依匹斯汀 | 80012-43-7

• 物质功能分类: 原料药 - 抗变态反应药 - 抗组胺药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: 依匹斯汀
• 中文别名: 依匹斯汀碱；3-氨基-9,13-二氢-1H-二苯并[c,f]咪唑并[1,5-a]氮杂卓
• 英文名称: epinastine
• 英文别名: 3-amino-9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5-a]azepine；3-amino-9,13b-dihydro-1H-dibenz[c,f]imidazo[1,5-a]azepine；2,4-diazatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),3,7,9,11,14,16-heptaen-3-amine
• CAS: 80012-43-7
• 化学式: C₁₆H₁₅N₃
• mdl: MFCD00865648
• 分子量: 249.315
• InChiKey: WHWZLSFABNNENI-UHFFFAOYSA-N

物化性质

• 熔点：
  205-208°
• 沸点：
  428.0±55.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：≥ 50 mg/mL (200.55 mM)；水：< 0.1 mg/mL（不溶）
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.187
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

主要以原形排泄，小于10%被代谢。

Mainly excreted unchanged, less than 10% metabolized.

来源:DrugBank

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：来自7个个体的证据表明，艾普拉司丁进入母乳和随后导致的婴儿血清水平可能是最低限度的，不太可能在母乳喂养的婴儿中引起不良反应。在美国，艾普拉司丁仅以眼药水形式提供。由于眼部吸收有限，艾普拉司丁不会预期在母乳喂养的婴儿中引起任何不良反应。为了显著减少使用眼药水后到达母乳中的药物量，可以在眼角处对泪囊施加压力1分钟或更长时间，然后用吸收性纸巾去除多余的溶液。 ◉ 对母乳喂养婴儿的影响：在一项对7位每日口服艾普拉司丁20毫克母乳喂养母亲的研究中，没有报告婴儿出现不良反应。 ◉ 对泌乳和母乳的影响：在非哺乳期妇女和产后期妇女中，通过注射给予相对高剂量的抗组胺药可以降低基础血清催乳素。然而，吮吸诱导的催乳素分泌不会受到产后母亲抗组胺药预处理的影响。已建立泌乳的母亲催乳素水平可能不会影响她的哺乳能力。低剂量的艾普拉司丁眼药水不太可能对血清催乳素有同样的影响。

◉ Summary of Use during Lactation:Evidence from 7 individuals indicates that transfer of epinastine into breastmilk and the resulting infant serum levels are likely to be minimal and unlikely to cause adverse effects in breastfed infants. In the U.S., epinastine is only available as eye drops. Because absorption from the eye is limited, epinastine would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue. ◉ Effects in Breastfed Infants:In a study of 7 nursing mothers who were taking oral epinastine 20 mg once daily. No adverse reactions in the infants were reported. ◉ Effects on Lactation and Breastmilk:Antihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women. However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. Low ophthalmic doses of epinastine are unlikely to have the same effect on serum prolactin.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 蛋白质结合

百分之六十四

64%

来源:DrugBank

吸收、分配和排泄

• 吸收

盐酸依匹那汀的绝对生物利用度约为40%。

The absolute bioavailability of epinastine is about 40%.

来源:DrugBank

吸收、分配和排泄

• 消除途径

依匹那汀主要不经改变地排出。肾消除主要是通过积极的管分泌。

Epinastine is mainly excreted unchanged. The renal elimination is mainly via active tubular secretion.

来源:DrugBank

吸收、分配和排泄

• 清除

每分钟4滴 [对过敏性结膜炎患者每天两次，每次每眼一滴，使用ELESTAT®眼药水，持续七天]

56 L/hr [patients with allergic conjunctivitis receiving one drop of ELESTAT® ophthalmic solution in each eye twice daily for seven days]

来源:DrugBank

安全信息

• 包装等级：
  III
• 危险类别：
  9
• 危险性防范说明：
  P501,P273,P260,P270,P264,P280,P391,P314,P337+P313,P305+P351+P338,P301+P312+P330
• 危险品运输编号：
  3077
• 危险性描述：
  H302,H319,H372,H410
• 储存条件：
  | 2-8℃ |

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: Epinastine
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: Epinastine
CAS number: 80012-43-7

---

Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

---

Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

---

Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

---

Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

---

Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

---

Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C16H15N3
Molecular weight: 249.3

---

Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Epinastine (WAL801) 是一种抗组胺剂和肥大细胞稳定剂。它是一种有效的、选择性的、口服活性的组胺 H1 受体拮抗剂，还能抑制 IL-8 的释放并具有抗过敏作用。

体外研究

Epinastine 能在低浓度下置换蝗虫神经组织中的特定 [3H]NC-5Z 结合。它还与蜜蜂神经多巴胺受体结合，其 Ki 值为 1.1 nM，并能对抗多巴胺诱导的昆虫大脑中 cAMP 的生成。

Epinastine 能抑制由抗原抗体反应和化合物 48/80 引起的大鼠腹膜肥大细胞中的组胺释放。它同样在孤立的大鼠腹膜肥大细胞及大鼠肠系膜片中有效抑制由化合物 48/80 和物质 P 触发的组胺释放。Epinastine 还能抑制活性致敏豚鼠肺部肥大细胞中的钙离子摄入，并且在暴露于化合物 48/80 和物质 P 的大鼠腹膜肥大细胞中，有效抑制钙离子从细胞内钙库的释放。

此外，Epinastine 在体外对从过敏性疾病中分离出的嗜酸性粒细胞中以剂量和时间依赖的方式抑制白介素-8 (IL-8) 的释放，这是一种嗜酸性粒细胞趋化因子。

体内研究

在豚鼠回肠受体结合研究中，Epinastine 显示出对 H1 受体的高亲和力。它能抑制由大鼠、狗和豚鼠引起的组胺诱导反应。

反应信息

• 作为反应物：
  描述：

  依匹斯汀 在 溴 作用下， 以 氯仿 为溶剂， 反应 10.0h， 以46%的产率得到7-溴依匹斯汀
  参考文献：
  名称：

  一种盐酸依匹斯汀杂质B的合成方法

  摘要：

  本发明涉及医药技术领域，尤其涉及一种盐酸依匹斯汀杂质的制备方法。本发明首先以6‑(邻苯二甲酰亚胺基甲基)‑6,11‑二氢‑5H‑二苯并‑[b,e]氮杂为起始原料，用水合肼脱去保护基，再与溴化氰关环得到3‑氨基‑9,13‑二氢‑1H‑二苯并[c,f]‑咪唑并[1,5‑a]氮杂(依匹斯汀)，最后与溴单质反应制得盐酸依匹斯汀杂质B。本发明盐酸依匹斯汀杂质B的合成方法，工艺路线简单，操作方便，选择性好，收率高；合成的盐酸依匹斯汀杂质B可作为盐酸依匹斯汀的有关物质检测用对照品，用于盐酸依匹斯汀及其相关制剂的质量控制的应用，控制盐酸依匹斯汀原料药或者其制剂的纯度。

  公开号：

  CN107118216B
• 作为产物：
  描述：

  6-(邻苯二甲酰亚胺基甲基)-6,11-二氢-5H-二苯并-[b,e]氮杂卓 在 一水合肼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 依匹斯汀
  参考文献：
  名称：

  一种盐酸依匹斯汀杂质B的合成方法

  摘要：

  本发明涉及医药技术领域，尤其涉及一种盐酸依匹斯汀杂质的制备方法。本发明首先以6‑(邻苯二甲酰亚胺基甲基)‑6,11‑二氢‑5H‑二苯并‑[b,e]氮杂为起始原料，用水合肼脱去保护基，再与溴化氰关环得到3‑氨基‑9,13‑二氢‑1H‑二苯并[c,f]‑咪唑并[1,5‑a]氮杂(依匹斯汀)，最后与溴单质反应制得盐酸依匹斯汀杂质B。本发明盐酸依匹斯汀杂质B的合成方法，工艺路线简单，操作方便，选择性好，收率高；合成的盐酸依匹斯汀杂质B可作为盐酸依匹斯汀的有关物质检测用对照品，用于盐酸依匹斯汀及其相关制剂的质量控制的应用，控制盐酸依匹斯汀原料药或者其制剂的纯度。

  公开号：

  CN107118216B

文献信息

• Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20150231142A1

  公开（公告）日：2015-08-20

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及含有上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。
• [EN] PYRIMIDINE JAK INHIBITORS FOR THE TREATMENT OF SKIN DISEASES<br/>[FR] INHIBITEURS DE JAK À BASE DE PYRIMIDINE POUR LE TRAITEMENT DE MALADIES DE LA PEAU
  申请人：THERAVANCE BIOPHARMA R&D IP LLC

  公开号：WO2020219640A1

  公开（公告）日：2020-10-29

  The invention provides compounds of formula (I): or pharmaceutically-acceptable salts thereof, that are inhibitors of Janus kinases. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat inflammatory and autoimmune skin diseases.

  该发明提供了式(I)的化合物或其药用可接受盐，这些化合物是Janus激酶的抑制剂。该发明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治疗炎症性和自身免疫性皮肤疾病的方法。
• 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。
• Imidazole and benzimidazole derivatives useful as histamine H3 antagonists
  申请人：Aslanian G. Robert

  公开号：US20060166960A1

  公开（公告）日：2006-07-27

  Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: n is 2-5; R is R 3 -aryl, R 3 -heteroaryl, R 3 -cycloalkyl, R 3 -heterocycloalkyl, alkyl, haloalkyl, —OR 4 , —SR 4 or —S(O) 1-2 R 5 ; R 1 and R 2 are H or optionally substituted phenyl or optionally substituted and X is —O— or —S—; or R 1 and R 2 , together with the carbon atoms to which they are attached form optionally substituted and X is —O—, —S— or —NR 7 —; Z is and the remaining variables are as defined in the specification; also disclosed are pharmaceutical compositions comprising the compounds of formula I; also disclosed are methods of treating allergy, allergy-induced airway responses, congestion, obesity and metabolic syndrome using the compounds of Formula I, as well as combinations with other drugs useful for treating those diseases.

  揭示了以下公式化合物或其药学上可接受的盐或溶剂，其中：n为2-5；R为R3-芳基，R3-杂环芳基，R3-环烷基，R3-杂环烷基，烷基，卤代烷基，—OR4，—SR4或—S(O)1-2R5；R1和R2为H或可选择地取代的苯基或可选择地取代的，X为—O—或—S—；或R1和R2，连同它们连接的碳原子形成可选择地取代的，X为—O—，—S—或—NR7—；Z为，其余变量如规范中所定义；还揭示了包括公式I化合物的药物组合物；还揭示了使用公式I化合物治疗过敏、过敏引起的气道反应、充血、肥胖和代谢综合征的方法，以及与其他用于治疗这些疾病的药物的组合。
• [EN] 1-(4-PIPERIDINYL) BENZIMIDAZOLONES AS HISTAMINE H3 ANTAGONISTS<br/>[FR] 1-(4-PIPERIDINYL) BENZIMIDAZOLONES UTILISES EN TANT QU'ANTAGONISTES DU RECEPTEUR H3 DE L'HISTAMINE
  申请人：SCHERING CORP

  公开号：WO2003103669A1

  公开（公告）日：2003-12-18

  Disclosed are histamine H3 antagonists of the formula (I) wherein R1 is benzimidazolone derivative, M1 and M2 are optionally substituted carbon or nitrogen, R2 includes optionally substituted aryl or heteroaryl, and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula (I). Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula (I). Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of formula (I) in combination with a H1 receptor antagonist.

  揭示了公式（I）中的组胺H3拮抗剂，其中R1是苯并咪唑酮衍生物，M1和M2是可选择地取代的碳或氮，R2包括可选择地取代的芳基或杂环基，其余变量如规范中所定义。还揭示了包括公式（I）化合物的药物组合物。还揭示了使用公式（I）化合物治疗各种疾病或症状的方法，例如过敏、过敏引起的气道反应和充血（例如，鼻塞）的方法。还揭示了使用公式（I）化合物与H1受体拮抗剂结合治疗各种疾病或症状的方法，例如过敏、过敏引起的气道反应和充血（例如，鼻塞）。