aurothioglucose | 577779-48-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: aurothioglucose
• 英文别名: ATG；Aureotan；gold(1+);(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxane-2-thiolate
• CAS: 577779-48-7
• 化学式: Au*C₆H₁₁O₅S
• 分子量: 392.183
• InChiKey: XHVAWZZCDCWGBK-WYRLRVFGSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.67
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  91.2
• 氢给体数：
  4
• 氢受体数：
  6

ADMET

代谢

尽管对金硫甘醇的具体代谢命运没有正式的了解，但是在给予患者药物后，可以在尿液和血液中找到的主要金物种是[Au(CN)2]-。

Although the exact metabolic fate of aurothioglucose is not formally understood, the principal gold species that can be found in the urine and blood of a patient following the administration of the drug is [Au(CN)2]-.

来源:DrugBank

代谢

接受金钠硫代硫酸盐治疗的病人尿中的主要金物种是[Au(CN)2]-，这也出现在血液的低分子量浸润中。同样的化合物也出现在服用硫酸醇的病人的尿液和血液中。

For a patient receiving gold sodium thiomalate the principal gold species in the urine is [Au(CN)2]-, which is also seen in a low molecular weight infiltrate of the blood. The same compound is also identified in the urine and blood of a patient taking solganol

来源:Hazardous Substances Data Bank (HSDB)

代谢

接受金钠硫代硫酸盐治疗的病人尿中的主要金物种是[Au(CN)2]-，这也出现在血液的低分子量浸润中。同样的化合物也出现在服用硫酸醇的病人的尿液和血液中。

For a patient receiving gold sodium thiomalate the principal gold species in the urine is [Au(CN)2]-, which is also seen in a low molecular weight infiltrate of the blood. The same compound is also identified in the urine and blood of a patient taking solganol

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：金硫葡萄糖

IARC Carcinogenic Agent:Aurothioglucose

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第13卷：（1977年）一些杂项药物物质

IARC Monographs:Volume 13: (1977) Some Miscellaneous Pharmaceutical Substances

来源:International Agency for Research on Cancer (IARC)

毒理性

• 解毒与急救

如果出现毒性反应，应立即停止金疗法。在出现轻微反应的情况下，可能只需短暂停止注射Solganal（金硫葡萄糖）悬浮液，然后以较小剂量恢复治疗。

In the event of toxic reactions gold therapy should be discontinued immediately. In the presents of mild reactions, it may be sufficient to discontinue the administration of Solganal /aurothioglucose/ suspension for a short period and then to resume treatment with smaller doses.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

皮炎和瘙痒可能对舒缓乳膏、其他适当的抗瘙痒治疗或局部糖皮质激素有反应。

Dermatitis and pruritus may respond to soothing lotions, other appropriate antipruritic treatment or topical glucocorticoids.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

通常情况下，金硫葡萄糖是通过肌肉注射给药的，最好是在臀部肌肉注射，之后吸收通常是缓慢且不规则的。金从注射部位被吸收，大约在4到6小时后在血液中达到峰值浓度。在两个受试者中单次肌肉注射50毫克金硫葡萄糖悬浮液后，观察到血清峰值水平大约为235 g/dL和450 g/dL。金在人体组织中的储存取决于器官的质量以及金的浓度。因此，含金量最高的组织（按重量比）不一定含有最多的金。金浓度最高的通常是在淋巴结、肾上腺、肝脏、肾脏、骨髓和脾脏中。实际上，在关节结构中发现的金浓度相对较低。特别是，在给予金硫葡萄糖剂量后，大约85%的血浆金将被储存在主要的身体金库中，按总金含量递减的顺序是淋巴结、骨髓、肝脏、皮肤和骨骼。

In general, aurothioglucose is administered via intramuscular injection - preferably intragluteally - after which the resultant absorption is typically slow and erratic. Gold is absorbed from injection sites, reaching peak concentration in blood in about 4 to 6 hours. After a single intramuscular injection of 50 mg of aurothioglucose suspension in two subjects, peak serum levels were observed at approximately 235 g/dL and 450 g/dL. Storage of gold in human tissues depends upon organ mass as well as the concentration of gold.Subsequently, tissues having the highest gold levels (w/w) may not necessarily have the largest total amounts of gold. The highest concentrations of gold are generally found in the lymph nodes, adrenal glands, liver, kidneys, bone marrow, and spleen. Relatively small concentrations are actually found in the articular structures. In particular, following the administration of aurothioglucose doses, about 85% of the resultant plasma gold will be stored in the major bodily gold depots, which in decreasing order of total gold content are, the lymph nodes, bone marrow, liver, skin, and bone.

来源:DrugBank

吸收、分配和排泄

• 消除途径

在两名患者肌肉注射50毫克金硫葡萄糖后，一项研究发现大约70%的药物通过尿液排出，30%通过粪便排出。总的来说，金硫葡萄糖主要通过尿液排出。

Following a single intramuscular injection of 50 mg aurothioglucose in each of two patients, one study determined that approximately 70% of the agent is eliminated in the urine and 30% in the faeces. In general, excretion is primarily in the urine.

来源:DrugBank

吸收、分配和排泄

• 分布容积

关于金硫葡萄糖分布体积的容易获取的数据并不存在。

Readily accessible data regarding the volume of distribution of aurothioglucose is not available.

来源:DrugBank

吸收、分配和排泄

• 清除

当遵循每周一次的标准金硫葡萄糖治疗计划时，大约40%的给药剂量每周被排出，而剩余的剂量会在更长的时间内被排出。

When a standard weekly treatment schedule of aurothioglucose administrations is followed, about 40% of the given dose is excreted each week, while the remainder is excreted over a longer period.

来源:DrugBank

吸收、分配和排泄

金化合物（包括金硫葡萄糖）的真实潜力尚未被明确界定，但可以肯定的是，与使用口服金化合物相比，在治疗期间，身体会保留大量金。

The true potential of gold compounds, including ... aurothioglucose, to cumumulate has not been clearly defined, but it is clear that substantially larger amounts of gold are retained in the body during therapy with parenteral gold compounds than during therapy with auranofin.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  aurothioglucose 、 2-Dimethylaminomethyl-benzeneselenol 生成
  参考文献：
  名称：

  抗关节炎金化合物抑制谷胱甘肽过氧化物酶的合成模型

  摘要：

  在本文中，对两种合成的有机硒化合物双[2-（N，N-二甲基氨基）苄基]二硒化物（5）和双[2-（N，N-二甲基氨基）苄基]硒化物（9）的谷胱甘肽过氧化物酶活性的抑制）中，由金（I）硫葡萄糖（1），氯（三乙基膦）金（I），氯（三甲基膦）金（I）和氯（三苯基膦）金（I）进行说明。发现抑制作用相对于过氧化物（H 2 O 2）底物是竞争性的，而相对于硫醇（PhSH）共底物是不竞争的。二硒化物5与PhSH反应生成相应的硒醇（6），将其用1个当量的金处理（I）氯化物产生相应金selenolate络合物11 - 13。然而，加入1个当量的硒醇的6至络合物11 - 13个导致形成双selenolate络合物14通过涉及膦配位体的配位体消除置换反应。从这些反应消除了膦配位体被进一步转化为相应的氧化膦（R 3 P = O）和硒化物（R 3 P═Se）。除了用硒醇6取代膦配体，还观察到两个不同的膦配体之间的互换

  DOI：

  10.1021/ic8019183

文献信息

• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
  申请人：BIOCAD JOINT STOCK CO

  公开号：WO2018092047A1

  公开（公告）日：2018-05-24

  The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.

  本发明涉及一种新的化合物，其化学式为I：或其药学上可接受的盐、溶剂化合物或立体异构体，其中：V1为C或N，V2为C(R2)或N，如果V1为C，则V2为N，如果V1为C，则V2为C(R2)，或者如果V1为N，则V2为C(R2)；每个n，k独立地为0或1；每个R2，R11独立地为H，D，Hal，CN，NR'R"，C(O)NR'R"，C1-C6烷氧基；R3为H，D，羟基，C(O)C1-C6烷基，C(O)C2-C6烯基，C(O)C2-C6炔基，C1-C6烷基；R4为H，Hal，CN，CONR'R"，羟基，C1-C6烷基，C1-C6烷氧基；L为CH2，NH，O或化学键；R1从包括的片段组中选择：片段1，片段2，片段3，每个A1，A2，A3，A4独立地为CH，N，CHal；每个A5，A6，A7，A8，A9独立地为C，CH或N；R5为H，CN，Hal，CONR'R"，C1-C6烷基，未取代或被一个或多个卤素取代；每个R'和R"独立地从包括H，C1-C6烷基，C1-C6环烷基，芳基的组中选择；R6从组中选择：[化学式II]每个R7，R8，R9，R10独立地为乙烯基，甲基乙炔基；Hal为CI，Br，I，F，具有布鲁顿酪氨酸激酶（Btk）抑制剂的性质，以及含有这种化合物的药物组合物，以及它们作为治疗疾病和紊乱的药物的用途。
• [EN] BRUTON'S TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：PFIZER

  公开号：WO2014068527A1

  公开（公告）日：2014-05-08

  Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. (Formula I)

  本文披露了一种与Bruton's酪氨酸激酶（BTK）形成共价键的化合物。公开了制备这些化合物的方法。还披露了包括这些化合物的药物组合物。公开了使用BTK抑制剂的方法，单独或与其他治疗剂联合治疗自身免疫疾病或症状、异源免疫疾病或症状、癌症，包括淋巴瘤，以及炎症性疾病或症状的方法。 (化学式I)
• IRAK DEGRADERS AND USES THEREOF
  申请人：Kymera Therapeutics, Inc.

  公开号：US20190192668A1

  公开（公告）日：2019-06-27

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用这些化合物的方法。
• Amino-substituted heterocycles, compositions thereof, and methods of treatment therewith
  申请人：D'Sidocky Neil R.

  公开号：US20080242694A1

  公开（公告）日：2008-10-02

  Provided herein are Heterocyclic Compounds having the following structure: wherein R 1 , R 2 , X, Y and Z are as defined herein, compositions comprising an effective amount of a Heterocyclic Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heterocyclic Compound to a patient in need thereof.

  本文提供具有以下结构的杂环化合物： 其中R1、R2、X、Y和Z如本文所定义，包含有效量杂环化合物的组合物，以及治疗或预防癌症、炎症性疾病、免疫疾病、代谢性疾病以及通过给予患者需要的有效量杂环化合物来抑制激酶途径治疗或预防的疾病的方法。
• COMPOUNDS THAT MODULATE INTRACELLULAR CALCIUM
  申请人：Whitten Jeffrey P.

  公开号：US20110263612A1

  公开（公告）日：2011-10-27

  Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity.

  本文描述了含有这些化合物的化合物和药物组合物，这些化合物调节储存操作钙（SOC）通道的活性。本文还描述了使用这种SOC通道调节剂的方法，单独或与其他化合物结合，用于治疗需要抑制SOC通道活性的疾病或症状。