占托西林 | 580-74-5

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 中文名称: 占托西林
• 中文别名: 黄青霉素；青黴黃素X；青黄霉素
• 英文名称: xanthocillin X
• 英文别名: xanthocillin；Xantocillin；4-[(1Z,3Z)-4-(4-hydroxyphenyl)-2,3-diisocyanobuta-1,3-dienyl]phenol
• CAS: 580-74-5；11042-38-9
• 化学式: C₁₈H₁₂N₂O₂
• 分子量: 288.305
• InChiKey: YBMVKDUTYAGKEW-WHYMJUELSA-N

物化性质

• 沸点：
  430.53°C (rough estimate)
• 密度：
  1.2396 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.2
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

代谢

氰化物通过口服、吸入和皮肤途径迅速被吸收，并分布到全身。氰化物主要通过罗丹酶或3-巯基丙酸硫转移酶代谢成硫氰化物。氰化物的代谢物通过尿液排出。

Cyanide is rapidly alsorbed through oral, inhalation, and dermal routes and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

氰化物是电子传递链第四个复合体中细胞色素c氧化酶的抑制剂（存在于真核细胞线粒体膜中）。它与这种酶中的铁原子形成复合物。氰化物与这种细胞色素的结合阻止了电子从细胞色素c氧化酶传递到氧气。结果，电子传递链被中断，细胞无法再通过有氧呼吸产生ATP能量。主要依赖有氧呼吸的组织，如中枢神经系统和心脏，受到特别影响。氰化物也通过绑定过氧化氢酶、谷胱甘肽过氧化物酶、变性血红蛋白、羟钴胺素、磷酸酶、酪氨酸酶、抗坏血酸氧化酶、黄嘌呤氧化酶、琥珀酸脱氢酶和Cu/Zn超氧化物歧化酶来产生一些毒性效应。氰化物与变性血红蛋白中的铁离子结合形成无活性的氰化变性血红蛋白。（L97）

Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

短时间内接触高浓度的氰化物会损害大脑和心脏，甚至可能导致昏迷、癫痫、呼吸暂停、心脏骤停和死亡。长期吸入氰化物会引起呼吸困难、胸痛、呕吐、血象改变、头痛和甲状腺肿大。皮肤接触氰化物盐可能会刺激并产生溃疡。

Exposure to high levels of cyanide for a short time harms the brain and heart and can even cause coma, seizures, apnea, cardiac arrest and death. Chronic inhalation of cyanide causes breathing difficulties, chest pain, vomiting, blood changes, headaches, and enlargement of the thyroid gland. Skin contact with cyanide salts can irritate and produce sores. (L96, L97)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服（L96）；吸入（L96）；皮肤给药（L96）

Oral (L96) ; inhalation (L96) ; dermal (L96)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

氰化物中毒的表现包括快速、深大的呼吸和呼吸急促，全身无力，眩晕，头痛，头晕，混乱，抽搐/癫痫发作，最终失去意识。

Cyanide poisoning is identified by rapid, deep breathing and shortness of breath, general weakness, giddiness, headaches, vertigo, confusion, convulsions/seizures and eventually loss of consciousness. (L96, L97)

来源:Toxin and Toxin Target Database (T3DB)

制备方法与用途

生物活性

Xanthocillin 是从青霉中提取的一种海洋药剂，通过抑制 MEK/ERK 途径诱导自噬。

体外研究

• 细胞增殖实验
  Xantocillin (SD118-xanthocillin X (1)) 在6.9至55.56 µM浓度下作用48小时后，显著抑制了HepG2细胞的增殖。其半数抑制浓度（IC₅₀）为22.88 ± 4.76 µM。

• 自噬相关基因表达
  Xantocillin (SD118-xanthocillin X (1)) 在24.3 µM浓度下作用12至48小时后，增加了与自噬相关的基因LC3和Beclin 1的表达。

实验数据

• 细胞增殖实验

  • 细胞系：HepG2细胞
  • 浓度：6.9 µM、13.89 µM、27.78 µM、55.56 µM
  • 培养时间：48小时
  • 结果：浓度依赖性地抑制HepG2细胞的增殖，半数抑制浓度（IC₅₀）为22.88 ± 4.76 µM。

• Western Blot 分析

  • 细胞系：HepG2细胞
  • 浓度：24.3 µM
  • 培养时间：12小时、24小时、48小时
  • 结果：增加了与自噬相关的基因LC3和Beclin 1的表达。

反应信息

• 作为反应物：
  描述：

  占托西林 在 甲醇 、 sodium acetate 、 镍 作用下， 生成 2,3-bis-(4-acetoxy-benzyl)-pyrazine
  参考文献：
  名称：

  Hagedorn; Toenjes, Pharmazie, 1957, vol. 12, p. 567,576

  摘要：

  DOI：
• 作为产物：
  描述：

  (1Z,3Z)-2,3-diisocyano-1,4-bis(4-tert-butyldimethylsilyloxyphenyl)buta-1,3-diene 在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以85%的产率得到占托西林
  参考文献：
  名称：

  ALPHA-SUBSTITUTED VINYLTIN COMPOUND

  摘要：

  提供α-取代的乙烯基锡，用于寻找功能发展物质，如药物/农药和功能材料，以及用于构建化合物库。由下式表示的α-取代的乙烯基锡化合物（1）或其互变异构体或盐或溶剂合物：R2CH═C(R3)Sn(R1)3（1）其中R1是C1-10烷基，C2-14芳基或类似物，R2是C2-14芳基，C2-9杂环基，C3-10环烷基或类似物，R3是氨基甲酰基，硫氨基甲酰基，异氰酸酯基，异硫氰酸酯基，甲酰氨基基，硫代甲酰氨基基，异腈基，脲基，氨基甲酸酯基或类似物。

  公开号：

  US20090023939A1

文献信息

• FORMYLATED XANTHOCILLIN ANALOGUES AS NEUROPROTECTIVE AGENTS
  申请人：NEURON BIOPHARMA, S.A.

  公开号：US20150011621A1

  公开（公告）日：2015-01-08

  Formylated xanthocillin analogs can be used in the treatment of neurodegenerative diseases. The analogs can be prepared synthetically, and at least some of the analogs can be obtained from a microorganism strain of the Penicillium chrysogenum species.

  甲酰化黄色素类似物可用于治疗神经退行性疾病。这些类似物可以通过合成制备，至少其中一些类似物可以从青霉属(Penicillium chrysogenum)微生物菌株中获得。
• α-Substituted vinyltin compound
  申请人：Nissan Chemical Industries, Ltd.

  公开号：US07595415B2

  公开（公告）日：2009-09-29

  To provide α-substituted vinyltin useful for the search for function-developing substances such as pharmaceuticals/agrichemicals and functional materials and for the construction of a compound library. An α-substituted vinyltin compound represented by the formula (1), a tautomer or salt of the compound or a solvate thereof: R2CH═C(R3)Sn(R1)3  (1) wherein R1 is a C1-10 alkyl group, a C2-14 aryl group or the like, R2 is a C2-14 aryl group, a C2-9 heterocyclyl group, a C3-10 cycloalkyl group or the like, and R3 is a carbamoyl group, a thiocarbamoyl group, an isocyanate group, an isothiocyanate group, a formylamino group, a thioformylamino group, an isonitrile group, an urea group, a carbamate group or the like.

  为了提供α-取代乙烯基锡，用于寻找功能发展物质如制药/农业化学品和功能材料以及构建化合物库。α-取代乙烯基锡化合物由以下式子表示（1），其互变异构体或盐或其溶剂化物： R2CH═C(R3)Sn(R1)3  (1) 其中，R1是C1-10烷基，C2-14芳基或类似物，R2是C2-14芳基，C2-9杂环基，C3-10环烷基或类似物，R3是氨基甲酰基，硫氨基甲酰基，异氰酸基，异硫氰酸基，甲酰胺基，硫代甲酰胺基，异腈基，脲基，氨基甲酸酯基或类似物。
• Novel derivatives of bio-affecting phenolic compounds and pharmaceutical composition containing them
  申请人：INTERx RESEARCH CORPORATION

  公开号：EP0046270A1

  公开（公告）日：1982-02-24

  Novel transient prodrug forms of bio-affecting phenolic compounds are selected from the group consisting of those having the structural formula (I): wherein X is O, S or NR5 wherein R5 is hydrogen or lower alkyl; R1 is the mono- or polydehydroxylated residue of a non-steroidal bio-affecting phenol, with the proviso that R' is other than a monohydroxylated or didehydroxylated residue of a phenolic, nuclear dihydroxy natural sympathetic or sympathomimetic amine; R2 is selected from the group consisting of straight or branched chain alkyl, aryl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aralkyl, alkaryl, aralkenyl, aralkynyl, alkenylaryl, alkynylaryl, (lower acyloxy)alkyl, and carboxyalkyl; 3- to 8-membered, saturated or unsaturated mono-heterocyclic or polyheterocyclic containing from 1 to 3 of any one or more of the heteroatoms N, S or O; and mono- or polysubstituted derivatives of the above; R3 is hydrogen, lower acyl, cyano, halo(lower alkyl), carbamyl, lower alkylcarbamyl, di(lower alkyl)carbamyl, CH2ONO2, -CH2OCOR2 or any non-heterocyclic member of the group defined by R2 above; and n is at least one and equals the total number of phenolic hydroxyl functions comprising the non-steroidal bioaffecting phenol etherified via a R2COXCH(R3)0-moiety; those having the structural formula (II): wherein X, R', R2 and R3 are as defined above, and n and m are each at least one and the sum of n+m equals the total number of phenolic hydroxyl functions comprising the non-steroidal bioaffecting phenol either etherified via a R2COXCH(R3)0-moiety or esterified via a R2COO-moiety; and the pharmaceutically acceptable acid addition salts, quaternary ammonium salts and N-oxides thereof.

  生物效应酚类化合物的新型瞬效原药形式选自具有结构式(I)的化合物组成的组： 其中 X 是 O、S 或 NR5，其中 R5 是氢或低级烷基；R1 是非类固醇生物效应酚的单羟基或多羟基残基，但 R' 不是酚、核二羟基天然交感胺或拟交感胺的单羟基或双羟基残基；R2 选自直链或支链烷基、芳基、环烷基、烯基、环烯基、炔基、芳烷基、烷芳基、芳烯基、芳炔基、烯芳基、炔芳基、（低级酰氧基）烷基和羧基烷基组成的组；R3 是氢、低级酰基、氰基、卤代（低级烷基）、氨甲酰基、低级烷基氨甲酰 基、二（低级烷基）氨甲酰基、CH2ONO2、-CH2OCOR2 或上述 R2 定义的基团中的任何非杂环成员；且 n 至少为 1，等于通过 R2COXCH(R3)0 子代醚化的非甾体生物作用酚所包含的酚羟基官能团的总数；具有结构式（II）的酚羟基官能团： 其中 X、R'、R2 和 R3 如上文所定义，n 和 m 至少各为 1，且 n+m 之和等于非甾体类生物效应酚通过 R2COXCH(R3)0 子键醚化或通过 R2COO 子键酯化的酚羟基官能团的总数；及其药学上可接受的酸加成盐、季铵盐和 N-氧化物。
• Method of inhibiting tumor growth using xanthocillin X dimethylether
  申请人：MEIJI SEIKA KAISHA LTD.

  公开号：EP0486944A3

  公开（公告）日：1992-06-03

  Tumor growth in a mammal is inhibited by the administration of an effective amount of xanthocillin X dimethylether. The xanthocillin X dimethylether is administered in a range of 100-3,000 milligrams per day for an average adult human patient. The xanthocillin X dimethylether can be administered orally, by direct application into a neoplastic lesion, or by other parenteral forms of administration including intravenous, subcutaneous, or intramuscular injections. Also, suppository forms can be used.

  服用有效量的黄西林 X 二甲醚可抑制哺乳动物体内的肿瘤生长。对于普通成人患者，黄西林 X 二甲醚的用量范围为每天 100-3000 毫克。黄西林 X 二甲醚可以通过口服、直接应用于肿瘤病灶或其他非肠道给药形式，包括静脉注射、皮下注射或肌肉注射。此外，还可使用栓剂形式。
• THROMBOPOETIN RECEPTOR ACTIVATOR AND PROCESS FOR PRODUCING THE SAME
  申请人：Nissan Chemical Industries, Ltd.

  公开号：EP1552828A1

  公开（公告）日：2005-07-13

  A preventive, therapeutic or improving agent for diseases against which activation of the thrombopoietin receptor is effective or a platelet increasing agent, which contains a thrombopoietin receptor activator represented by the formula (1): [wherein each of R1 and R3 is independently a hydrogen atom, SO3H, a C1-6 alkyl group, a C1-6 alkylcarbonyl group or a C6-18 arylcarbonyl group (the C1-6 alkyl group, the C1-6 alkylcarbonyl group and the C6-18 arylcarbonyl group may be optionally substituted with a halogen atom, a hydroxyl group, a C2-6 alkenyl group, a C1-6 alkoxy group, a C1-6 alkoxycarbonyl group, a C6-18 aryl group, a 2-pyridyl group, a 3-pyridyl group, a 4-pyridyl group, a 2-furanyl group, a 3-furanyl group, a 2-thienyl group, a 3-thienyl group or NR9R10), and each of R2, R4 and Ra is independently a hydrogen atom, a hydroxyl group or a C1-6 alkoxy group].

  一种对激活血小板生成素受体有效的疾病的预防、治疗或改善药物，或一种血小板增加剂，其中含有由式(1)代表的血小板生成素受体激活剂： C1-6烷氧基、C1-6烷氧羰基、C6-18芳基、2-吡啶基、3-吡啶基、4-吡啶基、2-呋喃基、3-呋喃基、2-噻吩基、3-噻吩基或 NR9R10），且 R2、R4 和 Ra 各自独立地为氢原子、羟基或 C1-6 烷氧基]。