonitralid is a yellow solid. Insoluble in water. (NTP, 1992)
• 颜色/状态：
  BRIGHT YELLOW, CRYSTALLINE
• 蒸汽压力：
  <1X10-7 mbar @ 20 °C (7.5X10-8 mm Hg)
• 稳定性/保质期：

  如果遵照规格使用和储存，则不会分解，未有已知危险反应。请避免与氧化物接触。

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  6

ADMET

代谢

糖苷酸结合已经在暴露于克洛尼特罗莱德的虹鳟鱼中展现。

GLUCURONIDE CONJUGATION HAS BEEN EXHIBITED IN RAINBOW TROUT EXPOSED TO CLONITRALIDE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：尼可洛刹米在美国没有上市。没有关于在哺乳期间使用尼可洛刹米的临床信息。由于尼可洛刹米不被口服吸收，因此不太可能对哺乳婴儿产生不利影响。不需要特别的预防措施。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Niclosamide is not marketed in the United States. No information is available on the clinical use of niclosamide during breastfeeding. Because niclosamide is not orally absorbed it is unlikely to adversely affect the breastfed infant. No special precautions are necessary. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

3-三氟甲基-4-硝基苯酚或3-三氟甲基-4-硝基苯酚与克洛尼曲拉德的组合使用会导致一些寡毛纲动物、水蛭、蜉蝣的不成熟形态以及某些毛翅目、摇蚊科和两栖动物的死亡。3-三氟甲基-4-硝基苯酚与克洛尼曲拉德的组合可能会影响一些腹足纲和软体动物，但其对无脊椎动物的整体影响可能小于单独使用3-三氟甲基-4-硝基苯酚。颗粒状的克洛尼曲拉德可能会引起寡毛纲动物、小型甲壳类、摇蚊和腹足纲动物的死亡。没有证据表明杀鲑剂导致了任何物种的灾难性下降或消失。与捕杀海鳗带来的益处相比，化学控制海鳗对水生群落的影响总体上是较小的。

THE CHEMICALS 3-TRIFLUOROMETHYL-4-NITROPHENOL OR A COMBINATION OF 3-TRIFLUOROMETHYL-4-NITROPHENOL & CLONITRALIDE CAUSE SOME MORTALITIES OF OLIGOCHAETA & HIRUDINEA, IMMATURE FORMS OF EPHEMEROPTERA, & CERTAIN TRICHOPTERA, SIMULIIDAE, & AMPHIBIA. THE COMBINATION OF 3-TRIFLUOROMETHYL-4-NITROPHENOL & CLONITRALIDE MAY AFFECT SOME PELECYPODA & GASTROPODS, BUT ITS OVERALL EFFECTS ON INVERTEBRATES ARE PROBABLY LESS THAN THOSE OF 3-TRIFLUOROMETHYL-4-NITROPHENOL ALONE. GRANULAR CLONITRALIDE IS LIKELY TO INDUCE MORTALITIES AMONG OLIGOCHAETES, MICROCRUSTACEANS, CHIRONOMIDS, & PELECYPODS. NO EVIDENCE EXISTS THAT THE LAMPRICIDES HAVE CAUSED THE CATASTROPHIC DECLINE OR DISAPPEARANCE OF ANY SPECIES. THE OVERALL IMPACT OF CHEMICAL CONTROL OF SEA LAMPREYS ON AQUATIC COMMUNITIES HAS BEEN MINOR COMPARED WITH THE BENEFITS DERIVED.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

24小时涂抹于人类皮肤上未引起刺激性。

... 24 HR APPLICATION TO HUMAN SKIN CAUSED NO IRRITATION.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

在大鼠身上进行的长期喂养研究（将1%至2.5%的测试物质添加到标准食物中，每周5次，持续326至219天）和狗（每周5次，每次0.1克/千克，通过明胶胶囊给药，持续1年）在实验期间未出现中毒症状，并且在实验结束时解剖时也未发现病理变化。

CHRONIC FEEDING STUDIES ON RATS (1% ... 2.5% ADDED TO STANDARD FOOD 5 TIMES WEEKLY FOR 326 ... 219 DAYS /RESPECTIVELY/) & DOGS (0.1 G/KG APPLIED 5 TIMES WEEKLY IN GELATINE CAPSULES DURING 1 YR) SHOWED NO POISONING SYMPTOMS DURING COURSE OF EXPERIMENT & NO PATHOLOGICAL CHANGES WHEN DISSECTED @ END OF EXPERIMENT.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

它是非植物毒性的，在田间的浓度。

IT IS NON-PHYTOTOXIC @ FIELD CONCN.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

无脊椎动物暴露于14C-杀螺菌素（1微克/升）时，全身残留量较低。在48小时内，无脊椎动物（水蚤、潮虫、水黾、玻璃虾、小龙虾、蜻蜓幼虫和摇蚊幼虫）的残留量达到平台期，这些平台期的残留量是它们暴露浓度的4到87倍。当这些生物转移到清水中后，24小时内这些残留量减少了50%。

WHOLE BODY RESIDUES WERE LOW IN INVERTEBRATES EXPOSED TO (14)C-BAYLUSCIDE (1 UG/L). WITHIN 48 HR, INVERTEBRATES (DAPHNIDS, SOWBUGS, SCUDS, GLASS SHRIMP, CRAYFISH, DAMSELFLY LARVAE, AND MIDGE LARVAE) REACHED PLATEAUS WHICH WERE 4 TO 87 TIMES THAT OF THE CONCN TO WHICH THEY WERE EXPOSED. A 50% REDUCTION IN THESE RESIDUES OCCURRED WITHIN 24 HR AFTER THE ORGANISMS WERE TRANSFERRED TO FRESH WATER.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

克洛尼特拉lide的残留物被暴露于杀鳗剂的鱼迅速积累。在暴露期间，肌肉残留水平增加到接近处理浓度。撤回10天后，虹鳟鱼和银大麻哈鱼的血浆、胆汁和肌肉中的残留物降至各自峰值的1%以下。在所有测试的物种中，肌肉中的残留物在3-14天内降至检测限以下（0.01微克/克）。在早期撤回期间最初增加之后，胆汁残留物稳步下降，但在14天内渠道鲶鱼中没有降至初始水平以下，或者在撤回28天后银大麻哈鱼中没有降至检测水平以下（0.01微克/毫升）。

RESIDUES OF CLONITRALIDE WERE RAPIDLY ACCUMULATED BY FISH EXPOSED TO THE LAMPRICIDE. MUSCLE RESIDUE LEVELS INCREASED TO NEAR THE TREATMENT CONCN DURING EXPOSURE. AFTER 10 DAYS OF WITHDRAWAL, RESIDUES IN PLASMA, BILE, & MUSCLE OF RAINBOW TROUT & COHO SALMON DECREASED TO LESS THAN 1% OF THEIR RESPECTIVE PEAK CONCN. IN ALL SPECIES TESTED, RESIDUES IN MUSCLE DROPPED BELOW THE LIMIT OF DETECTION (0.01 UG/G) WITHIN 3-14 DAYS. AFTER AN INITIAL INCREASE DURING EARLY WITHDRAWAL, BILE RESIDUES DECLINED STEADILY BUT HAD NOT DROPPED BELOW INITIAL LEVELS IN CHANNEL CATFISH IN 14 DAYS, OR BELOW DETECTABLE LEVELS (0.01 UG/ML) IN COHO SALMON AFTER 28 DAYS OF WITHDRAWAL.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

水中的虹鳟鱼接触到克洛尼特莱德后，很快就开始在尿液中排出结合态和自由态的克洛尼特莱德，其中在12小时暴露期间排出的量最大。即使在暴露后60小时，虹鳟鱼仍在排出克洛尼特莱德。排出的结合态克洛尼特莱德是自由态的15倍。在接受腹腔注射的鱼类中，注射剂量的25%在尿液中提取，20%在胆汁中恢复。克洛尼特莱德的暴露对尿量或肾排出钠、钾、钙或氯离子的排泄没有影响。

RAINBOW TROUT EXPOSED TO CLONITRALIDE IN THE WATER QUICKLY BEGAN TO EXCRETE CONJUGATED & FREE CLONITRALIDE IN THE URINE, WITH THE LARGEST AMOUNT BEING EXCRETED DURING THE 12 HR EXPOSURE. THE TROUT CONTINUED TO EXCRETE CLONITRALIDE 60 HR AFTER EXPOSURE. FIFTEEN TIMES AS MUCH CONJUGATED AS FREE CLONITRALIDE WAS EXCRETED. AMONG FISH GIVEN IP INJECTIONS, 25% OF THE INJECTED DOSE WAS EXTRACTED IN THE URINE, & 20% RECOVERY IN THE BILE. CLONITRALIDE EXPOSURE HAD NO EFFECT ON THE URINE OUTPUT OR RENAL EXCRETION OF SODIUM, POTASSIUM, CALCIUM, OR CHLORIDE IONS.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品运输编号：
  UN 1325 4.1/PG 2
• WGK Germany：
  3
• 危险类别：
  4.1
• 安全说明：
  S16,S26,S36/37/39,S45
• 包装等级：
  III
• 储存条件：
  请将贮藏器密封，并存放在阴凉、干燥处。确保工作环境有良好的通风或排气设施。

制备方法与用途

简介

杀螺胺是世卫组织推荐的一种用于防治水稻福寿螺的高效产品，对环境和人类友好安全。虽然杀螺胺难溶于水，但通过将其制成乙醇胺盐形式，在20摄氏度时其水溶解度可提高至每升0.1克，从而减轻了对眼睛和皮肤的刺激性。

生物活性

Niclosamide olamine（BAY2353 olamine）是一种驱虫剂，能够破坏寄生虫及动物模型中线粒体的代谢过程。这种化合物能够可逆地抑制雷帕霉素复合物 (mTORC1) 的哺乳动物靶标，并通过将IC50值降至0.25 μM来抑制STAT3，进而促进自噬反应。

用途

可用于防治福寿螺等害虫。

文献信息

• [EN] NOVEL MITOCHONDRIAL UNCOUPLERS FOR TREATMENT OF METABOLIC DISEASES AND CANCER<br/>[FR] NOUVEAUX DÉCOUPLANTS MITOCHONDRIAUX POUR LE TRAITEMENT DE MALADIES MÉTABOLIQUES ET DU CANCER
  申请人：JIN SHENGKAN

  公开号：WO2017201313A1

  公开（公告）日：2017-11-23

  The present disclosure relates to benzamide compounds, prodrugs of the compounds, pharmaceutical compositions containing the compounds and/or the prodrugs and methods of using the compounds, prodrugs and pharmaceutical compositions in the treatment of diseases related to lipid metabolism including diabetes, Non-Alcholic Fatty Liver Disease (NAFLD), Non-Alcholic Steathohepatitis (NASH), diseases caused by abnormal cell proliferation including cancer, psoriasis, and infectious diseases.

  本公开涉及苯甲酰胺化合物、该化合物的前体药物、含有该化合物和/或前体药物的药物组合物，以及使用这些化合物、前体药物和药物组合物治疗与脂质代谢相关的疾病，包括糖尿病、非酒精性脂肪肝病（NAFLD）、非酒精性脂肪性肝炎（NASH）、由异常细胞增殖引起的疾病，包括癌症、牛皮癣和传染病的方法。
• NICOTINYL RIBOSIDE COMPOUNDS AND THEIR USES
  申请人：MitoPower, LLC

  公开号：US20200397807A1

  公开（公告）日：2020-12-24

  The disclosure provides nicotinamide riboside (NR), the reduced form of NR (NRH), nicotinic acid riboside (NAR), the reduced form of NAR (NARH), derivatives thereof, compositions thereof and uses thereof. The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR. NR, NRH, NAR, NARH, and derivatives thereof can increase cellular NAD + levels and enhance mitochondrial and cellular function and cell viability. Therefore, NR, NRH, NAR, NARH, and derivatives thereof, whether alone or in combination with one or more additional therapeutic agents (e.g., a mitochondrial uncoupler or/and a PARP inhibitor), are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, metabolic disorders, and other disorders and conditions.

  该披露提供烟酰胺核糖苷（NR）、烟酰胺核糖苷的还原形式（NRH）、烟酸核糖苷（NAR）、烟酸核糖苷的还原形式（NARH）、以及它们的衍生物、组合物和用途。与NR和NAR相比，NR和NAR的衍生物具有更好的稳定性和生物利用度。NR、NRH、NAR、NARH和它们的衍生物可以增加细胞NAD+水平，增强线粒体和细胞功能以及细胞存活能力。因此，NR、NRH、NAR、NARH和它们的衍生物，无论是单独使用还是与一个或多个额外治疗剂（例如线粒体解耦蛋白抑制剂和/或PARP抑制剂）结合使用，都可用于治疗线粒体疾病、与线粒体相关的疾病和症状、代谢紊乱以及其他疾病和症状。
• PD-1 SIGNAL INHIBITOR COMBINATION THERAPY
  申请人：Kyoto University

  公开号：EP3388084A1

  公开（公告）日：2018-10-17

  A novel therapeutic strategy for the anti-PD-1 antibody therapy is provided. A pharmaceutical composition which comprises at least one substance selected from the group consisting of the following (i) to (iii) and is administered before, after or simultaneously with the administration of a PD-1 signal inhibitor: (i) ROS generators and substances that regulate downstream signaling pathways thereof, (ii) substances exhibiting an uncoupling effect and substances that regulate downstream signaling pathways thereof, and (iii) amino acids.

  本研究提供了一种新型的抗PD-1抗体治疗策略。 一种药物组合物，它包含至少一种选自以下(i)至(iii)组的物质，并在给药 PD-1 信号抑制剂之前、之后或同时给药： (i) ROS 生成物和调节其下游信号通路的物质、 (ii) 具有解偶联效应的物质和调节其下游信号通路的物质，以及 (iii) 氨基酸。
• COMPOUND FOR USE IN THE TREATMENT OF A DISEASE CHARACTERIZED BY DYSREGULATED MUCUS PRODUCTION AND/OR SECRETION
  申请人：Universität Regensburg

  公开号：EP3639822A1

  公开（公告）日：2020-04-22

  The present invention relates to a compound for use in a method of treating a disease selected from cystic fibrosis, ulcerative colitis, and irritable bowel syndrome, wherein said compound is an inhibitor of a TMEM16 protein, preferably of TMEM16A and/or TMEM16F.

  本发明涉及一种用于治疗选自囊性纤维化、溃疡性结肠炎和肠易激综合征的疾病的方法的化合物，其中所述化合物是TMEM16蛋白的抑制剂，优选TMEM16A和/或TMEM16F的抑制剂。
• Mitochondrial uncouplers for treatment of metabolic diseases and cancer
  申请人：RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY

  公开号：US10227315B2

  公开（公告）日：2019-03-12

  The present disclosure relates to benzamide compounds, prodrugs of the compounds, pharmaceutical compositions containing the compounds and/or the prodrugs and methods of using the compounds, prodrugs and pharmaceutical compositions in the treatment of diseases related to lipid metabolism including diabetes, Non-Alcholic Fatty Liver Disease (NAFLD), Non-Alcholic Steathohepatitis (NASH), diseases caused by abnormal cell proliferation including cancer, psoriasis, and infectious diseases.

  本公开涉及苯甲酰胺化合物、该化合物的原药、含有该化合物和/或原药的药物组合物以及使用该化合物、原药和药物组合物治疗与脂质代谢有关的疾病（包括糖尿病、非胆汁性脂肪肝（NAFLD）、非胆汁性脂肪性肝炎（NASH））、由细胞异常增殖引起的疾病（包括癌症、牛皮癣和传染性疾病）的方法。