4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide | 1190836-34-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide
• 英文别名: 4-[2-fluoro-4-[[(2-phenylacetylamino)thioxomethyl]amino]phenoxy]-7-methoxy-N-methyl-6-quinolinecarboxamide；Pamufetinib；4-[2-fluoro-4-[(2-phenylacetyl)carbamothioylamino]phenoxy]-7-methoxy-N-methylquinoline-6-carboxamide
• CAS: 1190836-34-0
• 化学式: C₂₇H₂₃FN₄O₄S
• 分子量: 518.568
• InChiKey: ORRNXRYWGDUDOG-UHFFFAOYSA-N

物化性质

• 密度：
  1.364±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO:10.0(最大浓度 mg/mL);19.28(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  134
• 氢给体数：
  3
• 氢受体数：
  7

安全信息

• 储存条件：
  2-8℃

制备方法与用途

TAS-115 是一种有效抑制剂，能分别以30和32纳摩尔的浓度抑制rVEGFR2和rMET的活性。

反应信息

• 作为反应物：
  描述：

  4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide 在 盐酸 作用下， 以 水 为溶剂， 生成
  参考文献：
  名称：

  MESYLIC ACID SALT OF ACYLTHIOUREA COMPOUND, CRYSTAL OF THE SAME, AND PROCESS FOR PRODUCING THESE

  摘要：

  本发明的一个目的是提供一种盐类化合物，其化学式为4-(2-氟-4-(3-(2-苯乙酰基)硫脲基)苯氧基)-7-甲氧基-N-甲基喹啉-6-甲酰胺，该化合物可用作抗肿瘤药物，并且提供该盐类化合物的晶体。该盐类化合物和晶体在溶解性、稳定性和口服吸收性方面表现出色，并且可以进行批量生产。本发明涉及：4-(2-氟-4-(3-(2-苯乙酰基)硫脲基)苯氧基)-7-甲氧基-N-甲基喹啉-6-甲酰胺的甲磺酸盐；以及包括具有特定衍射角度的特征峰的X射线粉末衍射谱的甲磺酸盐晶体。

  公开号：

  US20180161317A1
• 作为产物：
  描述：

  4-[2-Fluoro-4-[(2-phenylacetyl)carbamothioylamino]phenoxy]-7-methoxyquinoline-6-carboxylic acid 以96的产率得到4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide
  参考文献：
  名称：

  Acylthiourea compound or salt thereof, and use thereof

  摘要：

  提供的是一种c-Met抑制剂的抗肿瘤药物，通过选择性地影响c-Met特异表达的肿瘤细胞来缓解副作用，其化学式为（I）或其盐： 其中，R1和R2各自独立地为氢原子、可选取代的C1-6烷基、C3-10环烷基、C6-14芳香烃或饱和或不饱和的杂环基，或R1和R2可以与它们连接的氮原子一起形成可选取代的含氮杂环环；R3为C1-6烷基；R4、R5和R6各自独立地为氢原子、卤素原子、可选取代的C1-6烷基、C1-6烷氧基、C1-6烷基氨基、可选取代的芳香烃基或可选取代的饱和或不饱和的杂环基，或R5和R6可以与它们连接的苯环一起形成环。

  公开号：

  US08304427B2

文献信息

• ACYLTHIOUREA COMPOUND OR SALT THEREOF, AND USE THEREOF
  申请人：Suda Yoshimitsu

  公开号：US20110034439A1

  公开（公告）日：2011-02-10

  To provide an antitumor agent which exhibits excellent c-Met inhibitory effect and mitigates side effects by virtue of selectively affecting to tumor cells in which c-Met is specifically expressed. The invention provides an acylthiourea compound represented by formula (I): (wherein each of R 1 and R 2 , which may be the same or different, represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 3-10 cycloalkyl group, an optionally substituted C 6-14 aromatic hydrocarbon group, or an optionally substituted saturated or unsaturated heterocyclic group, or R 1 and R 2 may form, together with the nitrogen atom to which they are attached, an optionally substituted nitrogen-containing heterocyclic ring; R 3 represents a C 1-6 alkyl group; and each of R 4 , R 5 , and R 6 , which may be identical to or different from one another, represents a hydrogen atom, a halogen atom, an optionally substituted C 1-6 alkyl group, a C 1-6 alkoxy group, a C 1-6 alkylamino group, an optionally substituted aromatic hydrocarbon group, or an optionally substituted saturated or unsaturated heterocyclic group, or R 5 and R 6 may form a ring together with the phenyl ring to which they are attached) or a salt thereof.

  提供一种抗肿瘤剂，其表现出优异的c-Met抑制作用，并通过选择性地影响c-Met特异表达的肿瘤细胞来减轻副作用。本发明提供一种由式(I)表示的酰基硫脲化合物：（其中，R1和R2中的每一个，可以相同也可以不同，表示氢原子，可选取代的C1-6烷基，可选取代的C3-10环烷基，可选取代的C6-14芳香烃基，或可选取代的饱和或不饱和杂环基，或R1和R2可以与它们所附着的氮原子一起形成一个可选取代的含氮杂环环；R3表示C1-6烷基；R4、R5和R6中的每一个，可以相同也可以不同，表示氢原子，卤素原子，可选取代的C1-6烷基，C1-6烷氧基，C1-6烷基氨基，可选取代的芳香烃基，或可选取代的饱和或不饱和杂环基，或R5和R6可以与它们所附着的苯环一起形成一个环）。或其盐。
• ACYLTHIOUREA COMPOUND OR SALT THEREOF, AND USE OF THE COMPOUND OR THE SALT
  申请人：Taiho Pharmaceutical Co., Ltd.

  公开号：EP2287155A1

  公开（公告）日：2011-02-23

  To provide an antitumor agent which exhibits excellent c-Met inhibitory effect and mitigates side effects by virtue of selectively affecting to tumor cells in which c-Met is specifically expressed. The invention provides an acylthiourea compound represented by formula (I): (wherein each of R1 and R2, which may be the same or different, represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C6-14 aromatic hydrocarbon group, or an optionally substituted saturated or unsaturated heterocyclic group, or R1 and R2 may form, together with the nitrogen atom to which they are attached, an optionally substituted nitrogen-containing heterocyclic ring; R3 represents a C1-6 alkyl group; and each of R4, R5, and R6, which may be identical to or different from one another, represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, a C1-6 alkoxy group, a C1-6 alkylamino group, an optionally substituted aromatic hydrocarbon group, or an optionally substituted saturated or unsaturated heterocyclic group, or R5 and R6 may form a ring together with the phenyl ring to which they are attached) or a salt thereof.

  提供一种抗肿瘤药，该抗肿瘤药对特异性表达 c-Met 的肿瘤细胞具有选择性影响，从而显示出卓越的 c-Met 抑制作用并减轻副作用。 本发明提供了一种由式（I）代表的酰基硫脲化合物： (其中 R1 和 R2（可以相同或不同）各自代表氢原子、任选取代的 C1-6 烷基、任选取代的 C3-10 环烷基、任选取代的 C6-14 芳烃基团或任选取代的饱和或不饱和杂环基团，或 R1 和 R2 可与所连接的氮原子一起形成任选取代的含氮杂环；R3代表C1-6烷基；R4、R5和R6（它们可以彼此相同或不同）分别代表氢原子、卤素原子、任选取代的C1-6烷基、C1-6烷氧基、C1-6烷氨基、任选取代的芳香烃基团或任选取代的饱和或不饱和杂环基团，或R5和R6可与它们所连接的苯基环一起形成环）或其盐。
• EFFECT POTENTIATOR FOR ANTITUMOR AGENTS
  申请人：Taiho Pharmaceutical Co., Ltd.

  公开号：EP2799070A1

  公开（公告）日：2014-11-05

  An antitumor effect potentiator of another antitumor agent, including an acylthiourea compound represented by formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient: wherein R1 represents a C1-6 alkyl group which may have a substituent, while the substituent represents any one of a hydroxyl group, a C3-10 cycloalkyl group, a C1-6 alkoxy group which may have a substituent, a C1-6 alkylamino group which may have a substituent, a C1-6 alkanoylamino group, a C1-6 alkylsulfonyl group, a C6-14 aromatic hydrocarbon group which may have a substituent, a saturated or unsaturated heterocyclic group which may have a substituent, a C1-6 alkylaminocarbonyl group which may have a substituent, a saturated or unsaturated heterocyclic carbonyl group which may have a substituent; R2 represents a fluorine atom or a chlorine atom; and R3 represents a hydrogen atom, a fluorine atom, or a chlorine atom.

  另一种抗肿瘤药的抗肿瘤作用增效剂，包括作为活性成分的由式（I）代表的酰基硫脲化合物或其药学上可接受的盐： 其中 R1 代表可能具有取代基的 C1-6 烷基，而取代基代表羟基、C3-10 环烷基、可能具有取代基的 C1-6 烷氧基、可能具有取代基的 C1-6 烷氨基、C1-6 烷酰胺基中的任意一种、C1-6烷基磺酰基、可带有取代基的C6-14芳香烃基、可带有取代基的饱和或不饱和杂环基、可带有取代基的C1-6烷基氨基羰基、可带有取代基的饱和或不饱和杂环羰基；R2 代表氟原子或氯原子；以及 R3 代表氢原子、氟原子或氯原子。
• THERAPEUTIC AGENT FOR OSTEOPOROSIS
  申请人：National University Corporation Tokyo University Of Agriculture and Technology

  公开号：EP3053581A1

  公开（公告）日：2016-08-10

  To provide an agent for treating osteoporosis, comprising an acyl thiourea compound represented by the following formula (I), wherein R1 represents an optionally substituted C1-6 alkyl group; R2 represents a fluorine atom or a chlorine atom; and R3 represents a hydrogen atom, a fluorine atom, or a chlorine atom, or a salt thereof as an active ingredient.

  提供一种治疗骨质疏松症的制剂，其活性成分包括由下式（I）代表的酰基硫脲化合物，其中 R1 代表任选取代的 C1-6 烷基；R2 代表氟原子或氯原子；R3 代表氢原子、氟原子或氯原子或其盐。
• MESYLIC ACID SALT OF ACYLTHIOUREA COMPOUND, CRYSTAL THEREOF, AND PRODUCTION PROCESSES THEREFOR
  申请人：Taiho Pharmaceutical Co., Ltd.

  公开号：EP3290405A1

  公开（公告）日：2018-03-07

  The purpose of the present invention is to provide a salt of 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide, which is useful as an antitumor drug, and crystals of the salt, the salt and crystals being excellent in terms of solubility, stability, and oral absorbability and being capable of mass-production. The present invention relates to a mesylic acid salt of 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide and to the mesylic acid salt including crystals which give an X-ray powder diffraction spectrum having characteristic peaks at given diffraction angles.

  本发明的目的是提供一种可作为抗肿瘤药物的4-(2-氟-4-(3-(2-苯乙酰基)硫脲基)苯氧基)-7-甲氧基-N-甲基喹啉-6-甲酰胺的盐和该盐的晶体，该盐和晶体在溶解性、稳定性和口服吸收性方面性能优良，并能大量生产。本发明涉及 4-(2-氟-4-(3-(2-苯乙酰基)硫脲基)苯氧基)-7-甲氧基-N-甲基喹啉-6-甲酰胺的甲磺酸盐，以及包括晶体在内的甲磺酸盐，该晶体的 X 射线粉末衍射谱在给定的衍射角上具有特征峰。