四乙基锡 | 597-64-8

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机过渡后金属化合物
• 中文名称: 四乙基锡
• 中文别名: 四乙锡；四乙錫
• 英文名称: tetraethyltin
• CAS: 597-64-8
• 化学式: C₈H₂₀Sn
• 分子量: 234.957
• InChiKey: RWWNQEOPUOCKGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  9
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

ADMET

代谢

四乙基锡脱烷基到三乙基锡的速度是快的。

The dealkylation of tetraethyltin to triethyltin ... is fast. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

四乙基锡转化为三乙基锡确保了在用四乙基锡或三乙基锡处理后，锡的相对分布和化学形态相似。

The metabolism of tetraethyltin to triethyltin assures that the relative distribution and chemical forms of tin are similar after treatment with tetraethyl- or triethyltin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

Tetraethyltin在离体大鼠肝脏微粒体中迅速代谢，并且在大鼠静脉注射后形成三乙基锡衍生物。此外，还表明三乙基锡产物在体外系统中进一步代谢为二乙基锡衍生物。

Tetraethyltin was rapidly metabolized by isolated rat liver microsome preparations, and in rats after iv injection, to form triethyltin derivatives. Also, the triethyltin products were shown to be metabolized further to diethyltin derivatives in an in vitro system.

来源:Hazardous Substances Data Bank (HSDB)

代谢

还原型烟酸腺嘌呤二核苷酸磷酸和氧气依赖的微粒体代谢二、三、四乙基取代的锗、锡和铅衍生物在大鼠中产生了乙烯作为主要产物和乙烷作为次要产物。这些反应由肝脏微粒体细胞色素P450依赖的单加氧酶催化。由于无氧条件对乙烷和乙烯的形成有不同的抑制作用，结果提示大部分产生的乙烷是通过还原机制衍生而来的。三乙基锡溴化物在还原型烟酸腺嘌呤二核苷酸磷酸的存在下将细胞色素P450转化为细胞色素P420，并在体外影响单加氧酶的功能。四乙基锡导致还原型烟酸腺嘌呤二核苷酸磷酸和随时间形成的细胞色素P420，这表明四乙基锡转化为了在显著浓度下的三乙基锡盐。形成细胞色素P420的效力顺序与锡衍生物在体外诱导微粒体脂质过氧化的能力密切相关。

The reduced form of nicotinamide-adenine dinucleotide phosphate and oxygen dependent microsomal metabolism of the di-, tri- and tetra-ethyl-substituted derivatives of germanium, tin, and lead gave rise to ethylene as a major product and ethane as a minor product in rats. These reactions were catalyzed by liver microsomal cytochrome p450-dependent monooxygenase. Since formation of ethane and ethylene was differentially inhibited by anaerobiosis, results suggested that a large portion of the ethane produced was derived by a reductive mechanism. Triethyltin bromide in the absence and presence of the reduced form of nicotinamide-adenine dinucleotide phosphate converted cytochrome p450 into cytochrome p420 and affected the function of monooxygenase in vitro. Tetraethyltin caused the reduced form of nicotinamide-adenine dinucleotide phosphate and the time-dependent formation of cytochrome p420, suggesting that tetraethyltin was converted into triethyltin salts in significant concentrations. The order of potency in formation of cytochrome p420 was closely paralleled by the ability of tin derivatives to induce microsomal lipid peroxidation in vitro.

来源:Hazardous Substances Data Bank (HSDB)

代谢

一些乙基取代的有机锡化合物在大鼠离体肝细胞中的代谢和毒性被研究了。四乙基锡和三乙基锡衍生物被离体大鼠肝细胞代谢，产生乙烷和乙烯。四乙基锡产生的烃类物质比三乙基锡溴化物多，乙烯是四乙基锡代谢的主要产物（95%）。在浓度为100微摩的三乙基锡盐中，未经处理的大鼠细胞形成的主要产物是乙烷。体内用苯巴比妥预处理后，烃类总产率显著增加，乙烯比例发生变化；乙烯成为主要代谢产物。体内用5,6-苯并黄酮预处理后，烃类总产率略有下降。未检测到二乙基锡二氯化物（100微摩）在离体大鼠肝细胞中的代谢物。三乙基锡溴化物（100微摩）对来自苯巴比妥预处理大鼠的离体肝细胞中的双苯酚的Ⅰ相（氧化）和Ⅱ相（结合）代谢有强烈抑制作用：二乙基锡二氯化物特别影响芳烃的Ⅰ相代谢。三乙基和二乙基锡盐减少了这些细胞的氧气消耗和ATP水平，其中三乙基衍生物的效果更明显。四乙基锡对肝细胞没有明显的毒性。从苯巴比妥预处理的大鼠中分离的细胞通过台盼蓝染色排除和乳酸脱氢酶的丢失表明，三乙基锡溴化物的毒性大于二乙基锡二氯化物。与三乙基锡相比，二乙基衍生物在促进脂质过氧化方面更为有效，表现为硫代巴比妥酸反应产物的形成。

The metabolism and toxicity of some ethyl-substituted organotin compounds in isolated rat hepatocytes were studied. Tetra- and triethyltin derivatives were metabolized by isolated rat hepatocytes to yield ethane and ethylene. Hydrocarbon formation from tetraethyltin was larger than that obtained with triethyltin bromide and ethylene was the major product (95%) of tetraethyltin metabolism. At a triethyltin salt concentration of 100 uM, the major product formed by cells from untreated rats was ethane. Pretreatment in vivo by phenobarbital resulted in a marked increase in the overall rate of hydrocarbon production and a change in ethylene ratio; ethylene was the predominant metabolite produced. 5,6-Benzoflavone pretreatment in vivo resulted in a small depression in overall hydrocarbon production. No metabolites of diethyltin dichloride (100 uM) by isolated rat heptocytes was detected. Triethyltin bromide (100 uM) was a potent inhibitor of phase 1 (oxidation) and phase 2 (conjugation) metabolism of biphenyl in isolated hepatocytes from phenobarbital-pretreated rats: diethyltin dichloride affected particularly the phase 1 metabolism of the aromatic hydrocarbon. Triethyl- and diethyltin salts reduced O2 consumption and ATP levels in these cells. The triethyl derivative was more effective. Tetraethyltin was not apparently toxic to hepatocytes. Trypan blue dye exclusion and lactate dehydrogenase loss by the cell isolated from phenobarbital-pretreated rats indicated that triethyltin bromide was more toxic than diethyltin dichloride. The diethyl derivative was more potent in stimulating lipid peroxidation as indicated by the formation of thiobarbituric acid-reactive products than triethyltin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

有机锡化合物产生神经毒性和免疫毒性效应。有机锡可能直接激活胶质细胞，通过局部释放促炎症细胞因子、肿瘤坏死因子-α和/或白细胞介素，从而促进神经细胞退化。它们还可能通过直接作用于神经细胞来诱导凋亡。有机锡化合物刺激脑组织中神经递质的释放和/或减少神经细胞对神经递质的摄取，包括天冬氨酸、GABA、谷氨酸、去甲肾上腺素和血清素。这可能是神经细胞损失的一个促成因素或结果。有机锡的免疫毒性特征是由抑制未成熟胸腺细胞的增殖和成熟胸腺细胞的凋亡引起的胸腺萎缩。人们认为有机锡化合物通过抑制DNA和蛋白质合成、诱导参与凋亡的基因（如nur77）的表达以及破坏细胞内钙水平的调节来发挥这些效应，从而导致不受控制的活性氧种类的产生、细胞色素c释放到细胞质中以及凋亡的蛋白水解和核酸水解级联。未成熟胸腺细胞增殖的抑制进一步导致T细胞介导的免疫反应的抑制。有机锡也是内分泌干扰物，被认为通过不适当的受体激活导致脂肪细胞分化，从而促进肥胖。无机锡触发红细胞溶解，导致锡诱导的贫血。(L308, A182, A184)

Organotin compounds produce neurotoxic and immunotoxic effects. Organotins may directly activate glial cells contributing to neuronal cell degeneration by local release of pro-inflammatory cytokines, tumor necrosis factor-_, and/or interleukins. They may also induce apoptosis by direct action on neuronal cells. Organotin compounds stimulate the neuronal release of and/or decrease of neuronal cell uptake of neurotransmitters in brain tissue, including aspartate, GABA, glutamate, norepinephrine, and serotonin. This may be either a contributing factor to or result of the neuronal cell loss. The immunotoxic effects of organotins are characterized by thymic atrophy caused by the suppression of proliferation of immature thymocytes and apoptosis of mature thymocytes. Organotin compounds are believed to exert these effects by suppressing DNA and protein synthesis, inducing the expression of genes involved in apoptosis (such as nur77), and disrupting the regulation of intracellular calcium levels, giving rise to the uncontrolled production of reactive oxygen species, release of cytochrome c to the cytosol, and the proteolytic and nucleolytic cascade of apoptosis. The suppression of proliferation of immature thymocytes further results in the suppression of T-cell-mediated immune responses. Organotins are also endocrine disruptors and are believed to contribute to obesity by inappropriate receptor activation, leading to adipocyte differentiation. Inorganic tin triggers eryptosis, contributing to tin-induced anemia. (L308, A182, A184)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌性证据

A4；不能分类为人类致癌物。/锡，有机化合物，作为Sn/

A4; Not classifiable as a human carcinogen. /Tin, organic cmpd, as Sn/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

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

吸入或吞咽有机锡，或者皮肤接触有机锡，可能会干扰大脑和神经系统的工作方式，严重情况下可能导致死亡。有机锡化合物还可能损害免疫和生殖系统。

Breathing or swallowing, or skin contact with organotins, can interfere with the way the brain and nervous system work, causing death in severe cases. Organic tin compounds may also damage the immune and reproductive system. (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)

安全信息

• 储存条件：
  | 冰箱 (+4°C) | 毒气室 |

反应信息

• 作为反应物：
  描述：

  四乙基锡 在 Br₂ 作用下， 以 四氯化碳 为溶剂， 生成 三乙基溴化锡
  参考文献：
  名称：

  Gmelin Handbuch der Anorganischen Chemie, Gmelin Handbook: Sn: Org.Verb.2, 1.1.2.2.1, page 157 - 162

  摘要：

  DOI：
• 作为产物：
  描述：

  stannane 在 乙烯 作用下， 以34%的产率得到四乙基锡
  参考文献：
  名称：

  Stannane

  摘要：

  DOI：

  10.1021/ja01037a054
• 作为试剂：
  描述：

  4-氟-3-甲基苯胺 在 四乙基锡 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.16h， 生成 2-ethyl-N-(4-fluoro-3-methylphenyl)-5-[[(3S)tetrahydrofuran-3-yl]sulfamoyl]thiophene-3-carboxamide
  参考文献：
  名称：

  [EN] SULPHAMOYLTHIOPHENAMIDE DERIVATIVES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B
  [FR] DÉRIVÉS DE SULPHAMOYLTHIOPHÉNAMIDES ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS POUR LE TRAITEMENT DE L'HÉPATITE B

  摘要：

  HBV复制抑制剂，包括式(I)的立体异构体、盐、水合物、溶剂化物，其中X和R1至R8的含义如本文所述。本发明还涉及制备这些化合物的方法、含有它们的药物组合物及其用途，单独使用或与其他HBV抑制剂联合使用，用于HBV治疗。

  公开号：

  WO2014184365A1

文献信息

• The effect of halide ions in the alkylation of lead and tin
  作者：Riccardo Galli、Bindo M. Giannaccari、Luigi Cassar

  DOI：10.1016/s0022-328x(00)87843-2

  日期：1970.12

  The effect of various nucleophilic species, both neutral and charged, on the alkylation reaction of Pb and Sn by Grignard compounds has been studied. The following activation series has been observed: carbitols ⋍ I− > tetrahydrofuran, tetrahydrothiophene > Et2O⋍Et3N⋍Br−

  研究了中性和带电的各种亲核物质对格氏试剂对Pb和Sn烷基化反应的影响。以下激活系列已经观察到：卡必醇⋍我- >四氢呋喃，四氢噻>的Et 2 O⋍Et 3 N⋍Br -
• QUINAZOLINE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Hadd Michael J.

  公开号：US20120053174A1

  公开（公告）日：2012-03-01

  Provided herein are quinazoline compounds for treatment of JAK kinase mediated diseases, including JAK2 kinase-, JAK3 kinase- or TYK2 kinase-mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.

  本文提供了喹唑啉化合物，用于治疗JAK激酶介导的疾病，包括JAK2激酶、JAK3激酶或TYK2激酶介导的疾病。还提供了包含这些化合物的药物组合物以及使用这些化合物和组合物的方法。
• PYRROLO- AND THIAZOLO-PYRIDINE COMPOUNDS, AND METHODS OF USE THEREOF
  申请人：DENG Shaojiang

  公开号：US20080004309A1

  公开（公告）日：2008-01-03

  The present invention relates to novel compounds capable of modulating the stability and/or activity of hypoxia inducible factor (HIF).

  这项发明涉及一种能够调节缺氧诱导因子（HIF）稳定性和/或活性的新化合物。
• Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments
  申请人：Auckland Uniservices Limited

  公开号：EP1468688A2

  公开（公告）日：2004-10-20

  The present invention relates to a synergetistic composition comprising one or more benzoazine-mono-N-oxides, and one or more benzoazine 1,4 dioxides for use in cancer therapy. The invention also provides a range of novel 1,2,4 benzoazine-mono-N-oxides and related analogues. These can be used as potentiators of the cytotoxicity of existing anticancer drugs and therapies for cancer treatment.

  本发明涉及一种协同组合物，包括一种或多种苯并噁唑-单-N-氧化物，以及一种或多种苯并噁唑1,4-二氧化物，用于癌症治疗。 该发明还提供了一系列新颖的1,2,4苯并噁唑-单-N-氧化物及相关类似物。这些可以用作增强现有抗癌药物的细胞毒性和癌症治疗的治疗剂。
• SUBSTITUTED 2- AMIDOQUINAZOL-4-ONES AS MATRIX METALLOPROTEINASE-13 INHIBITORS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20150329556A1

  公开（公告）日：2015-11-19

  The present invention provides a novel amide derivative having a matrix metalloproteinase inhibitory activity, and useful as a pharmaceutical agent, which is a compound represented by the formula (I) wherein ring A is an optionally substituted, nitrogen containing heterocycle, ring B is an optionally substituted monocyclic homocycle or an optionally substituted monocyclic heterocycle, Z is N or NR 1 (R 1 is a hydrogen atom or an optionally substituted hydrocarbon group), is a single bond or a double bond, R 2 is a hydrogen atom or an optionally substituted hydrocarbon group, X is an optionally substituted spacer having 1 to 6 atoms, ring C is (1) an optionally substituted homocycle or (2) an optionally substituted heterocycle other than a ring represented by (II) (X′ is S, O, SO, or CH 2 ), and at least one of ring B and ring C has substituent(s), provided that N-(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]2 hydroxypropyl}5,6 dimethyl 4 oxo 1,4 dihydrothieno[2,3-d]pyrimidine-2-carboxamide is excluded, or a salt thereof.

  本发明提供了一种新型酰胺衍生物，具有基质金属蛋白酶抑制活性，并且作为药用剂是有用的，该化合物由以下式(I)表示，其中环A是一个可选择取代的含氮杂环，环B是一个可选择取代的单环同核环或可选择取代的单环杂环，Z是N或NR1（R1是氢原子或可选择取代的碳氢基团），是一个单键或双键，R2是氢原子或可选择取代的碳氢基团，X是一个具有1到6个原子的可选择取代的间隔物，环C是（1）一个可选择取代的同核环或（2）一个除了由（II）表示的环之外的可选择取代的杂环（X′是S、O、SO或CH2），并且环B和环C中至少有一个有取代基，但不包括N-(1S,2R)-1-(3,5-二氟苄基)-3-[(3-乙基苄基)氨基]2-羟基丙基}5,6-二甲基-4-氧代-1,4-二氢噻唑并[2,3-d]嘧啶-2-羧酰胺，或其盐。

表征谱图