他扎罗汀 | 118292-40-3

• 物质功能分类: 原料药 - 专科用药 - 皮肤科用药
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 他扎罗汀
• 中文别名: 6-[2-(4,4-二甲基二氢苯并噻喃-6-基)乙炔基]吡啶-3-甲酸乙酯
• 英文名称: tazarotene
• 英文别名: ethyl 6-(2-(4,4-dimethylthiochroman-6-yl)ethynyl)nicotinate；6-[2-(3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl)ethynyl]-3-pyridinecarboxylic acid ethyl ester；ethyl 6-[2-(4,4-dimethyl-3,4-dihydro-2H-1-benzothiopyran-6-yl)ethynyl]pyridine-3-carboxylate；ethyl 6-[2-(4,4-dimethyl-2,3-dihydrothiochromen-6-yl)ethynyl]pyridine-3-carboxylate；6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinic acid ethyl ester
• CAS: 118292-40-3
• 化学式: C₂₁H₂₁NO₂S
• mdl: MFCD00867628
• 分子量: 351.469
• InChiKey: OGQICQVSFDPSEI-UHFFFAOYSA-N

物化性质

• 熔点：
  95-98°C
• 沸点：
  499.8±45.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>15mg/mL
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  64.5
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

经历皮肤酯酶水解形成其活性代谢物，他扎罗汀酸。他扎罗汀酸在皮肤中进一步代谢，并在系统吸收后，经肝脏代谢为亚砜、砜和其他极性产物以排出体外。

Undergoes esterase hydrolysis in skin to form its active metabolite, tazarotenic acid. Tazarotenic acid is further metabolized in skin and, after systemic absorption, hepatically metabolized to sulfoxides, sulfones, and other polar products for elimination.

来源:DrugBank

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间的使用总结：外用他扎罗汀在哺乳期尚未进行研究。一些专家认为，由于可能的吸收，不应在超过20%的身体表面积上使用。其他专家建议在哺乳期间不要使用，因为它具有潜在的诱变性质。如果使用他扎罗汀，请确保婴儿的皮肤不直接接触母亲已治疗的皮肤区域，并且婴儿不会从母亲的皮肤上摄入该产品。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Topical tazarotene has not been studied during breastfeeding. Some experts feel it should not be used on greater than 20% of the body surface area while nursing because of possible absorption. Others recommend that it not be used during breastfeeding because of its suspected mutagenic properties. If tazarotene is used, ensure that the infant's skin does not come into direct contact with the areas of maternal skin that have been treated and the infant does not ingest the product from the mother's skin. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 蛋白质结合

药物的有效形式是他扎罗汀酸，它高度与血浆蛋白结合（>99%）。

The active form of the drug, tazarotenic acid, is highly bound to plasma proteins (>99%).

来源:DrugBank

吸收、分配和排泄

• 吸收

塔索替尼在皮肤中迅速代谢为活性代谢物塔索替尼酸，因此系统吸收最少。塔索替尼酸可以系统吸收并进一步代谢。性别对塔索替尼酸的系统性生物利用度没有影响。

Minimal systemic absorption of tazarotene occurs due to its rapid metabolism in the skin to the active metabolite, tazarotenic acid, which can be systemically absorbed and further metabolized. Gender had no influence on the systemic bioavailability of tazarotenic acid.

来源:DrugBank

吸收、分配和排泄

• 消除途径

他扎罗汀和他扎罗汀酸被代谢成亚砜、磺酮和其他极性代谢物，通过尿液和粪便途径排出体外。

Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways.

来源:DrugBank

安全信息

• WGK Germany：
  3
• 危险品运输编号：
  NONH for all modes of transport
• 海关编码：
  2942000000
• RTECS号：
  US5675100
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  存储条件：+4℃

SDS

Tazarotene
SAFETY DATA SHEET

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Section 1. IDENTIFICATION
Product name: Tazarotene
5.3

---

Section 2. HAZARDS IDENTIFICATION
GHS classification
PHYSICAL HAZARDS Not classified
HEALTH HAZARDS
Skin corrosion/irritation Category 3
Not classified
ENVIRONMENTAL HAZARDS
GHS label elements, including precautionary statements
None
Pictograms or hazard symbols
Signal word Warning
Causes mild skin irritation
Hazard statements
Precautionary statements:
If skin irritation occurs: Get medical advice/attention.
[Response]

---

Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substance/mixture: Substance
Components: Tazarotene
Percent: >98.0%(GC)
CAS Number: 118292-40-3
C21H21NO2S
Chemical Formula:

---

Section 4. FIRST AID MEASURES
Inhalation: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
Get medical advice/attention if you feel unwell.
Skin contact: Remove/Take off immediately all contaminated clothing. Gently wash with plenty of
soap and water. If skin irritation or rash occurs: Get medical advice/attention.
Eye contact: Rinse cautiously with water for several minutes. Remove contact lenses, if present
and easy to do. Continue rinsing. If eye irritation persists: Get medical
advice/attention.
Ingestion: Get medical advice/attention if you feel unwell. Rinse mouth.
A rescuer should wear personal protective equipment, such as rubber gloves and air-
Protection of first-aiders:
tight goggles.

---

Section 5. FIRE-FIGHTING MEASURES
Suitable extinguishing Dry chemical, foam, water spray, carbon dioxide.
media:
Specific hazards arising Take care as it may decompose upon combustion or in high temperatures to
from the chemical: generate poisonous fume.
Tazarotene

---

Section 5. FIRE-FIGHTING MEASURES
Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing
method according to the surrounding situation is used. Uninvolved persons should
evacuate to a safe place. In case of fire in the surroundings: Remove movable
containers if safe to do so.
Special protective When extinguishing fire, be sure to wear personal protective equipment.
equipment for firefighters:

---

Section 6. ACCIDENTAL RELEASE MEASURES
Use personal protective equipment. Keep people away from and upwind of spill/leak.
Personal precautions,
protective equipment and Entry to non-involved personnel should be controlled around the leakage area by
emergency procedures: roping off, etc.
Environmental precautions: Prevent product from entering drains.
Methods and materials for Sweep dust to collect it into an airtight container, taking care not to disperse it.
containment and cleaning Adhered or collected material should be promptly disposed of, in accordance with
up: appropriate laws and regulations.

---

Section 7. HANDLING AND STORAGE
Precautions for safe handling
Handling is performed in a well ventilated place. Wear suitable protective equipment.
Technical measures:
Prevent dispersion of dust. Wash hands and face thoroughly after handling.
Use a local exhaust if dust or aerosol will be generated.
Advice on safe handling: Avoid contact with skin, eyes and clothing.
Conditions for safe storage, including any
incompatibilities
Storage conditions: Keep container tightly closed. Store in a refrigerator.
Store away from incompatible materials such as oxidizing agents.
Heat-sensitive
Packaging material: Comply with laws.

---

Section 8. EXPOSURE CONTROLS / PERSONAL PROTECTION
Engineering controls: Install a closed system or local exhaust as possible so that workers should not be
exposed directly. Also install safety shower and eye bath.
Personal protective equipment
Respiratory protection: Dust respirator. Follow local and national regulations.
Hand protection: Protective gloves.
Eye protection: Safety glasses. A face-shield, if the situation requires.
Skin and body protection: Protective clothing. Protective boots, if the situation requires.

---

Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Solid
Physical state (20°C):
Form: Crystal- Powder
Colour: Very pale yellow - Yellow
No data available
Odour:
pH: No data available
Melting point/freezing point:105°C
Boiling point/range: No data available
No data available
Flash point:
Flammability or explosive
limits:
Lower: No data available
No data available
Upper:
Relative density: No data available
Solubility(ies):
[Water] No data available
No data available
[Other solvents]
Log Pow: 5.25
Tazarotene

---

Section 10. STABILITY AND REACTIVITY
Chemical stability: Stable under proper conditions.
Possibility of hazardous No special reactivity has been reported.
reactions:
Incompatible materials: Oxidizing agents
Hazardous decomposition Carbon monoxide, Carbon dioxide, Nitrogen oxides (NOx), Sulfur oxides
products:

---

Section 11. TOXICOLOGICAL INFORMATION
Acute Toxicity: orl-rat LD:>2 g/kg
Skin corrosion/irritation: skn-hmn 0.1%/12W-I open
Serious eye No data available
damage/irritation:
Germ cell mutagenicity: No data available
Carcinogenicity:
IARC = No data available
No data available
NTP =
Reproductive toxicity: No data available
US5675100
RTECS Number:

---

Section 12. ECOLOGICAL INFORMATION
Ecotoxicity:
Fish: No data available
Crustacea: No data available
Algae: No data available
Persistence / degradability: No data available
Bioaccumulative No data available
potential(BCF):
Mobility in soil
Log Pow: 5.25
Soil adsorption (Koc): No data available
Henry's Law No data available
constant(PaM3/mol):

---

Section 13. DISPOSAL CONSIDERATIONS
Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material
with a 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.

---

Section 14. TRANSPORT INFORMATION
Hazards Class: Does not correspond to the classification standard of the United Nations
UN-No: Not listed

---

Section 15. REGULATORY INFORMATION
Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002
and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport,
loading and unloading were prescribed.
Tazarotene

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

皮肤科用药 他扎罗汀

他扎罗汀是第三代维甲酸类皮肤科用药，为皮肤外用的类维生素A前体药。它具有调节表皮细胞分化和增殖的作用，主要适用于治疗斑块型寻常性银屑病，并可用于治疗面部痤疮。

临床使用时，每晚临睡前半小时将适量15mg/30g他扎罗汀乳膏涂于患处。用药前先清洗患处，待皮肤干燥后均匀涂抹药物，形成一层薄膜并轻轻揉擦以促进吸收。豌豆大小的凝胶可以覆盖手掌大面积的皮损，但涂抹面积不能超过体表面积的20%。

银屑病

银屑病是一种常见的良性、急性或慢性炎症性皮肤病。在遗传倾向的基础上发生，在某些情况下，外伤或刺激可诱发银屑病皮损（Koebner现象）。最常见的是斑块型银屑病；发疹型（点滴型）银屑病包括许多3～10mm的皮损，偶尔发生在精神紧张或链球菌咽炎之后。在严重的情况下，可能会出现泛发性脓疱型和红皮病型银屑病。

他扎罗汀凝胶

他扎罗汀凝胶为外用甲酸制剂，用于治疗银屑病。研究显示每日两次使用八周后约50%轻至中度银屑病患者至少75%的皮损可获缓解。tazarotene凝胶有0.05%和0.1%两种浓度，0.1%凝胶外用一日一次与二日一次的效果无明显差异，但0.5%凝胶外用一日一次效果较差。

他扎罗汀是一种合成的乙烯视黄醛。局部用药后快速转化为他扎罗汀酸发挥作用。他扎罗汀酸与皮肤中的RAR-γ受体结合，可能通过恢复正常的皮肤分化和减少皮肤炎症改善临床症状。

不良反应及注意事项

不良反应： 主要为皮肤反应，如瘙痒、灼热感、刺痛感、红斑、刺激感、皮肤疼痛、脱屑、皮炎、皲裂、水肿、脱色、出血和干燥等。

注意事项：

1. 育龄妇女在开始治疗前2周内需进行血清或尿液妊娠试验，确保结果为阴性后，在下次正常月经周期的第2天或第3天开始治疗。治疗期间及停药一段时间内必须使用有效的避孕措施。
2. 避免药物与眼睛、口腔和黏膜接触，并尽量避免药物与正常皮肤接触。如与眼接触，应立即用清水彻底冲洗。
3. 如出现瘙痒等皮肤刺激作用，尽量不要搔抓，可涂少量润肤剂；严重时应停药或隔天使用一次。
4. 本品不宜用于急性湿疹类皮肤病。
5. 治疗期间避免在阳光下过多暴露，并避免同时服用光敏药物。
6. 涂药后不应包扎患处，避免同时使用能使皮肤变干燥的药品和化妆品。涂抹面积超过体表面积20%时需谨慎。
7. 具有妊娠毒性，孕妇应禁用。

体内研究

他扎罗汀在UV-和电离辐射处理的Ptcb+/−小鼠中治疗可减少周围基底细胞癌的数量和大小。

化学性质

类白色或淡黄色固体。

反应信息

• 作为反应物：
  描述：

  他扎罗汀 在 过氧化苯甲酰 作用下， 生成 过氧化苯甲酰
  参考文献：
  名称：

  Benzoyl Peroxide Composition, Methods for Making Same, and Pharmaceutical or Cosmetic Formulations Comprising Same, and Uses Thereof

  摘要：

  本发明涉及制备包含过氧苯甲酰的组合物，可包含其他额外活性成分。该过程涉及将过氧苯甲酰以及其他任何活性成分引入含有并保护这些成分的脂肪物质中，以防止它们在接触时变得不稳定。该组合物设计为在脂肪物质软化和/或融化时，使所有成分可用于皮肤接触或皮肤吸收。过氧苯甲酰可以经预微粒化处理，粒度分布大小约为d90的0.1至150微米，优选d90的10至15微米。此外，医药或化妆品成分可以包含在脂肪物质中，其中可能含有或不含有过氧苯甲酰，或者可能存在于脂肪物质之外，但在使用脂肪物质保护的活性成分的制剂医药或化妆品产品中的其他地方。这些组合物可用于治疗疾病的水基配方，通过局部、经皮和/或皮下给药。

  公开号：

  US20120064135A1
• 作为产物：
  描述：

  6-乙炔基-4,4-二甲基二氢苯并噻喃 在 四(三苯基膦)钯 、 三苯基膦 copper(l) iodide 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 他扎罗汀
  参考文献：
  名称：

  WO2006/59345

  摘要：

  公开号：

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] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2017012647A1

  公开（公告）日：2017-01-26

  The present invention discloses compounds according to Formula (I), wherein R1, R3, R4, R5, L1, and Cy are as defined herein. The present invention also provides compounds, methods for the production of said compounds of the invention, pharmaceutical compositions comprising the same and their use in allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 and/or interferons. The present invention also methods for the prevention and/or treatment of the aforementioned diseases by administering a compound of the invention.

  本发明公开了根据式（I）的化合物，其中R1、R3、R4、R5、L1和Cy如本文所定义。本发明还提供了该发明的化合物、制备该化合物的方法、包括相同化合物的药物组合物以及它们在过敏或炎症症状、自身免疫疾病、增殖性疾病、移植排斥、涉及软骨周转障碍的疾病、先天软骨畸形和/或与IL6和/或干扰素过度分泌相关的疾病中的使用。本发明还提供了通过给予该发明的化合物来预防和/或治疗上述疾病的方法。
• New Drug Delivery System for Crossing the Blood Brain Barrier
  申请人：Lipshutz H. Bruce

  公开号：US20070203080A1

  公开（公告）日：2007-08-30

  New ubiquinol analogs are disclosed, as well as methods of using these compounds to deliver drug moieties to the body.

  新的泛醌类似物被披露，以及利用这些化合物将药物基团输送到人体的方法。
• [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)