(S)-2-((6-(4-(hydroxymethyl)phenyl)thieno[2,3-d]pyrimidin-4-yl)amino)-2-phenylethan-1-ol | 1580542-41-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: (S)-2-((6-(4-(hydroxymethyl)phenyl)thieno[2,3-d]pyrimidin-4-yl)amino)-2-phenylethan-1-ol
• 英文别名: (2S)-2-[[6-[4-(hydroxymethyl)phenyl]thieno[2,3-d]pyrimidin-4-yl]amino]-2-phenylethanol
• CAS: 1580542-41-1
• 化学式: C₂₁H₁₉N₃O₂S
• 分子量: 377.467
• InChiKey: IOOGDMGZEOPPPA-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(hydroxymethyl)phenylboronic acid MIDA ester 、 (S)-2-((6-bromothieno[2,3-d]pyrimidin-4-yl)amino)-2-phenylethanol hydrochloride 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 4.0h， 以84%的产率得到(S)-2-((6-(4-(hydroxymethyl)phenyl)thieno[2,3-d]pyrimidin-4-yl)amino)-2-phenylethan-1-ol
  参考文献：
  名称：

  Structure–activity study leading to identification of a highly active thienopyrimidine based EGFR inhibitor

  摘要：

  Based on the thieno[2,3-d]pyrimidine scaffold, a series of new 4-amino-6-aryl thienopyrimidines have been prepared and evaluated as EGFR tyrosine kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 6-aryl ring, the stereochemistry, and the basicity at the secondary 4-amino group. A stepwise optimization by combination of active fragments led to the discovery of three structures with EGFR IC50 < 1 nM. The most potent drug candidate had an IC50 of 0.3 nM towards EGFR and its mutants L858R and L861Q. Studies using human cancer cell lines and an EGFR-L858R reporter cell system revealed good cellular potency, verifying the identified thienopyrimidines as promising lead structures. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.042

文献信息

• [EN] 4-AMINO-6-ARYL[2,3-D]PYRIMIDINES FOR THE INHIBITION OF EGFR TYROSINE KINASE<br/>[FR] 4-AMINO-6-ARYL[2,3-D]PYRIMIDINES POUR L'INHIBITION DE LA TYROSINE KINASE AU NIVEAU DE L'EGFR
  申请人：NORWEGIAN UNIV SCI & TECH NTNU

  公开号：WO2015000959A1

  公开（公告）日：2015-01-08

  This invention relates to certain new pyrrolo-, thieno-, and furo-[2,3- d]pyrimidine compounds, such as of general formula (I) These compounds are epidermal growth factor receptor tyrosine kinase inhibitors and therefore offer potential in the treatment of cancer.

  这项发明涉及某些新的吡咯基、噻吩基和呋喃基[2,3-d]嘧啶化合物，如一般式(I)所示。这些化合物是表皮生长因子受体酪氨酸激酶抑制剂，因此在癌症治疗中具有潜力。