硝羟四氢喹啉胺 | 21738-42-1

• 物质功能分类: 原料药 - 抗寄生虫病药 - 抗吸虫病药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 硝羟四氢喹啉胺
• 中文别名: 羟氨喹
• 英文名称: oxaminiquine
• 英文别名: Oxamniquine；dl-6-hydroxymethyl-2-isopropylaminomethyl-7-nitro-1,2,3,4-tetrahydroquinoline；[7-nitro-2-[(propan-2-ylamino)methyl]-1,2,3,4-tetrahydroquinolin-6-yl]methanol
• CAS: 21738-42-1
• 化学式: C₁₄H₂₁N₃O₃
• 分子量: 279.339
• InChiKey: XCGYUJZMCCFSRP-UHFFFAOYSA-N

物化性质

• 熔点：
  147-149°
• 沸点：
  422.1°C (rough estimate)
• 密度：
  1.1119 (rough estimate)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• 物理描述：
  Solid
• 颜色/状态：
  Pale yellow crystals from isopropanol

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  90.1
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

代谢

很可能是肝脏的

Probably hepatic

来源:DrugBank

代谢

药物被广泛代谢，主要在胃肠道粘膜和/或腔内通过酶促氧化将6-羟甲基基团转化为6-羧酸代谢物。在尿液中也观察到了微量的2-羧酸代谢物，这反映了侧链的氧化。这些代谢物不具有抗血吸虫活性。

The drug is extensively metabolized, principally in the GI mucosa and/or lumen via enzymatic oxidation of the 6-hydroxymethyl group to the 6-carboxylic acid metabolite. Trace amounts of the 2-carboxylic acid metabolite have also been observed in urine, which reflects oxidation of the side chain. These metabolites do not possess antichistosomal activity.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

一项来自小鼠研究的有限证据表明，当同时给予奥克曼喹和吡喹酮时，这两种药物对曼氏血吸虫的抗血吸虫活性可能具有协同作用。

Limited evidence from one study in mice indicates that the antischistosomal activity of oxamniquine and praziquantel may be synergistic against Schistosoma mansoni when the two drugs are administered concomitantly.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

药物在食物存在的情况下的胃吸收速率和程度都会降低。

The rate and extent of GI absorption of the drug are decreased by the presence of food.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

神经系统影响在奥克曼喹治疗中经常发生；然而，这些影响大多数都是轻微且短暂的。奥克曼喹最常见的不良反应是头晕、嗜睡和头痛，大约30-50%接受药物的患者会出现这些症状。其他较少见的神经系统不良反应...包括行为改变、兴奋、幻觉或现实扭曲。失眠、不适和可逆性遗忘症报告罕见。偶尔会有患者的脑电图异常...全身性癫痫，通常发生在最初的几小时内...并且通常与脑电图改变有关，接受药物治疗的患者中罕见观察到，特别是在有癫痫病史的患者中。

Nervous system effects occur frequently with oxamniquine; however, most of these effects are mild and transient. The most frequent adverse effects of oxamniquine are dizziness, drowsiness, and headache, which occur in about 30-50% of patients receiving the drug. Other less frequent adverse nervous effects ... include behavioral changes, excitation, and hallucinations or distortion of reality. Insomnia, malaise, and reversible amnesia have been reported rarely. EEG abnormalities occur occasionally in patients. ... Generalized seizures, which usually occur within the first few hours ... and generally are associated with EEG changes, have been observed rarely in patients receiving the drug, particularly in those with a history of seizure disorders.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

奥克曼喹的GI（胃肠道）副作用比常见的神经系统副作用发生频率低，包括恶心、呕吐、腹痛、厌食和腹泻。

GI effects of oxamniquine, which occur less frequently than common nervous system effects, include nausea, vomiting, abdominal pain, anorexia and diarrhea.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

荨麻疹、皮疹、瘙痒和关节痛在一些接受奥克曼喹治疗的病人中有所报告。发热，在奥克曼喹给药后1-5天出现，持续2-5天然后退热，在主要在埃及接受该药物治疗血吸虫病的患者中有所报告；据报道，健康、未感染的成年人在静脉注射该药物后并未出现发热。极少数患者出现了轻微、非特异性的心电图变化和肺部放射学变化，主要表现为肺部致密影。

Urticaria, rash, pruritus, and joint pain have been reported in some patients receiving oxamniquine. Fever, which occurs 1-5 days after administration of oxamniquine and persists for 2-5 days before defervescence, has been reported in patients receiving the drug for treatment of schistosomiasis principally in Egypt; fever reportedly has not occurred following im administration of the drug to healthy, uninfected adults. Minor, nonspecific ECG changes and pulmonary radiographic changes, principally characterized by pulmonary condensations have occurred in a few patients.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

口服吸收良好

Well absorbed orally

来源:DrugBank

吸收、分配和排泄

奥克西玛尼及其代谢物主要通过尿液排泄。大约40-75%的口服剂量在给药后24小时内以6-羧酸代谢物的形式通过尿液排出。大约0.5-2%的口服剂量以原型药的形式通过尿液排出；不到1%的剂量以2-羧酸代谢物的形式通过尿液排出。

Oxamniquine and its metabolites are excreted mainly in urine. Approximately 40-75% of an oral dose of the drug is excreted in urine within 24 hours of administration, principally as the 6-carboxylic acid metabolite. About 0.5-2% of an oral dose is excreted in urine unchanged; less than 1% of a dose is excreted in urine as the 2-carboxylic acid metabolite.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

奥克曼喹在口服给药后吸收良好。食物的存在会降低药物在胃肠道的吸收速率和程度。在口服常规剂量后，大约1-3小时达到奥克曼喹的血浆峰值浓度。 ... 患者之间血浆奥克曼喹浓度的差异可能是由于药物在胃肠道粘膜吸收过程中发生生物降解所致。 ... 奥克曼喹在动物体内胃肠道腔内以及在吸收过程中通过胃肠道粘膜广泛进行首次通过代谢。

Oxamniquine is well absorbed following oral administration. The rate and extent of GI absorption of the drug are decreased by the presence of food. Peak plasma concentrations of oxamniquine occur approximately 1-3 hours after oral administration of usual doses of the drug. ... Interpatient variation in plasma oxamniquine concentrations may result from biodegradation of the drug in the GI mucosa during absorption. ... Oxamniquine undergoes extensive first pass metabolism in the GI lumen before absorption and/or in the GI mucosa during absorption in animals.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一项研究中，成人和儿童单一口服15毫克/公斤剂量的奥克曼喹后，血药浓度峰值在70-2595和89-1500纳克/毫升之间，分别在1.5-3小时出现。在另一项研究中，晚期肝脾血吸虫病患者和健康成人单一口服1克剂量的奥克曼喹后，平均血药浓度峰值分别为大约1.7小时时的1267纳克/毫升和大约1.4小时时的1983纳克/毫升。

Following oral administration of a single 15 mg/kg dose of oxamniquine in adults and children with Schistosoma mansoni infection in one study, peak serum drug concentrations of 70-2595 and 89-1500 ng/ml, respectively, occurred at 1.5-3 hours. In another study, following oral administration of a single 1 g dose of oxamniquine in patients with advaced hepatosplenic schistosomiasis and in healthy adults, mean peak plasma drug concentrations of 1267 ng/ml at about 1.7 hours and 1983 ng/ml at about 1.4 hours occurred, respectively.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2933499090

制备方法与用途

生物活性

Oxamniquine 是一种有效的抗血吸虫病试剂。

靶点

Parasite

体外研究

Oxamniquine 是治疗血吸虫病的强效剂。

体内研究

单独使用 Oxamniquine (500 mg/kg) 或与普拉奎宁 (250 mg/kg) 联合使用，均可减少感染螺蛳的死亡率，相较于对照组更为显著。

反应信息

• 作为反应物：
  描述：

  硝羟四氢喹啉胺 在 manganese(IV) oxide 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N²-<(2-nitrophenyl)thio>oxamniquine
  参考文献：
  名称：

  Studies on some derivatives of oxamniquine

  摘要：

  On the basis of the remarkable biological similarities between hycanthone and oxamniquine and as a sequel to our finding that some esters of hycanthone are active against hycanthone-resistant schistosomes, we prepared oxamniquine acetate, oxamniquine N-methylcarbamate, and four substituted phenylsulfonohydrazones of oxamniquine aldehyde. These compounds were tested for their effect on survival of and on [3H]uridine incorporation into hycanthone-sensitive and -resistant Schistosoma mansoni. All of these derivatives were effective to a greater or lesser degree in killing worms and in inhibiting [3H]uridine incorporation in the sensitive strain, but none was effective in the resistant strain.

  DOI：

  10.1021/jm00403a024
• 作为产物：
  描述：

  oxamniquine aldehyde 、 硼氢化钠 生成 硝羟四氢喹啉胺
  参考文献：
  名称：

  EL-HAMOULY, WAGEEH;PICA-MATTOCCIA, LIVIA;CIOLI, DONATO;SCHWARTZ, HERBERT +, J. MED. CHEM., 31,(1988) N 8, 1629-1631

  摘要：

  DOI：

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] PRODRUGS OF SECONDARY AMINE COMPOUNDS<br/>[FR] PROMÉDICAMENTS DE COMPOSÉS AMINE SECONDAIRES
  申请人：ALKERMES PHARMA IRELAND LTD

  公开号：WO2013088255A1

  公开（公告）日：2013-06-20

  The present invention relates to compounds of Formula (I).

  本发明涉及式(I)的化合物。
• [EN] BIOREVERSABLE PROMOIETIES FOR NITROGEN-CONTAINING AND HYDROXYL-CONTAINING DRUGS<br/>[FR] PRO-FRAGMENTS BIORÉVERSIBLES POUR MÉDICAMENTS CONTENANT DE L'AZOTE ET DE L'HYDROXYLE
  申请人：BAIKANG SUZHOU CO LTD

  公开号：WO2015081891A1

  公开（公告）日：2015-06-11

  Disclosed are promoieties of the following formula which can be used to form prodrugs of nitrogen-containing or hydroxyl-containing drug or a pharmaceutically active agent: (I) and pharmaceutical compositions comprising the prodrugs.

  披露了以下公式的促销性质，它们可用于形成含有氮或羟基的药物或药物活性剂的的前药：(I)以及包含这些前药的药物组合物。
• [EN] BORON-CONTAINING SMALL MOLECULES AS ANTI-PROTOZOAL AGENT<br/>[FR] PETITES MOLÉCULES BORÉES EN TANT QU'AGENT ANTI-PROTOZOAIRE
  申请人：ANACOR PHARMACEUTICALS INC

  公开号：WO2011116348A1

  公开（公告）日：2011-09-22

  This invention provides, among other things, novel compounds useful for treating protozoal infections, pharmaceutical compositions containing such compounds, as well as combinations of these compounds with at least one additional therapeutically effective agent. The compounds are of the formula, wherein Y' is a halogen, Y is halosubstituted alkyl, or a salt thereof.

  这项发明提供了用于治疗原虫感染的新型化合物，含有这些化合物的药物组合物，以及这些化合物与至少一种额外治疗有效药剂的组合物。这些化合物的化学式为，其中Y'是卤素，Y是卤代烷基，或其盐。