2-[4-[4-(三氟甲基)苯甲酰胺基]]]苯甲基4,6-二(二甲氨基)-嘧啶-5-乙酸 | 1093108-50-9

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-[4-[4-(三氟甲基)苯甲酰胺基]]]苯甲基4,6-二(二甲氨基)-嘧啶-5-乙酸
• 英文名称: BI-671800
• 英文别名: actimis；{4,6-bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)-benzyl)pyrimidin-5-yl} acetic acid；[4,6-bis(dimethylamino)-2-(4-{[4-(trifluoromethyl)benzoyl]amino}benzyl)pyrimidin-5-yl] acetic acid；5-Pyrimidineacetic acid, 4,6-bis(dimethylamino)-2-((4-((4-(trifluoromethyl)benzoyl)amino)phenyl)methyl)-；2-[4,6-bis(dimethylamino)-2-[[4-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid
• CAS: 1093108-50-9
• 化学式: C₂₅H₂₆F₃N₅O₃
• 分子量: 501.508
• InChiKey: XEOSTBFUCNZKGS-UHFFFAOYSA-N

物化性质

• 沸点：
  611.4±55.0 °C(Predicted)
• 密度：
  1.351±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  10

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性

BI-671800（AP-761，Cmpd A）是一种高度特异性的chemoattractant receptor-homologous molecule on Tb cells (DP2/CRTH2) 拮抗剂。其对人类和鼠类CRTH2的结合IC50值分别为4.5 nM和3.7 nM。BI-671800 与无症状初治哮喘患者及ICS患者的FEV1略有改善有关。

靶点

Target	Value
murine CRTH2 (Cell-free assay)	3.7 nM
human CRTH2 (Cell-free assay)	4.5 nM

反应信息

• 作为反应物：
  描述：

  2-[4-[4-(三氟甲基)苯甲酰胺基]]]苯甲基4,6-二(二甲氨基)-嘧啶-5-乙酸 在 氨 作用下， 生成
  参考文献：
  名称：

  WO2008/156781

  摘要：

  公开号：
• 作为产物：
  描述：

  2-[4-[4-(三氟甲基)苯甲酰胺基]]]苯甲基4,6-二(二甲氨基)-嘧啶-5-乙酸甲酯 在 lithium hydroxide monohydrate 、 水 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.5h， 以90%的产率得到2-[4-[4-(三氟甲基)苯甲酰胺基]]]苯甲基4,6-二(二甲氨基)-嘧啶-5-乙酸
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARING [4,6-BIS-DIMETHYLAMINO-2-[4-(4-TRIFLUOROMETHYLBENZOYL-AMINO)BENZYL]PYRIMIDIN-5-YL]ACETIC ACID
  [FR] PROCÉDÉ DE PRÉPARATION DE L'ACIDE [4,6-BIS-DIMÉTHYLAMINO-2-[4-(4-TRIFLUOROMÉTHYLBENZOYL-AMINO)BENZYL]PYRIMIDIN-5-YL] ACÉTIQUE

  摘要：

  本发明涉及一种制备化合物（I）的方法。

  公开号：

  WO2012156221A1

文献信息

• ISOTOPICALLY ENRICHED PYRIMIDIN-5-YL ACETIC ACID DERIVATIVES AS CRTH2 ANTAGONISTS
  申请人：Ly Tai Wei

  公开号：US20110172250A1

  公开（公告）日：2011-07-14

  Provided herein are 2 H- and 13 C-enriched compounds of formula (I) or (II); wherein R is as defined herein, and wherein at least one hydrogen atom, in certain embodiments, three or more hydrogen atoms, are deuterium atoms or at least one carbon atom is a carbon-13 atom. Also provided are pharmaceutical compositions and methods using the 2 H- and 13 C-enriched compounds, useful for treating CRTH2-related diseases or disorders such as, for example, asthma, allergic rhinitis, atopic dermatitis, allergic conjuvatitis, Churg-Strauss syndrome, sinusitis, basophilic leukemia, chronic urticaria or basophilic leukocytosis.

  本文提供了公式（I）或（II）的2H-和13C富集化合物；其中R如本文所定义，并且在某些情况下，至少一个氢原子，甚至三个或更多个氢原子，是氘原子，或者至少一个碳原子是碳-13原子。还提供了使用这些2H-和13C富集化合物的药物组合物和方法，用于治疗CRTH2相关疾病或疾病，例如哮喘、过敏性鼻炎、特应性皮炎、过敏性结膜炎、Churg-Strauss综合症、鼻窦炎、嗜碱性白血病、慢性荨麻疹或嗜碱性白细胞增多症。
• [EN] PROCESS FOR PREPARING A POLYMORPH OF THE CHOLINE SALT OF A PYRIMIDIN-5-YL ACETIC ACID DERIVATIVE<br/>[FR] PROCEDE DE PREPARATION D'UN POLYMORPHE DE SEL DE CHOLINE DE DERIVE D'ACIDE PYRIMIDIN-5-YL ACETIQUE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2011066176A1

  公开（公告）日：2011-06-03

  Provided is a process for preparing a choline salt of [4,6-bis(dimethylamino)-2-(4- [4- (trifluoromethyl)benzoyl] amino }benzyl)pyrimidin-5-yl] acetic acid. The process of the invention is useful for preparing the salt in purer forms of the salt. Also disclosed is a more pure form of the of choline salt of [4,6-bis(dimethylamino)-2-(4- [4- (trifluoromethyl)benzoyl] amino }benzyl)pyrimidin-5-yl] acetic acid.

  提供了一种制备[4,6-双(二甲基氨基)-2-(4-[4-(三氟甲基)苯甲酰]氨基}苯基)嘧啶-5-基]乙酸胆碱盐的过程。该发明的方法可用于制备更纯的盐形式。还公开了[4,6-双(二甲基氨基)-2-(4-[4-(三氟甲基)苯甲酰]氨基}苯基)嘧啶-5-基]乙酸胆碱盐的更纯净形式。
• Pyrimidine derivatives useful for the treatment of diseases mediated by crth2
  申请人：Ly Tai-wei

  公开号：US20070129355A1

  公开（公告）日：2007-06-07

  The present invention relates to a pyrimidine derivative of the formula (I) and salts thereof which is useful as an active ingredient of pharmaceutical preparations. The pyrimidine derivative of the present invention has excellent CRTH2 (G-protein-coupled chemoattractant receptor, expressed on Th2 cells) antagonistic activity and can be used for the prophylaxis and treatment of diseases associated with CRTH2 activity, in particular for the treatment of allergic diseases, such as asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis; eosinophil-related diseases, such as Churg-Strauss syndrome and sinusitis; basophil-related diseases, such as basophilic leukemia, chronic urticaria and basophilic leukocytosis in human and other mammals; and inflammatory diseases characterized by T lymphocytes and profuse leukocyte infiltrates such as psoriasis, eczema, inflammatory bowel disease, ulcerative colitis, Crohn's disease, COPD (chronic obstructive pulmonary disorder) and arthritis.

  本发明涉及一种嘧啶衍生物（I）及其盐，可用作制药制剂的有效成分。本发明的嘧啶衍生物具有优异的CRTH2（G蛋白偶联化合物趋化因子受体，表达于Th2细胞上）拮抗活性，可用于预防和治疗与CRTH2活性相关的疾病，特别是用于治疗过敏性疾病，如哮喘、过敏性鼻炎、特应性皮炎和过敏性结膜炎；嗜酸性粒细胞相关疾病，如Churg-Strauss综合征和鼻窦炎；嗜碱性粒细胞相关疾病，如嗜碱性白血病、慢性荨麻疹和人类及其他哺乳动物的嗜碱性白细胞增多症；以及以T淋巴细胞和大量白细胞浸润为特征的炎性疾病，如牛皮癣、湿疹、炎症性肠病、溃疡性结肠炎、COPD（慢性阻塞性肺疾病）和关节炎。
• Pyrimidine derivatives useful for the treatment of diseases mediated by CRTH2
  申请人：Actimis Pharmaceuticals, Inc.

  公开号：US07960393B2

  公开（公告）日：2011-06-14

  The present invention relates to a pyrimidine derivative of the formula (I) and salts thereof which is useful as an active ingredient of pharmaceutical preparations. The pyrimidine derivative of the present invention has excellent CRTH2 (G-protein-coupled chemoattractant receptor, expressed on Th2 cells) antagonistic activity and can be used for the prophylaxis and treatment of diseases associated with CRTH2 activity, in particular for the treatment of allergic diseases, such as asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis; eosinophil-related diseases, such as Churg-Strauss syndrome and sinusitis; basophil-related diseases, such as basophilic leukemia, chronic urticaria and basophilic leukocytosis in human and other mammals; and inflammatory diseases characterized by T lymphocytes and profuse leukocyte infiltrates such as psoriasis, eczema, inflammatory bowel disease, ulcerative colitis, Crohn's disease, COPD (chronic obstructive pulmonary disorder) and arthritis.

  本发明涉及一种式（I）的嘧啶衍生物及其盐，可用作制药制剂的活性成分。本发明的嘧啶衍生物具有优异的CRTH2（表达于Th2细胞上的G蛋白偶联趋化因子受体）拮抗活性，可用于预防和治疗与CRTH2活性相关的疾病，特别是用于治疗过敏性疾病，如哮喘、过敏性鼻炎、特应性皮炎和过敏性结膜炎；嗜酸性粒细胞相关疾病，如Churg-Strauss综合征和鼻窦炎；嗜碱性粒细胞相关疾病，如嗜碱性白血病、慢性荨麻疹和哺乳动物中的嗜碱性白细胞增多症；以及以T淋巴细胞和丰富的白细胞浸润为特征的炎症性疾病，如牛皮癣、湿疹、炎症性肠病、溃疡性结肠炎、COPD（慢性阻塞性肺疾病）和关节炎。
• Process for preparing [4,6-bis-dimethylamino-2-[4-(4-trifluoromethylbenzoylamino)benzyl]pyrimidin-5-yl]acetic acid
  申请人：Rodriguez Dehli Juan M.

  公开号：US08859770B2

  公开（公告）日：2014-10-14

  The present invention relates to a process for preparing a compound of formula (I).

  本发明涉及一种制备式(I)化合物的过程。