二十二烷-1-醇 | 661-19-8

• 物质功能分类: 化学试剂 - 有机试剂 - 脂肪醇
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 二十二烷-1-醇
• 中文别名: 1-二十二醇；1-二十二烷醇；山嵛醇及其乳膏；山萮醇；山嵛醇；C22醇；正二十二醇；二十二烷醇；多可沙诺；正二十二烷醇
• 英文名称: 1-docosanol
• 英文别名: docosan-1-ol；behenyl alcohol；docosanol；behenic alcohol
• CAS: 661-19-8；30303-65-2
• 化学式: C₂₂H₄₆O
• mdl: MFCD00002939
• 分子量: 326.607
• InChiKey: NOPFSRXAKWQILS-UHFFFAOYSA-N

物化性质

• 熔点：
  65-72 °C(lit.)
• 沸点：
  180 °C0.22 mm Hg(lit.)
• 密度：
  d75 0.8063 g/ml; d85 0.7986 g/ml; d95 0.7911 g/ml
• 溶解度：
  氯仿（微溶）、乙酸乙酯（微溶）
• LogP：
  8.3 at 20℃
• 物理描述：
  Liquid; OtherSolid; OtherSolid, Liquid; PelletsLargeCrystals; PelletsLargeCrystals, OtherSolid
• 颜色/状态：
  Colorless waxy solid
• 蒸汽压力：
  6.1X10-8 mm Hg (est)
• 表面张力：
  21.82 dyne/cm at 75 °C; 21.27 dyne/cm at 85 °C; 20.53 dyne/cm at 95 °C
• 折光率：
  Index of refraction = 1.4360 at 75 °C/D
• 保留指数：
  2470.4;2475;2476;2468;2473;2443

计算性质

• 辛醇/水分配系数(LogP)：
  10.5
• 重原子数：
  23
• 可旋转键数：
  20
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

二十二碳醇，即正二十二烷醇，在体外展现出对多种脂质包膜病毒的 抗病毒活性，包括单纯疱疹病毒1型和2型，其作用机制是干扰病毒正常进入靶细胞。我们之前报告指出，哺乳动物细胞会摄入大量的放射性标记的正二十二烷醇。在这里，我们报告细胞会广泛代谢摄入的醇。这一现象的证据是，多达60%的与细胞相关的放射性标记被整合到与磷脂酰胆碱和磷脂酰乙醇胺共同纯化的磷脂中。通过化学（Vitride）还原分析表明，正二十二烷醇的很大一部分被氧化成正二十二烷酸，然后作为极性脂质上的酰基团被整合。然而，一定量的放射性标记对Vitride还原具有抗性，这与正二十二烷醇被整合到醚脂质中相一致。正二十二烷醇的代谢转化速率和程度随细胞类型和用于悬浮化合物的表面活性剂而变化。此外，正二十二烷醇的抗HSV活性与其观察到的代谢量成正比。这些发现表明，正二十二烷醇的抗HSV活性涉及细胞的摄取和药物代谢。

The 22-carbon fatty alcohol, n-docosanol, exhibits in vitro antiviral activity against several lipid-enveloped viruses including herpes simplex viruses 1 and 2 by a mechanism that interferes with normal viral entry into target cells. We previously reported that mammalian cells incorporate significant quantities of radiolabeled n-docosanol. Herein, we report that cells extensively metabolize the internalized fatty alcohol. This is evidenced by incorporation of up to 60% of cell-associated radiolabel into phospholipids that copurify with phosphatidylcholine and phosphatidylethanolamine. Analysis by chemical (Vitride) reduction suggests that a significant portion of n-docosanol is oxidized to n-docosanoic acid and then incorporated as an acyl group on polar lipids. A measurable amount of radiolabel, however, is resistant to Vitride reduction, consistent with incorporation of n-docosanol into ether lipids. The rate and extent of metabolic conversion of n-docosanol vary with the cell type and surfactant used to suspend the compound. Furthermore, the anti-HSV activity of n-docosanol is quantitatively proportional to the amount of metabolism observed. These findings suggest that the anti-HSV activity of n-docosanol involves cellular uptake and metabolism of the drug.

来源:Hazardous Substances Data Bank (HSDB)

代谢

一组由顺式-9[1(-14)C]十八烯醇和[1(-14)C]二十二烷醇混合的化合物被注射到19天大的大鼠大脑中。这两种醇被大脑代谢，但速率不同；每一种都被氧化为相应的脂肪酸。大量的放射性物质被整合到乙醇胺磷脂的18:1烷基和烯基链以及胆碱磷脂的18:1烷基链中。

A mixture of cis-9[1(-14)C] octadecenol and [1(-14)C] docosanol was injected into the brains of 19-day-old rats. Both alcohols were metabolized by the brain but at different rates; each was oxidized to the corresponding fatty acid. Substantial amounts of radioactivity were incorporated into 18:1 alkyl and alk-1-enyl moieties of the ethanolamine phosphoglycerides and into 18:1 alkyl moieties of the choline phosphoglycerides.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

洋地黄苷对心脏的作用被长链脂肪酸和醇类抑制；[J. Mol Cell Cardiol 12(9) 847 (1980)] 长链脂肪酸和醇类抑制了标记有(3)H的洋地黄苷与来自狗心脏的颗粒组分特异性结合。抑制程度随着链长的增加而增加，在饱和脂肪酸、不饱和脂肪酸和醇类中分别以月桂酸、肉豆蔻油酸和癸醇达到最大值，随后随着同系物系列中链长更长的成员而下降。[KIM RS, LABELLA FS；特异性结合]

-Ouabain to heart is inhibited by long-chain fatty acids and alcohols; [J. Mol Cell Cardiol 12(9) 847 (1980)] Long-chain fatty acids and alcohols inhibit specific binding of (3)H-labeled ouabain to a particulate fraction from dog heart. The magnitude of inhibition increased with chain length, reaching max with lauric acid, myristoleic acid, and decanol in a series of saturated fatty acids, unsaturated fatty acids, and alcohols, respectively, followed by a decline with longer chain members of homologous series.[KIM RS, LABELLA FS; SPECIFIC BINDING OF

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

阿昔洛韦（ACV）对单纯疱疹病毒（HSV）的活性通过与多可沙诺治疗细胞，可以协同增强，表现为抑制子代病毒产生和斑块形成。这种阿昔洛韦和多可沙诺之间的药物相互作用在HSV-1和HSV-2的实验室株、口腔和生殖器临床分离株、巨细胞病毒（CMV）和水痘带状疱疹病毒（VZV）中均观察到。多可沙诺和阿昔洛韦的近最佳浓度组合能比单独使用任何一种药物抑制HSV复制的效果提高超过99%，包括对阿昔洛韦耐药变异株的出现。这种反应在非洲绿猴肾细胞、正常人类包皮细胞和正常人类肺细胞中均可观察到。多可沙诺治疗细胞还能协同增强三氟胸苷（TFT）、腺嘌呤阿拉伯糖苷（Ara-A）和利巴韦林对HSV产生的抑制作用。多可沙诺和磷酰甲酸（PFA）联用显示出对HSV的加成抗病毒效果。当多可沙诺与阿昔洛韦、TFT、Ara-A、利巴韦林、PFA、8-氮鸟嘌呤或5-氟尿嘧啶联合使用时，没有发现协同抑制细胞DNA合成或诱导明显细胞毒性的证据。

... The anti-HSV activity of acyclovir (ACV) was synergistically enhanced by treatment of cells with docosanol as judged by inhibition of progeny virus production and plaque formation. This drug interaction between ACV and docosanol was observed with laboratory strains of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), oral and genital clinical isolates of HSV, cytomegalovirus (CMV), and varicella zoster virus (VZV). Near optimal concentrations of docosanol plus ACV inhibited HSV replication >99% more than either drug alone, including emergence of ACV-resistant variants. The response was observed with African Green Monkey kidney cells, normal human foreskin cells, and normal human lung cells. Treatment of cells with docosanol also synergistically intensified the inhibition of HSV production by trifluorothymidine (TFT), adenine arabinoside (Ara-A), and ribavirin. An additive anti-HSV effect was observed with docosanol and phosphonoformate (PFA). No evidence was found for either synergistic inhibition of cellular DNA synthesis or induction of overt cellular toxicity when docosanol was combined with ACV, TFT, Ara-A, ribavirin, PFA, 8-azaguanine, or 5-fluorouracil.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

对肠道粘膜脂质成分的脂肪酸对几种药物通过由卵磷脂和肠道脂质生成的双层脂质膜透过性的影响进行了研究。当月桂酸、硬脂酸、油酸、亚油酸和亚麻酸等脂肪酸被引入由磷脂酰胆碱生成的双层脂质膜时，对氨基苯甲酸、水杨酸和对氨水杨酸（带负电荷的药物）的透过性系数增加了。在存在甲基亚油酸和油醇的情况下，对氨基苯甲酸的转移没有获得增强效果。脂肪酸的作用在pH 6.5时比在pH 4.5时更为明显。相反，当向原本含有脂肪酸的肠道脂质膜中加入脂肪酸时，对氨基苯甲酸的透过性系数倾向于降低，尽管通过肠道脂质膜的透过性大于磷脂酰胆碱膜。当向肠道磷脂中加入脂肪酸时，对氨基苯甲酸通过肠道磷脂双层脂质膜的透过性显著降低，几乎等于磷脂酰胆碱膜的透过性，并恢复到肠道脂质膜的值。似乎有理由假设，肠道中性脂质分中的游离脂肪酸可以增加对氨基苯甲酸的透过性。基于上述结果，讨论了弱酸性药物从肠道良好吸收的可能机制。

Studies of the influence of fatty acids, which were the component of intestinal mucosal lipids, on the permeability of several drugs across bilayer lipid membranes generated from egg phosphatidylcholine and intestinal lipid have been pursued. The permeability coefficients of p-aminobenzoic acid, salicylic acid and p-aminosalicylic acid (anionic-charged drug) increased when fatty acids such as lauric, stearic, oleic, linoleic and linolenic acid were incorporated into the bilayer lipid membranes generated from phosphatidylcholine. In the presence of methyl linoleate and oleyl alcohol, no enhancing effect on p-aminobenzoic acid transfer was obtained. The effect of fatty acids was more marked at pH 6.5 than at pH 4.5. In contrast, upon the addition of fatty acids to intestinal lipid membranes which originally contained fatty acids, the permeability coefficient of p-aminobenzoic acid tended to decrease, though the permeability through intestinal lipid membranes was larger than that of phosphatidylcholine membranes. The permeability of p-aminobenzoic acid across bilayer lipid membranes from intestinal phospholipids was significantly decreased to about equal that of phosphatidylcholine membranes, and reverted to the value of intestinal lipid membranes when fatty acids were added to intestinal phospholipids. It seemed reasonable to assume that free fatty acids in the intestinal neutral lipid fraction could contribute to the increase in the permeability of p-aminobenzoic acid. On the basis of above results, possible mechanisms for good absorbability of weakly acidic drugs from the intestine are discussed.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

由于docosanol的经皮吸收有限且口服吸收不良，因此过量导致不良反应的潜力极低。治疗基本上是对症和支持性的。

Due to limited transcutaneous absorption and poor oral absorption of docosanol, the potential for an adverse reaction related to an overdose is extremely low. Treatment is essentially symptomatic and supportive.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道（如需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。密切观察呼吸不足的迹象，并在需要时辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，并在必要时进行治疗……。监测休克，并在必要时进行治疗……。预防癫痫发作，并在必要时进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用0.9%的生理盐水（NS）连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒物A和B/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

在反映正常临床使用条件下，局部吸收已被证明是最小的。

Topical absorption has been shown to be minimal under conditions reflecting normal clinical use.

来源:DrugBank

吸收、分配和排泄

多孔醇的吸收在反映正常临床使用条件下已被证明是最小的。在十名受试者连续多日测试后24小时内采集的209份血浆样本中，只有一份的孔醇水平超过了定量限（19纳克/毫升）。

Absorption of docosanol has been shown to be minimal under conditions reflecting normal clinical use. Of 209 plasma samples taken from ten subjects 24 hours after a multi-day test, only one had a docosanol level above the quantitation limits (19 nanograms/mL).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠大脑发育过程中，长链醇的含量在10天时达到最高，占总脂类的0.0109%，在40天时下降到0.0036%。它们主要由十六醇、十八醇、十八烯醇、二十醇、二十二醇和二十四醇组成。

Long chain alcohols were detected in developing rat brain at their highest level of 0.0109% of the total lipids at the age of 10 days and decreased to 0.0036% at the age of 40 days. They consited mainly of hexadecanol, octadecanol, octadecenol, eicosanol, docosanol, and tetracosanol.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

将cis-9[1(-14)C]十八碳烯醇和[1(-14)C]二十二烷醇的混合物注射到19天大的大鼠大脑中，并在3、12和24小时后测定大脑脂质中的放射性物质摄入量。这两种醇都被大脑代谢，但速率不同；每一种都被氧化成相应的脂肪酸，但油酸更容易被并入极性脂质中。大量的放射性物质被并入到乙醇胺磷脂的18:1烷基和烯基烷基部分，以及胆碱磷脂的18:1烷基部分。即使在底物混合物中18:1醇消失后（12小时），22:0醇也没有被用于可测量的烷基和烯基甘油的形成。

A mixture of cis-9[1(-14)C] octadecenol and [1(-14)C] docosanol was injected into the brains of 19-day-old rats, and incorporation of radioactivity into brain lipids was determined after 3, 12, and 24 hr. Both alcohols were metabolized by the brain but at different rates; each was oxidized to the corresponding fatty acid, but oleic acid was more readily incorporated into polar lipids. Substantial amounts of radioactivity were incorporated into 18:1 alkyl and alk-1-enyl moieties of the ethanolamine phosphoglycerides and into 18:1 alkyl moieties of the choline phosphoglycerides. Even after the disappearance of the 18:1 alcohol from the substrate mixture (12 hr), the 22:0 alcohol was not used to any measurable extent for alkyl and alk-1-enylglycerol formation.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 安全说明：
  S24/25
• WGK Germany：
  -
• 海关编码：
  29051900
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  JR1315000
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H317,H319

制备方法与用途

化学性质 1-二十二醇别名山嵛醇，是一种长碳链饱和脂肪醇。它呈现为白色固体结晶、颗粒或蜡块状，不溶于水但易溶于乙醇、乙醚、氯仿和矿物油。其熔点在68至72℃之间，沸点为180°C/0.22 mmHg。该物质的原料来源于十字花科植物种子。

毒性 这种物质表现出低毒特性：小鼠经腹膜、皮下及静脉注射的LD50均超过800 mg/kg。其急性毒性程度与食盐相当，通常对水无害。请勿未经政府许可将材料排入环境。

生物活性 Docosanol 是一种饱和脂肪酸，在化妆品中作为润肤剂、乳化剂和增稠剂使用，并且作为一种营养补充剂，能够抑制病毒产生。其ED50值为1.7 mg/ml。

用途 1-二十二醇广泛应用于个人护理、洗涤及保健用品行业，用作合成乳化剂和表面活性剂。此外，它还具有抗疱疹病毒和抗病毒的特性。

反应信息

• 作为反应物：
  描述：

  二十二烷-1-醇 在 pyridinium chlorochromate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成 (2E)-2-tetracosenoic acid
  参考文献：
  名称：

  （2 E）α，β-不饱和脂肪酸的意外的AChE抑制活性

  摘要：

  制备了一个小的（E）α，β-不饱和脂肪酸文库，并对20种链长不同的饱和和单不饱和脂肪酸进行了Ellman分析，以确定它们充当AChE或BChE抑制剂的能力。虽然这些化合物只是BChE的非常弱的抑制剂，但有7个分子是AChE的抑制剂，IC 50  = 4.3-12.8 M，其中三个是该酶的重要抑制剂。结果表明，反式2-单不饱和脂肪酸比其饱和类似物是更好的AChE抑制剂。此外，筛选结果表明链长对于获得抑制功效至关重要。对于（2 E）二十碳烯酸（图14）显示了抑制常数K i  = 1.51±0.09 M和K i '= 7.15±0.55M。所有测试的化合物均为竞争性主要成分的混合型抑制剂。分子模型计算表明活性/非活性化合物与酶AChE和BChE的结合方式不同。

  DOI：

  10.1016/j.bmcl.2018.09.013
• 作为产物：
  描述：

  二十二烷氧基二甲基苯基硅烷 在 萘 、 水 、 lithium 作用下， 生成 二十二烷-1-醇
  参考文献：
  名称：

  Reductive deprotection of allyl, benzyl and sulfonyl substituted alcohols, amines and amides using a naphthalene-catalysed lithiation

  摘要：

  The reaction of different protected alcohols, amines and amides with lithium and a catalytic amount of naphthalene (4 mol %) in THF at low temperature leads to their deprotection under very mild reaction conditions, the process being in many cases chemoselective. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)00920-4
• 作为试剂：
  描述：

  1,2-bis(5-(2-(docosyloxycarbonyl)ethyl)-3-methyl-2-thienyl)perfluorocyclopentene 在 二十二烷-1-醇 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 0.33h， 以78%的产率得到4,9-bis(2-(docosyloxycarbonyl)ethyl)-6,7-dimethyl-13,13,14,14,15,15-hexafluorotetracyclo[10.3.0.0(2,6).0(7,11)]-3,10-dithiapentadeca-1,4,8,11-tetraene
  参考文献：
  名称：

  烷基链长和氢键对2-噻吩型二芳烃在液体/高取向热解石墨（HOPG）界面上的协同自组装的影响

  摘要：

  正确理解自组装过程对于在具有功能分子的2D表面上定制纳米结构的顺序至关重要。光致变色化合物是高级光响应性表面构件的有希望的候选者。为了研究分子结构与有序形成机理之间的关系，合成了通过酰胺基或酯基连接的各种长度的烷基侧链的2-噻吩基型二蒽。通过扫描隧道显微镜（STM）研究了它们在液体/固体界面的自组装。成核平衡常数（：表面覆盖的浓度依赖性通过使用合作模式为基于两个特征参数2D表面分析ķ Ñ）和伸长率平衡常数（K e）。可以得出以下结论。1）通过STM观察到稳定的2D分子有序排列的浓度随着烷基链长度的增加呈指数下降。2）带有酰胺基的化合物比带有酯基的化合物在2D表面上具有更高的自组装性（即σ，定义为K n / K e）。3）酯衍生物的开环异构体的自组装过程接近等当性，而闭环异构体的自组装过程是协作的，因为成核步骤的平衡常数不同（即，K n）之间的两个异构体。

  DOI：

  10.1002/chem.201500707

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS ET COMPOSITIONS COMPRENANT DES INHIBITEURS DES CDK ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：UNIV GEORGIA STATE RES FOUND

  公开号：WO2010129858A1

  公开（公告）日：2010-11-11

  Disclosed herein are compounds suitable for use as antitumor agents, methods for treating cancer wherein the disclosed compounds are used in making a medicament for the treatment of cancer, methods for treating a tumor comprising, administering to a subject a composition comprising one or more of the disclosed cytotoxic agents, and methods for preparing the disclosed antitumor agents.

  本文披露了适用作抗肿瘤药剂的化合物，用于治疗癌症的方法，其中所披露的化合物用于制备治疗癌症的药物，治疗肿瘤的方法包括向受试者施用包含一种或多种所披露的细胞毒性药剂的组合物，以及制备所披露的抗肿瘤药剂的方法。
• [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)
• [EN] DERIVATIVES OF AMANITA TOXINS AND THEIR CONJUGATION TO A CELL BINDING MOLECULE<br/>[FR] DÉRIVÉS DE TOXINES D'AMANITES ET LEUR CONJUGAISON À UNE MOLÉCULE DE LIAISON CELLULAIRE
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2017046658A1

  公开（公告）日：2017-03-23

  Derivatives of Amernita toxins of Formula (I), wherein, formula (a) R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R 10, X, L, m, n and Q are defined herein. The preparation of the derivatives. The therapeutic use of the derivatives in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.

  Amernita毒素的衍生物的化学式（I），其中，化学式（a）中的R 1、R 2、R 3、R 4、R 5、R 6、R 7、R 8、R 9、R 10、X、L、m、n和Q在此处被定义。这些衍生物的制备。这些衍生物在靶向治疗癌症、自身免疫性疾病和传染病中的治疗用途。
• [EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020257998A1

  公开（公告）日：2020-12-30

  Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

  提供了一种将细胞毒性药物与一个侧链连接分子结合的共轭物。它提供了制备细胞毒性分子与细胞结合配体的共轭物的侧链连接方法，以及在靶向治疗癌症、感染和免疫性疾病中使用该共轭物的方法。

表征谱图