甲磺酸厄洛替尼 | 248594-19-6

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 甲磺酸厄洛替尼
• 英文名称: N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine, methanesulfonic acid salt
• 英文别名: N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine mesylate；Erlotinib mesylate；N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine;methanesulfonic acid
• CAS: 248594-19-6
• 化学式: CH₄O₃S*C₂₂H₂₃N₃O₄
• 分子量: 489.549
• InChiKey: PCBNMUVSOAYYIH-UHFFFAOYSA-N

物化性质

• 溶解度：
  25℃：二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.91
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  10

制备方法与用途

生物活性

Erlotinib mesylate (CP-358774 mesylate) 为 EGFR 抑制剂，IC50 值为 2 nM。

靶点

EGFR 2 nM (IC 50 )

体外研究

Erlotinib mesylate (CP-358774 mesylate) is also a potent inhibitor of the recombinant intracellular (kinase) domain of the EGFR, with an IC ₅₀ of 1 nM. The proliferation of DiFi cells is strongly inhibited by Erlotinib with an IC ₅₀ of 100 nM for an 8-day proliferation assay. The combination of B-DIM and Erlotinib (2 μM) results in a significant inhibition of colony formation in BxPC-3 cells when compared with either agent alone. The combination of B-DIM and Erlotinib (2 μM) results in a significant induction of apoptosis only in BxPC-3 cells when compare with the apoptotic effect of either agent alone.

体内研究

There is a 1.49-fold statistically significant difference between AUC _0-inf after p.o. administration of Erlotinib (5 mg/kg) comparing Bcrp1/Mdr1a/1b ^-/- and WT mice (7,419±1,720 versus 4,957±1,735 ng*h/mL respectively, P=0.01). The administration of Erlotinib (10 mg/kg/day, or 20 mg/kg/day) to Bleomycin (BLM)-treated rats shows no exacerbation of lung injuries in indices such as macroscopic findings, lung weights, histopathological scores (lung lesion density and lung fibrosis score), and pulmonary hydroxyproline (HyP) level. The result suggests that Erlotinib does not have any exacerbating effects on lung injuries induced by BLM in rats.

反应信息

• 作为产物：
  描述：

  4-(3-氨苯基)-2-甲基-3-丁炔-2-醇 在 sodium hydroxide 作用下， 以 水 、 乙酸乙酯 、 异丙醇 、 甲苯 为溶剂， 反应 23.25h， 生成 甲磺酸厄洛替尼
  参考文献：
  名称：

  Norris, Timothy; Santafianos, Dinos, Journal of the Chemical Society. Perkin Transactions 2 (2001), 2000, # 12, p. 2498 - 2502

  摘要：

  DOI：

文献信息

• Amorphous Erlotinib, processes for the preparation thereof, and processes to prepare additional forms of Erlotinib
  申请人：Gavenda Ales

  公开号：US20090012295A1

  公开（公告）日：2009-01-08

  The present invention provides amorphous erlotinib, processes for the preparation thereof, and processes to prepare additional forms of erlotinib.

  本发明提供非晶态厄洛替尼，其制备方法以及制备额外形式的厄洛替尼的方法。
• [EN] ERLOTINIB SALTS<br/>[FR] SELS D'ERLOTINIB
  申请人：RANBAXY LAB LTD

  公开号：WO2014118737A1

  公开（公告）日：2014-08-07

  The present invention provides erlotinib saccharinate and erlotinib maleate or hydrates thereof, their crystalline forms, processes for their preparation, and pharmaceutical compositions thereof.

  本发明提供厄洛替尼葡萄糖酸盐和厄洛替尼马来酸盐或其水合物，它们的晶体形式，其制备方法以及其药物组合物。
• Combined treatment with an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors
  申请人：Buck A. Elizabeth

  公开号：US20070280928A1

  公开（公告）日：2007-12-06

  The present invention provides a method for treating NSCL, pancreatic, colon or breast cancer tumors or tumor metastases in a patient, comprising administering to the patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein the agent is an mTOR inhibitor, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy. The present invention also provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein said agent is an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. The present invention also provides a pharmaceutical composition comprising an EGFR kinase inhibitor and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing the methods of this invention is the compound erlotinib HCl (also known as TARCEVA®).

  本发明提供了一种治疗患者体内NSCL、胰腺、结肠或乳腺癌肿瘤或肿瘤转移的方法，包括向患者同时或顺序给予治疗有效量的EGFR激酶抑制剂和一种使肿瘤细胞对EGFR激酶抑制剂产生敏感性的药物的组合，其中该药物是mTOR抑制剂，可以附加其他药物或治疗，如其他抗癌药物或放射治疗。本发明还提供了一种治疗患者体内肿瘤或肿瘤转移的方法，包括向患者同时或顺序给予治疗有效量的EGFR激酶抑制剂和一种使肿瘤细胞对EGFR激酶抑制剂产生敏感性的药物的组合，其中该药物是一种能够结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂。本发明还提供了一种制药组合物，包括一种能够结合并直接抑制mTORC1和mTORC2激酶的EGFR激酶抑制剂和mTOR抑制剂，以及一种药用载体。本发明中可用于实施该方法的EGFR激酶抑制剂的首选示例是化合物厄洛替尼盐酸盐（也称为TARCEVA®）。
• [EN] PROCESS FOR THE PREPARATION OF ERLOTINIB OR ITS PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF<br/>[FR] PROCEDE DE PREPARATION D'ERLOTINIB OU DE SES SELS PHARMACEUTIQUEMENT ACCEPTABLES
  申请人：RANBAXY LAB LTD

  公开号：WO2010109443A1

  公开（公告）日：2010-09-30

  The present invention relates to a process for preparation of erlotinib of Formula I or its pharmaceutically acceptable salt thereof. The present invention also relates to process for the preparation of erlotinib trifluoroacetate. The present invention also relates to a noveICrystalline form of erlotinib trifluoroacetate designated as Form E and process for its preparation. The present invention further relates to process for the preparation of erlotinib hydrochloride from erlotinib trifluoroacetate.

  本发明涉及一种制备式I的厄洛替尼或其药学上可接受的盐的方法。本发明还涉及制备厄洛替尼三氟乙酸盐的方法。本发明还涉及一种新的厄洛替尼三氟乙酸盐的晶型，称为E型，以及其制备方法。本发明还涉及从厄洛替尼三氟乙酸盐制备厄洛替尼盐酸盐的方法。
• PROCESS FOR THE PREPARATION OF ERLOTINIB OR ITS PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
  申请人：Murugesan Balaguru

  公开号：US20120101272A1

  公开（公告）日：2012-04-26

  The present invention relates to a process for preparation of erlotinib of Formula I or its pharmaceutically acceptable salt thereof. The present invention also relates to process for the preparation of erlotinib trifluoroacetate. The present invention also relates to a nove-ICrystalline form of erlotinib trifluoroacetate designated as Form E and process for its preparation. The present invention further relates to process for the preparation of erlotinib hydrochloride from erlotinib trifluoroacetate.

  本发明涉及一种制备公式I的厄洛替尼或其药学上可接受的盐的工艺。本发明还涉及一种制备厄洛替尼三氟乙酸盐的工艺。本发明还涉及一种新的厄洛替尼三氟乙酸盐的晶体形式，称为E型，并涉及其制备工艺。本发明还涉及一种从厄洛替尼三氟乙酸盐制备厄洛替尼盐酸盐的工艺。