6-(2,4-difluorophenoxy)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one | 1280218-22-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(2,4-difluorophenoxy)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one
• 英文别名: 6-(2,4-difluorophenoxy)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one
• CAS: 1280218-22-5
• 化学式: C₁₄H₉F₂N₃O₂S
• 分子量: 321.307
• InChiKey: SNISZNOMJZVSPR-UHFFFAOYSA-N

物化性质

• 熔点：
  265.5-266.7 °C
• 沸点：
  440.1±55.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  89.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-(2,4-difluorophenoxy)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one 在 三丁基膦 、 间氯过氧苯甲酸 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-(2,4-difluorophenoxy)-2-methanesulfonyl-8-(2-methanesulfonylethyl)-8H-pyrido[2,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Discovery of 6-(2,4-Difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (Pamapimod) and 6-(2,4-Difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as Orally Bioavailable and Highly Selective Inhibitors of p38α Mitogen-Activated Protein Kinase

  摘要：

  The development of a new series of p38 alpha inhibitors resulted in the identification of two clinical candidates, one of which was advanced into a phase 2 clinical study for rheumatoid arthritis. The original lead, an lck inhibitor that also potently inhibited p38a, was a screening hit from our kinase inhibitor library. This manuscript describes the optimization of the lead to p38-selective examples with good pharmacokinetic properties.

  DOI：

  10.1021/jm101423y
• 作为产物：
  描述：

  6-氨基-2-硫代-1,2-二氢-5-嘧啶甲醛 在 potassium carbonate 作用下， 以 N-甲基吡咯烷酮 、 丙酮 为溶剂， 生成 6-(2,4-difluorophenoxy)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one
  参考文献：
  名称：

  Discovery of 6-(2,4-Difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (Pamapimod) and 6-(2,4-Difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as Orally Bioavailable and Highly Selective Inhibitors of p38α Mitogen-Activated Protein Kinase

  摘要：

  The development of a new series of p38 alpha inhibitors resulted in the identification of two clinical candidates, one of which was advanced into a phase 2 clinical study for rheumatoid arthritis. The original lead, an lck inhibitor that also potently inhibited p38a, was a screening hit from our kinase inhibitor library. This manuscript describes the optimization of the lead to p38-selective examples with good pharmacokinetic properties.

  DOI：

  10.1021/jm101423y

文献信息

• 含并环类衍生物抑制剂、其制备方法和应用
  申请人：上海翰森生物医药科技有限公司

  公开号：CN112079830A

  公开（公告）日：2020-12-15

  本发明涉及含并环类衍生物抑制剂、其制备方法和应用。特别地，本发明涉及通式(I)所示的化合物、其制备方法及含有该化合物的药物组合物，及其作为激酶抑制剂，尤其是作为受体酪氨酸激酶抑制剂(TKI)，更具体地，作为EGFR或HER2抑制剂在治疗癌症、炎症、慢性肝病、糖尿病、心血管疾病和AIDS等相关疾病的用途，其中通式(I)中的各取代基与说明书中的定义相同。
• [EN] INHIBITORS OF EGFR AND/OR HER2 AND METHODS OF USE<br/>[FR] INHIBITEURS D'EGFR ET/OU DE HER2 ET PROCÉDÉS D'UTILISATION
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2019046775A1

  公开（公告）日：2019-03-07

  The application relates to a compound having Formula X: which modulates the activity of HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, plays a role.

  该申请涉及一种具有公式X的化合物：该化合物调节HER2和/或其突变体以及/或EGFR和/或其突变体的活性，一种包含该化合物的药物组合物，以及一种治疗或预防HER2和/或其突变体以及/或EGFR和/或其突变体发挥作用的疾病的方法。
• Hydroxyalkyl substituted pyrido-7-pyrimidin-7-ones
  申请人：Goldstein Michael David

  公开号：US20080119497A1

  公开（公告）日：2008-05-22

  Compounds of the Formula: where X 1 , Ar 1 , R 1 , and R 2 are as defined herein, and compositions comprising the same. Also provided are methods for using compounds of Formula I in treating p38 mediated disorders in a patient.

  本发明提供了以下公式的化合物：其中X1，Ar1，R1和R2如定义所述，并且包括这些化合物的组合物。还提供了使用公式I的化合物治疗患者的p38介导的疾病的方法。
• Inhibitors of EGFR and/or HER2 and methods of use
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US11186574B2

  公开（公告）日：2021-11-30

  The application relates to a compound having Formula X: which modulates the activity of HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, plays a role.

  本申请涉及一种具有式 X 的化合物：该化合物可调节 HER2 和/或其突变体和/或表皮生长因子受体和/或其突变体的活性；一种包含该化合物的药物组合物；以及一种治疗或预防 HER2 和/或其突变体和/或表皮生长因子受体和/或其突变体在其中起作用的疾病的方法。
• INHIBITORS OF EGFR AND/OR HER2 AND METHODS OF USE
  申请人：HATCHER John M.

  公开号：US20200199121A1

  公开（公告）日：2020-06-25

  The application relates to a compound having Formula X: which modulates the activity of HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, plays a role.