tert-butyl 4-[(1S)-1-benzyl-2-hydroxyethyl]amino-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-7-carboxylate | 1252686-68-2

• 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: tert-butyl 4-[(1S)-1-benzyl-2-hydroxyethyl]amino-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-7-carboxylate
• 英文别名: tert-butyl 3-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6-tetraene-11-carboxylate
• CAS: 1252686-68-2
• 化学式: C₂₃H₂₈N₄O₃S
• 分子量: 440.566
• InChiKey: GRCOHMFIXXHSEK-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(1S)-1-benzyl-2-hydroxyethyl]amino-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-7-carboxylate 在 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 以96%的产率得到(2S)-3-phenyl-2-(5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-ylamino)propan-1-ol
  参考文献：
  名称：

  Design and Synthesis of Tetrahydropyridothieno[2,3-d]pyrimidine Scaffold Based Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors: The Role of Side Chain Chirality and Michael Acceptor Group for Maximal Potency

  摘要：

  HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model.

  DOI：

  10.1021/jm100607r
• 作为产物：
  描述：

  4-氯-5,6-二氢吡啶并[4',3'4,5]噻吩并[2,3-D]嘧啶-7(8H)-甲酸叔丁基酯 、 L-苯丙氨醇 以 乙醇 为溶剂， 反应 8.0h， 以87%的产率得到tert-butyl 4-[(1S)-1-benzyl-2-hydroxyethyl]amino-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-7-carboxylate
  参考文献：
  名称：

  Design and Synthesis of Tetrahydropyridothieno[2,3-d]pyrimidine Scaffold Based Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors: The Role of Side Chain Chirality and Michael Acceptor Group for Maximal Potency

  摘要：

  HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model.

  DOI：

  10.1021/jm100607r

文献信息

• Design and Synthesis of Tetrahydropyridothieno[2,3-<i>d</i>]pyrimidine Scaffold Based Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors: The Role of Side Chain Chirality and Michael Acceptor Group for Maximal Potency
  作者：Chia-Hsien Wu、Mohane Selvaraj Coumar、Chang-Ying Chu、Wen-Hsing Lin、Yi-Rong Chen、Chiung-Tong Chen、Hui-Yi Shiao、Shaik Rafi、Sing-Yi Wang、Hui Hsu、Chun-Hwa Chen、Chun-Yu Chang、Teng-Yuan Chang、Tzu-Wen Lien、Ming-Yu Fang、Kai-Chia Yeh、Ching-Ping Chen、Teng-Kuang Yeh、Su-Huei Hsieh、John T.-A. Hsu、Chun-Chen Liao、Yu-Sheng Chao、Hsing-Pang Hsieh

  DOI：10.1021/jm100607r

  日期：2010.10.28

  HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model.