3-{[(4-chlorobenzoxazol-2-yl)methyl]amino}-5-ethyl-6-methyl-2-(1H)-pyridinone | 139548-50-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 3-{[(4-chlorobenzoxazol-2-yl)methyl]amino}-5-ethyl-6-methyl-2-(1H)-pyridinone
• 英文别名: 2(1H)-Pyridinone, 3-(((4-chloro-2-benzoxazolyl)methyl)amino)-5-ethyl-6-methyl-；3-[(4-chloro-1,3-benzoxazol-2-yl)methylamino]-5-ethyl-6-methyl-1H-pyridin-2-one
• CAS: 139548-50-8
• 化学式: C₁₆H₁₆ClN₃O₂
• 分子量: 317.775
• InChiKey: BQAXJNKYEWRJGH-UHFFFAOYSA-N

物化性质

• 沸点：
  536.5±50.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

代谢

尽管锡金属的吸收非常差，但锡化合物可以通过口服、吸入或皮肤途径被吸收，有机锡化合物的吸收性比无机锡化合物要高得多。锡可能进入血液并绑定到血红蛋白上，在体内分布并主要在肾脏、肝脏、肺和骨骼中积累。锡及其代谢物主要通过尿液和粪便排出。硒可以通过吸入和摄入被吸收，而某些硒化合物也可能通过皮肤吸收。一旦进入体内，硒主要分布到肝脏和肾脏。硒是一种必需的微量元素，是谷胱甘肽过氧化物酶、碘甲状腺原氨酸5'-脱碘酶和硫氧还蛋白还原酶的组成部分。有机硒首先代谢为无机硒。无机硒逐步还原为中间体氢硒化物，然后转化为硒磷酸和硒半胱氨酸tRNA并整合到硒蛋白中，或者转化为硒化物的甲基化代谢物后排入尿液中。元素硒在排出前也会甲基化。硒主要通过尿液和粪便排出，但某些硒化合物也可能通过呼吸排出。(L619, L308)

Though tin metal is very poorly absorbed, tin compounds may be absorbed via oral, inhalation, or dermal routes, with organotin compounds being much more readily absorbed than inorganic tin compounds. Tin may enter the bloodstream and bind to hemoglobin, where it is distributed and accumulates mainly in the kidney, liver, lung, and bone. Tin and its metabolites are excreted mainly in the urine and feces. Selenium may be absorbed through inhalation and ingestion, while some selenium compounds may also be absorbed dermally. Once in the body, selenium is distributed mainly to the liver and kidney. Selenium is an essential micronutrient and is a component of glutathione peroxidase, iodothyronine 5'-deiodinases, and thioredoxin reductase. Organic selenium is first metabolized into inorganic selenium. Inorganic selenium is reduced stepwise to the intermediate hydrogen selenide, which is either incorporated into selenoproteins after being transformed to selenophosphate and selenocysteinyl tRNA or excreted into the urine after being transformed into methylated metabolites of selenide. Elemental selenium is also methylated before excretion. Selenium is primarily eliminated in the urine and feces, but certain selenium compounds may also be exhaled. (L619, L308)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

硒能够轻易地替代生物分子中的硫，并在许多生化反应中替代硫，特别是在硒的浓度高而硫的浓度低时。通过影响线粒体和微粒体的电子传递，使细胞呼吸中氧化反应所需的巯基酶失活，这可能是急性硒中毒的一个原因。硒代甲硫氨酸（一种常见的有机硒化合物）似乎也可以随机地替代蛋白质合成中的甲硫氨酸。这种替代可能会影响蛋白质的结构和功能性，例如，通过改变二硫键。无机形式的硒似乎通过氧化还原催化与组织巯基反应，产生反应性氧种，并通过氧化应激造成损害。无机和有机锡化合物是酒精脱氢酶的弱抑制剂。(A183, L619)

Selenium readily substitutes for sulfur in biomolecules and in many biochemical reactions, especially when the concentration of selenium is high and the concentration of sulfur is low. Inactivation of the sulfhydryl enzymes necessary for oxidative reactions in cellular respiration, through effects on mitochondrial and microsomal electron transport, might contribute to acute selenium toxicity. Selenomethionine (a common organic selenium compound) also appears to randomly substitute for methionine in protein synthesis. This substitution may affect the structure and functionability of the protein, for example, by altering disulfide bridges. Inorganic forms of selenium appear to react with tissue thiols by redox catalysis, resulting in formation of reactive oxygen species and causing damage by oxidative stress. Inorganic and organic tin compounds are weak inhibitors of alcohol dehydrogenase. (A183, L619)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

3, 其对人类致癌性无法分类。

3, not classifiable as to its carcinogenicity to humans. (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

摄入大量无机锡化合物可能会导致腹痛、贫血以及肝脏和肾脏问题。长期口腔暴露于高浓度的硒化合物可能会产生一种称为硒中毒的疾病。硒中毒的主要症状包括脱发、指甲变脆和神经异常（如四肢麻木和其他奇怪的感觉）。动物研究显示，硒也可能影响精子生产和女性的生殖周期。

Ingestion of large amounts of inorganic tin compounds can cause stomachache, anemia, and liver and kidney problems. Chronic oral exposure to high concentrations of selenium compounds can produce a disease called selenosis. The major signs of selenosis are hair loss, nail brittleness, and neurological abnormalities (such as numbness and other odd sensations in the extremities). Animal studies have shown that selenium may also affect sperm production and the female reproductive cycle. (L619, L307, L308)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服（L308）；吸入（L308）；皮肤给药（L308）

Oral (L308) ; inhalation (L308) ; dermal (L308)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

无机或有机锡化合物放置在皮肤或眼睛上可能引起皮肤和眼睛刺激。短期口服高浓度的硒可能导致恶心、呕吐和腹泻。短时间暴露于高浓度的元素硒或二氧化硒的空气中可能导致呼吸道刺激、支气管炎、呼吸困难以及胃痛。长期暴露于这两种空气传播形式可能导致呼吸道刺激、支气管痉挛和咳嗽。

Inorganic or organic tin compounds placed on the skin or in the eyes can produce skin and eye irritation. Short-term oral exposure to high concentrations of selenium may cause nausea, vomiting, and diarrhea. Brief exposures to high levels of elemental selenium or selenium dioxide in air can result in respiratory tract irritation, bronchitis, difficulty breathing, and stomach pains. Longer-term exposure to either of these air-borne forms can cause respiratory irritation, bronchial spasms, and coughing. (L619, L308)

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为产物：
  描述：

  2(1H)-吡啶酮,5-乙基-6-甲基-3-硝基- 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 20.0h， 生成 3-{[(4-chlorobenzoxazol-2-yl)methyl]amino}-5-ethyl-6-methyl-2-(1H)-pyridinone
  参考文献：
  名称：

  合成和评估2-吡啶酮衍生物作为HIV-1特异性逆转录酶抑制剂。2.3-氨基吡啶-2（1H）-1的类似物。

  摘要：

  合成了一系列非核苷3-氨基吡啶-2（1H）-一衍生物，并评估了其对HIV-1 RT的抑制作用。在使用rC.dG作为模板引物的酶分析中，几种类似物被证明是有效的高选择性拮抗剂，体外IC50值低至19 nM。该系列中的两种化合物，3-[[[（4,7-二甲基苯并恶唑-2-基）甲基]-氨基] -5-乙基-6-甲基吡啶2-2（1H）-一个（34，L-697,639）和相应的4,7-二氯类似物（37，L-697,661）在浓度为25-50 nM的MT4细胞培养物中可抑制HIV-1 IIIb感染的传播达95％，并被选作临床试验的抗病毒药。

  DOI：

  10.1021/jm00099a007

文献信息

• [EN] USE OF BHAP COMPOUNDS IN COMBINATION WITH OTHER NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS FOR THE TREATMENT OF HIV INFECTION<br/>[FR] UTILISATION DE COMPOSES BHAP EN COMBINAISON AVEC D'AUTRES INHIBITEURS DE LA TRANSCRIPTASE INVERSE NON-NUCLEOSIDIQUES DANS LE TRAITEMENT DES INFECTIONS A VIH
  申请人：THE UPJOHN COMPANY

  公开号：WO1994009781A1

  公开（公告）日：1994-05-11

  (EN) The present invention are methods of treating a HIV positive human which comprises (1) administering to the HIV positive individual a sensitizingly effective amount of a SENSITIZING HIV-1 INHIBITOR until increased sensitivity to a NON-NUCLEOSIDE HIV TREATMENT DRUG develops, (2) administering to the HIV positive individual an effective amount of a NON-NUCLEOSIDE HIV TREATMENT DRUG. An alternative method is a method of treating a HIV positive human which comprises administering to the HIV positive individual a sensitizingly effective amount of one or more SENSITIZING HIV-1 INHIBITOR concurrently with an effective amount of a NON-NUCLEOSIDE HIV TREATMENT DRUG.(FR) La présente invention se rapporte à des procédés de traitement d'un patient séropositif consistant à (1) administrer au patient séropositif une dose efficace sensibilisante d'un inhibiteur du VIH-1 sensibilisant jusqu'à ce qu'une sensibilité accrue à un médicament non-nucléosidique traitant le VIH se développe, (2) administrer au patient séropositif une dose efficace d'un médicament non-nucléosidique traitant le VIH. Une autre variante du procédé de traitement d'un patient séropositif consiste à administrer au patient séropositif une dose efficace sensibilisante d'un ou de plusieurs inhibiteurs du VIH sensibilisants, en même temps qu'une dose efficace d'un médicament non-nucléosidique traitant le VIH.

  本发明涉及治疗艾滋病毒（HIV）阳性人群的方法，包括：（1）向HIV阳性个体施用足够的敏感性HIV-1抑制剂，直到对非核苷类HIV治疗药物产生增加敏感性，（2）向HIV阳性个体施用足够的非核苷类HIV治疗药物。另一种方法是同时向HIV阳性个体施用足够的一种或多种敏感性HIV-1抑制剂和足够的非核苷类HIV治疗药物。
• Inhibitors of HIV reverse transcriptase
  申请人：MERCK & CO. INC.

  公开号：EP0462800A2

  公开（公告）日：1991-12-27

  Novel pyridones inhibit HIV reverse transcriptase, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by IV are also described.

  新型吡啶酮类药物可抑制艾滋病病毒逆转录酶，可用于预防或治疗艾滋病病毒感染和治疗艾滋病，可作为化合物、药学上可接受的盐、药物组合成分，无论是否与其他抗病毒药、抗感染药、免疫调节剂、抗生素或疫苗联合使用。还描述了治疗艾滋病的方法和预防或治疗 IV 感染的方法。
• Synergism of HIV reverse transcriptase inhibitors
  申请人：MERCK & CO. INC.

  公开号：EP0484071A2

  公开（公告）日：1992-05-06

  The combination of certain aminopyridones and anti-HIV nucleoside analogs has been found to synergistically inhibit HIV reverse transcriptase. This combination is useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as a combination of compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in further combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

  研究发现，某些氨基吡啶酮类药物和抗艾滋病毒核苷类似物的组合可协同抑制艾滋病毒逆转录酶。无论是否与其他抗病毒药、抗感染药、免疫调节剂、抗生素或疫苗进一步组合，这种组合物均可作为化合物、药学上可接受的盐、药物组合成分的组合物，用于预防或治疗艾滋病病毒感染和治疗艾滋病。还描述了治疗艾滋病的方法和预防或治疗艾滋病毒感染的方法。
• Recombinant human HIV-neutralizing monoclonal antibodies for prevention and treatment of HIV infection
  申请人：MERCK & CO. INC.

  公开号：EP0577243A2

  公开（公告）日：1994-01-05

  Recombinant human immunoglobulin molecules neutralizing for HIV-1, methods of production of the immunoglobulins and methods of preventing HIV-1 infection using the immunoglobulins are disclosed. DNA constructs containing the complementarity determining regions (CDRs) and framework (FRs) of the native human antibody are combined with other constant regions, and expressed in recombinant host cells. These recombinant antibodies are useful for the treatment and prevention of HIV-1 infection in vivo.

  本研究公开了中和 HIV-1 的重组人免疫球蛋白分子、免疫球蛋白的生产方法以及使用免疫球蛋白预防 HIV-1 感染的方法。含有原生人类抗体互补决定区（CDR）和框架（FR）的 DNA 构建体与其他恒定区结合，并在重组宿主细胞中表达。这些重组抗体可用于治疗和预防体内 HIV-1 感染。
• ANTIVIRAL COMBINATIONS
  申请人：GLAXO GROUP LIMITED

  公开号：EP0650362A1

  公开（公告）日：1995-05-03