6-(5-((2-(methylthio)ethylamino)methyl)furan-2-yl)-N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-4-quinazolinamine | 1275595-87-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-(5-((2-(methylthio)ethylamino)methyl)furan-2-yl)-N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-4-quinazolinamine
• 英文别名: N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-6-(5-((2-(methylthio)ethylamino)methyl)-2-furyl)-quinazolin-4-amine；N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-6-(5-((2-(methylthio)ethylamino)methyl)-2-furyl)quinazolin-4-amine；N-(4-(3-fluorobenzyloxy)3-chlorophenyl)-6-(5-((2-(methylthio)ethylamino)methyl)-2-furyl)-quinazolin-4-amine；N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(5-(((2-(methylthio)ethyl)amino)methyl)furan-2-yl)quinazolin-4-amine；N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfanylethylamino)methyl]furan-2-yl]quinazolin-4-amine
• CAS: 1275595-87-3
• 化学式: C₂₉H₂₆ClFN₄O₂S
• 分子量: 549.068
• InChiKey: SVDARJHLGCNCRG-UHFFFAOYSA-N

物化性质

• 沸点：
  677.8±55.0 °C(Predicted)
• 密度：
  1.327±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  97.5
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-(5-((2-(methylthio)ethylamino)methyl)furan-2-yl)-N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-4-quinazolinamine 、 对甲苯磺酸 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成 6-(5-((2-(methylthio)ethylamino)methyl)furan-2-yl)-N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-4-quinazolinamine tosylate
  参考文献：
  名称：

  Discovery of a potent dual EGFR/HER-2 inhibitor L-2 (selatinib) for the treatment of cancer

  摘要：

  To develop potent dual EGFR/HER-2 inhibitors with improved druggability, a series of new lapatinib analogs were designed and synthesized. Compared with lapatinib, L-2, L-4 and M-6 were more active against BT-474 or NCI-N87 cells. In vivo efficacy studies indicated that L-2 significantly suppressed tumor growth in NCI-N87 (94.8% inhibition) or SK-OV-3 xenograft (85.7% inhibition) without causing significant loss of body weight. And the inhibition rates of lapatinib in the two xenograft models were 89.7% and 78.8%, respectively. Moreover, further studies revealed that the potent in vivo activities of L-2 may be mainly attributed to its superior aqueous solubility and oral bioavailability. In addition, a high-yielding one-pot procedure was developed for the synthesis of lapatinib and its analogs. (C) 2013 Elsevier Masson SAS. All tights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.032
• 作为产物：
  描述：

  4-[3-氯-4-(3-氟苄基氧)苯基氨基]-6-碘喹唑啉 在 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 sodium triacetoxyborohydride 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 4.5h， 生成 6-(5-((2-(methylthio)ethylamino)methyl)furan-2-yl)-N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-4-quinazolinamine
  参考文献：
  名称：

  Discovery of a potent dual EGFR/HER-2 inhibitor L-2 (selatinib) for the treatment of cancer

  摘要：

  To develop potent dual EGFR/HER-2 inhibitors with improved druggability, a series of new lapatinib analogs were designed and synthesized. Compared with lapatinib, L-2, L-4 and M-6 were more active against BT-474 or NCI-N87 cells. In vivo efficacy studies indicated that L-2 significantly suppressed tumor growth in NCI-N87 (94.8% inhibition) or SK-OV-3 xenograft (85.7% inhibition) without causing significant loss of body weight. And the inhibition rates of lapatinib in the two xenograft models were 89.7% and 78.8%, respectively. Moreover, further studies revealed that the potent in vivo activities of L-2 may be mainly attributed to its superior aqueous solubility and oral bioavailability. In addition, a high-yielding one-pot procedure was developed for the synthesis of lapatinib and its analogs. (C) 2013 Elsevier Masson SAS. All tights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.032

文献信息

• 4-(Substituted Anilino)-Quinazoline Derivatives Useful as Tyrosine Kinase Inhibitors
  申请人：Wang Jingyi

  公开号：US20120208833A1

  公开（公告）日：2012-08-16

  The present invention relates to 4-(substituted anilino)-quinazoline derivatives as tyrosine kinase inhibitors. Specifically, compounds of formula I, or pharmaceutically acceptable salts or solvates thereof are disclosed, in which each substitutent in formula I is defined in the description. Preparation method of the compounds of formula I, pharmaceutical compositions and pharmaceutical uses thereof are also disclosed. The compounds of formula I are effective tyrosine kinase inhibitors.

  本发明涉及作为酪氨酸激酶抑制剂的4-(取代苯胺基)-喹唑啉衍生物。具体地，公开了式I的化合物，或其药学上可接受的盐或溶剂化合物，其中式I中的每个取代基在描述中有定义。还公开了式I化合物的制备方法，药物组合物以及其药用。式I化合物是有效的酪氨酸激酶抑制剂。
• [EN] HETERO-BIFUNCTIONAL DEGRADER COMPOUNDS AND THEIR USE AS MODULATORS OF TARGETED UBIQUINATION (VHL)<br/>[FR] COMPOSÉS DE DÉGRADATION HÉTÉRO-BIFONCTIONNELS ET LEUR UTILISATION EN TANT QUE MODULATEURS DE L'UBIQUINATION CIBLÉE (VHL)
  申请人：GENENTECH INC

  公开号：WO2019183523A1

  公开（公告）日：2019-09-26

  The present disclosure relates to bifunctional compounds, which can be used as modulators of targeted ubiquitination. In particular, the present disclosure is directed to compounds that contain on one end a VHL ligand moiety, which binds to the VHL ubiquitin ligase (E3), and on the other end a moiety that binds a target protein such that degradation of the target protein/polypeptide is effectuated. The target protein may be EGFR. Also disclosed are VHL ligands.

  本公开涉及双功能化合物，可用作靶向泛素化的调节剂。特别是，本公开是针对包含在一端具有VHL配体基团的化合物，该基团结合到VHL泛素连接酶(E3)，而在另一端具有结合目标蛋白的基团，从而实现目标蛋白/多肽的降解。目标蛋白可以是EGFR。还公开了VHL配体。
• [EN] 4-(SUBSTITUTED ANILINO)QUINAZOLINE DERIVATIVES AS TYROSINE KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE 4-(ANILINO SUBSTITUÉ)QUINAZOLINE À TITRE D'INHIBITEURS DE TYROSINE KINASE
  申请人：QILU PHARMACEUTICAL CO LTD

  公开号：WO2011035540A1

  公开（公告）日：2011-03-31

  4-(substituted anilino)quinazoline derivatives used as inhibitors of tyrosine kinase are disclosed. Specifically, compounds of formula I, pharmaceutically acceptable salts or solvates thereof are disclosed, in which each substitutent of formula I is defined in the description. Preparation method of the compounds of formula I, pharmaceutical compositions and pharmaceutical uses thereof are also disclosed. The compounds of formula I are efficacious inhibitors of tyrosine kinase.

  本文披露了用作酪氨酸激酶抑制剂的4-(取代基苯胺基)喹唑啉衍生物。具体地，披露了公式I的化合物及其药学上可接受的盐或溶剂，其中公式I的每个取代基在描述中有定义。还披露了公式I化合物的制备方法、制药组合物和制药用途。公式I化合物是有效的酪氨酸激酶抑制剂。
• 4-(substituted anilino)-quinazoline derivatives useful as tyrosine kinase inhibitors
  申请人：Wang Jingyi

  公开号：US08916574B2

  公开（公告）日：2014-12-23

  The present invention relates to 4-(substituted anilino)-quinazoline derivatives as tyrosine kinase inhibitors. Specifically, compounds of formula I, or pharmaceutically acceptable salts or solvates thereof are disclosed, in which each substitutent in formula I is defined in the description. Preparation method of the compounds of formula I, pharmaceutical compositions and pharmaceutical uses thereof are also disclosed. The compounds of formula I are effective tyrosine kinase inhibitors.

  本发明涉及4-(取代苯胺基)-喹唑啉衍生物作为酪氨酸激酶抑制剂。具体地，公开了公式I的化合物或其药学上可接受的盐或溶剂，其中公式I中的每个取代基在描述中有定义。还公开了公式I的化合物的制备方法，以及其药物组合物和药物用途。公式I的化合物是有效的酪氨酸激酶抑制剂。
• 4-(SUBSTITUTED ANILINO)QUINAZOLINE DERIVATIVES AS TYROSINE KINASE INHIBITORS
  申请人：Qilu Pharmaceutical Co., Ltd

  公开号：EP2484678B1

  公开（公告）日：2015-01-21