盐酸吉西他滨 | 122111-03-9

• 物质功能分类: 原料药 - 抗肿瘤药 - 抗代谢类抗肿瘤药
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 盐酸吉西他滨
• 中文别名: 盐酸吉西他宾；4-氨基-1-(3,3-二氟-4-羟基-5-羟甲基四氢呋喃-2-基)-1H-嘧啶-2-酮盐酸盐；吉西他宾盐酸盐；吉西他滨盐酸盐；注射用盐酸吉西他滨；(+)2'-脱氧-2'2'-二氟胞嘧啶
• 英文名称: gemcitabine hydrochloride
• 英文别名: Gemzar；2',2'-difluoro-2'-deoxycytidine hydrochloride；2'-deoxy-2',2'-difluorocytidine hydrochloride；gemcitabine HCl；2'-deoxy-2',2'-difluorocytidine monohydrochloride；2',2'-difluorodeoxycytidine hydrochloride；[1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]azanium;chloride；6-amino-3-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-pyrimidin-3-ium-2-one;chloride
• CAS: 122111-03-9
• 化学式: C₉H₁₁F₂N₃O₄*ClH
• 分子量: 299.662
• InChiKey: OKKDEIYWILRZIA-OSZBKLCCSA-N

物化性质

• 熔点：
  >250°C dec.
• 比旋光度：
  D +48°; 365 +257.9° (c = 1.0 in deuterated water)
• 溶解度：
  H2O：≥10mg/mL
• 最大波长(λmax)：
  268nm(H2O)(lit.)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.87
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  6

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：大多数来源认为，在母亲抗肿瘤药物治疗期间，母乳喂养是禁忌的。在间歇性吉西他滨治疗期间，如果有一个适当的禁乳期，可能可以安全地进行母乳喂养；制造商建议在最后一次给药后至少禁乳1周。化疗可能会不利地影响母乳的正常微生物组和化学成分。[1] 在怀孕期间接受化疗的妇女更有可能在哺乳婴儿时遇到困难。[2] ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关已发布信息。 ◉ 对泌乳和母乳的影响：对74名在怀孕第二或第三季度在一个中心接受癌症化疗的妇女进行了电话随访研究，以确定她们产后是否成功进行母乳喂养。只有34%的妇女能够完全用母乳喂养她们的婴儿，而66%的妇女报告遇到母乳喂养困难。这与22位在怀孕期间被诊断出患有癌症但未接受化疗的母亲91%的母乳喂养成功率形成了对比。其他具有统计学意义的关联包括：1. 有母乳喂养困难的母亲平均接受了5.5个周期的化疗，而没有困难的母亲平均接受了3.8个周期；2. 有母乳喂养困难的母亲在怀孕期间平均提前3.4周接受了第一个周期的化疗。在接受含有氟尿嘧啶方案的9名妇女中，有8名遇到了母乳喂养困难。[2]

◉ Summary of Use during Lactation:Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. It might be possible to breastfeed safely during intermittent gemcitabine therapy with an appropriate period of breastfeeding abstinence; the manufacturer recommends an abstinence period of at least 1 week after the last dose. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk.[1] Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.[2] ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 9 women who received a fluorouracil-containing regimen, 8 had breastfeeding difficulties.[2]

来源:Drugs and Lactation Database (LactMed)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S25,S26,S36/37,S53
• 危险类别码：
  R21
• WGK Germany：
  3
• 海关编码：
  2934999090
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  HA3840000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  Desiccate at 4°C

SDS

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Section I.Chemical Product and Company Identification
Chemical Name Gemcitabine Hydrochloride
Portland OR
Synonym Cytidine, 2'-deoxy-2',2'-difluoro-, hydrochloride (1:1)
(CA INDEX NAME)
Chemical Formula C9H11F2N3O4 · HCl
CAS Number 122111-03-9

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Section II. Composition and Information on Ingredients
Toxicology Data
Chemical Name CAS Number Percent (%) TLV/PEL
Min. 98.0 Not available. Rat LD50 (intravenous) 236 mg/kg
Gemcitabine Hydrochloride 122111-03-9
(HPLC,N) Mouse LD50 (intravenous) 500
mg/kg

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Section III. Hazards Identification
Irritating to eyes and skin on contact. Inhalation causes irritation of the lungs and respiratory system. Inflammation of the
Acute Health Effects
eye is characterized by redness, watering, and itching. Skin inflammation is characterized by itching, scaling, reddening, or,
occasionally, blistering.
Follow safe industrial hygiene practices and always wear proper protective equipment when handling this compound.
CARCINOGENIC EFFECTS : Not available.
Chronic Health Effects
MUTAGENIC EFFECTS : Not available.
TERATOGENIC EFFECTS : Not available.
DEVELOPMENTAL TOXICITY: Reproductive effects.
Mouse TDLo Intravenous 15 mg/kg, female 6-15 days of pregnancy
Toxic Effects:
Maternal Effects - Parturition
Effects on Fertility - Post-implantation mortality
Effects on Fertility - Litter size
Mouse TDLo Intravenous 15 mg/kg, female 6-15 days of pregnancy
Toxic Effects:
Maternal Effects - Other effects
Effects on Embryo or Fetus - Fetotoxicity
Effects on Embryo or Fetus - Fetal death
Repeated or prolonged exposure to this compound is not known to aggravate existing medical conditions.

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Section IV. First Aid Measures
Eye Contact Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at least 15
minutes. Get medical attention.
Skin Contact In case of contact, immediately flush skin with plenty of water. Remove contaminated clothing and shoes. Wash clothing
before reuse. Thoroughly clean shoes before reuse. Get medical attention.
If the victim is not breathing, perform mouth-to-mouth resuscitation. Loosen tight clothing such as a collar, tie, belt or
Inhalation
waistband. If breathing is difficult, oxygen can be administered. Seek medical attention if respiration problems do not
improve.
INDUCE VOMITING by sticking finger in throat. Lower the head so that the vomit will not reenter the mouth and throat.
Ingestion
Loosen tight clothing such as a collar, tie, belt or waistband. If the victim is not breathing, perform mouth-to-mouth
resuscitation. Examine the lips and mouth to ascertain whether the tissues are damaged, a possible indication that the toxic
material was ingested; the absence of such signs, however, is not conclusive.

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Section V. Fire and Explosion Data
Not available.
May be combustible at high temperature. Auto-Ignition
Flammability
Flash Points Flammable Limits Not available.
Not available.
These products are toxic carbon oxides (CO, CO2), nitrogen oxides (NO, NO2), halogenated compounds.
Combustion Products
WARNING: Highly toxic HCl gas is produced during combustion.
WARNING: Highly toxic HF gas is produced during combustion.
Fire Hazards
Not available.
Continued on Next Page
Gemcitabine Hydrochloride
Explosion Hazards Risks of explosion of the product in presence of mechanical impact: Not available.
Risks of explosion of the product in presence of static discharge: Not available.
Fire Fighting Media SMALL FIRE: Use DRY chemical powder.
LARGE FIRE: Use water spray, fog or foam. DO NOT use water jet.
and Instructions
Consult with local fire authorities before attempting large scale fire-fighting operations.

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Section VI. Accidental Release Measures
Spill Cleanup Irritating material. This material is a reproductive effector.
Use a shovel to put the material into a convenient waste disposal container. Consult federal, state, and/or local authorities for
Instructions
assistance on disposal.

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Section VII. Handling and Storage
IRRITANT. REPRODUCTIVE EFFECTOR. Keep away from heat. Mechanical exhaust required. When not in use, tightly
Handling and Storage
seal the container and store in a dry, cool place. Avoid excessive heat and light. Do not breathe dust.
Information
Always store away from incompatible compounds such as oxidizing agents.

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Section VIII. Exposure Controls/Personal Protection
Engineering Controls Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below recommended
exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to airborne contaminants
below the exposure limit.
Personal Protection Splash goggles. Lab coat. Dust respirator. Boots. Gloves. Suggested protective clothing might not be sufficient; consult a
specialist BEFORE handling this product. Be sure to use a MSHA/NIOSH approved respirator or equivalent.
Not available.
Exposure Limits

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Section IX. Physical and Chemical Properties
Physical state @ 20°C Solid. (White crystalline powder.) Solubility Soluble in hot water.
Not available.
Specific Gravity
Molecular Weight 299.66 Partition Coefficient Not available.
Boiling Point Not available. Not applicable.
Vapor Pressure
Melting Point 287 to 292°C (548.6 to 557.6°F) (dec.) Vapor Density Not available.
Not available. Not available.
Refractive Index Volatility
Critical Temperature Not available. Odor Not available.
Not available. Not available.
Viscosity Taste

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Section X. Stability and Reactivity Data

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This material is stable if stored under proper conditions. (See Section VII for instructions)
Stability
Conditions of Instability Avoid excessive heat and light.
Incompatibilities Reactive with oxidizing agents.

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Section XI. Toxicological Information
RTECS Number HA3840000
Eye Contact. Ingestion. Inhalation.
Routes of Exposure
Rat LD50 (intravenous) 236 mg/kg
Toxicity Data
Mouse LD50 (intravenous) 500 mg/kg
CARCINOGENIC EFFECTS : Not available.
Chronic Toxic Effects
MUTAGENIC EFFECTS : Not available.
TERATOGENIC EFFECTS : Not available.
DEVELOPMENTAL TOXICITY: Reproductive effects.
Mouse TDLo Intravenous 15 mg/kg, female 6-15 days of pregnancy
Toxic Effects:
Maternal Effects - Parturition
Effects on Fertility - Post-implantation mortality
Effects on Fertility - Litter size
Mouse TDLo Intravenous 15 mg/kg, female 6-15 days of pregnancy
Toxic Effects:
Maternal Effects - Other effects
Effects on Embryo or Fetus - Fetotoxicity
Effects on Embryo or Fetus - Fetal death
Repeated or prolonged exposure to this compound is not known to aggravate existing medical conditions.
Continued on Next Page
Gemcitabine Hydrochloride
Acute Toxic Effects Irritating to eyes and skin on contact. Inhalation causes irritation of the lungs and respiratory system. Inflammation of the eye
is characterized by redness, watering, and itching. Skin inflammation is characterized by itching, scaling, reddening, or,
occasionally, blistering.
Follow safe industrial hygiene practices and always wear proper protective equipment when handling this compound.

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Section XII. Ecological Information
Not available.
Ecotoxicity
Environmental Fate Not available.

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Section XIII. Disposal Considerations
Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material with a
Waste Disposal
combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system. Observe all
federal, state and local regulations when disposing of the substance.

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Section XIV. Transport Information
DOT Classification Not a DOT controlled material (United States).
PIN Number Not applicable.
Proper Shipping Name Not applicable.
Packing Group (PG) Not applicable.
DOT Pictograms

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Section XV. Other Regulatory Information and Pictograms
TSCA Chemical Inventory This product is NOT on the EPA Toxic Substances Control Act (TSCA) inventory. The following notices are required by 40
CFR 720.36 (C) for those products not on the inventory list:
(EPA)
(i) These products are supplied solely for use in research and development by or under the supervision of a technically
qualified individual as defined in 40 CFR 720.0 et sec.
(ii) The health risks of these products have not been fully determined. Any information that is or becomes available will be
supplied on an MSDS sheet.
WHMIS Classification Not available.
(Canada)
EINECS Number (EEC) 601-823-3
EEC Risk Statements R36/37/38- Irritating to eyes, respiratory system and skin.
R60- May impair fertility.
R61- May cause harm to the unborn child.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

盐酸吉西他滨是一种人工合成的新型二氟核苷类抗代谢抗肿瘤药，由礼来公司研制开发，并于1995年在南非、瑞典、荷兰、澳大利亚等国家获准上市。1996年，美国食品药物管理局（FDA）批准其用于非小细胞肺癌和胰腺癌的一线治疗。国内主要生产盐酸吉西他滨的厂家有江苏豪森药业股份有限公司和哈尔滨誉衡药业公司。

作为一种前药，盐酸吉西他滨在细胞内被脱氧胸苷激酶磷酸化为良好的底物，转化成吉西他滨－磷酸盐（dFdCMP）、吉西他滨二磷酸盐（dFdCDP）和吉西他滨三磷酸盐（dFdCTP），其中后二者为活性产物。近年来，如吉西他滨、紫杉醇、多西紫杉醇、异长春花碱等新型药物在治疗非小细胞肺癌(简称NSCLC)中表现出较高疗效和较低毒性。

作为新一代抗代谢药，盐酸吉西他滨是细胞周期特异性药物，主要作用于DNA合成期（S期）。国外研究显示，在单用或联合顺铂、卡铂治疗NSCLC时，其有效率分别为18%～35%和41.7%，疗效与顺铂相似但毒性较低。

鉴别

(1) 取盐酸吉西他滨适量，加水制成每1ml中含10μg的溶液，用分光光度法测定，在269nm波长处有最大吸收，在249nm波长处有最小吸收。 (2) 在含量测定过程中，与标准品比较，进行鉴别。 (3) 采用高效液相色谱法对盐酸吉西他滨进行定量分析，对照品溶液和供试品溶液的峰面积应一致。

生物活性

Gemcitabine HCl (LY188011) 是一种DNA合成抑制剂，作用于PANC1、MIAPaCa2、BxPC3 和Capan2细胞，其IC50值分别为50 nM、40 nM、18 nM和12 nM。

靶点

Target	Value
DNA synthesis (Capan2 cells)	12 nM
DNA synthesis (BxPC3 cells)	18 nM
DNA synthesis (MIAPaCa2 cells)	40 nM
DNA synthesis (PANC1 cells)	50 nM

体外研究

Gemcitabine作用于BxPC-3, PANC-1, 和MIA PaCa-2细胞，诱导NF-κB活性。在低剂量处理BxPC-3和PANC-1细胞48小时后，降低IκBα水平，并提高NF-κB结合；而在更高剂量下，则相反。

体内研究

与PBS处理的小鼠相比，Gemcitabine处理的小鼠瘤内NF-κB活性显著提高（提高1.3-到1.8-倍）。

用途

适用于治疗不能手术的晚期或转移性胰腺癌及局部进展性或转移性非小细胞肺癌。此外，还用于中、晚期非小细胞肺癌、胰腺癌、膀胱癌、乳腺癌及其他实体肿瘤的治疗。

反应信息

• 作为反应物：
  描述：

  盐酸吉西他滨 在 水 、 溴 、 四丁基溴化铵 、 N,N-二异丙基乙胺 作用下， 以 正己烷 为溶剂， 反应 2.0h， 以70.8%的产率得到4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-hydroxymethyltetrahydrofuran-2-yl)-5-hydroxypyrimidine-2(1H)-one
  参考文献：
  名称：

  一种盐酸吉西他滨氧化杂质的制备方法

  摘要：

  本发明提供了一种盐酸吉西他滨氧化杂质的制备方法，包括如下步骤：以盐酸吉西他滨为起始原料，依次经过溴代反应和水解反应，得到氧化杂质(1)。本发明的优点在于：所用试剂简单易得，合成路线简短，操作简单，收率较高，所得杂质产物的纯度较高(HPLC纯度99％以上)，可应用于对照品研究。

  公开号：

  CN108484704A
• 作为产物：
  描述：

  gemcitabine hydrochloride 以 水 、 异丙醇 为溶剂， 反应 2.0h， 生成 盐酸吉西他滨
  参考文献：
  名称：

  WO2007/112473

  摘要：

  公开号：
• 作为试剂：
  描述：

  盐酸吉西他滨 、 氯化钠 在 盐酸吉西他滨 作用下， 生成 吉西他滨
  参考文献：
  名称：

  USES OF IL-12 IN HEMATOPOIETIC IMMUNOTHERAPY (HIT)

  摘要：

  本公开的方面和实施例提供了治疗方法和组合物，包括白细胞介素12（IL-12）作为造血免疫治疗（HIT），用于治疗或预防癌症患者因化疗引起的细胞减少需要剂量减少和/或剂量延迟。在患者接受化疗药物后，该方法包括：向受试者注射包含基本分离的IL-12的治疗有效量的药物组合物，从而减少细胞减少，并导致对化疗药物的反应减弱。

  公开号：

  US20160120949A1

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。
• Eflornithine Prodrugs, Conjugates and Salts, and Methods of Use Thereof
  申请人：Xu Feng

  公开号：US20100120727A1

  公开（公告）日：2010-05-13

  In one aspect, the present invention provides a composition of a covalent conjugate of an eflornithine analog with an anti-inflammatory drug. In another aspect, the present invention provides a composition of an eflornithine prodrug. In another aspect, the present invention provides a composition of an eflornithine or its derivatives aspirin salt. In another aspect, the present invention provides methods for treating or preventing cancer using the conjugates or salts of eflornithine analogs or eflornithine prodrugs.

  在一个方面，本发明提供了一种氟硝西汀类似物与抗炎药物的共价结合物的组合物。在另一个方面，本发明提供了一种氟硝西汀前药的组合物。在另一个方面，本发明提供了一种氟硝西汀或其衍生物水杨酸盐的组合物。在另一个方面，本发明提供了使用氟硝西汀类似物或氟硝西汀前药的共轭物或盐来治疗或预防癌症的方法。
• [EN] METALLOENZYME INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE MÉTALLOENZYMES
  申请人：VPS 3 INC

  公开号：WO2018165520A1

  公开（公告）日：2018-09-13

  Provided are compounds having HDAC6 modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by HDAC6.

  提供具有HDAC6调节活性的化合物，以及通过HDAC6介导的治疗疾病、疾病或症状的方法。
• [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)