N-(2-(4-chloro-7-methoxy-1'-neopentylspiro[indoline-3,4'-piperidin]-1-yl)phenyl)-4-phenylthiazol-2-amine | 1609548-29-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(2-(4-chloro-7-methoxy-1'-neopentylspiro[indoline-3,4'-piperidin]-1-yl)phenyl)-4-phenylthiazol-2-amine
• CAS: 1609548-29-9
• 化学式: C₃₃H₃₇ClN₄OS
• 分子量: 573.202
• InChiKey: CQEMKODDEIRSPQ-UHFFFAOYSA-N

物化性质

• 沸点：
  711.4±70.0 °C(predicted)
• 密度：
  1.28±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.75
• 重原子数：
  40.0
• 可旋转键数：
  6.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  40.63
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-(2-(4-chloro-7-methoxy-1'-neopentylspiro[indoline-3,4'-piperidin]-1-yl)phenyl)-4-phenylthiazol-2-amine 在 三氯化硼 、 四丁基碘化铵 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以39%的产率得到4-chloro-1'-(2,2-dimethylpropyl)-1-[2-[(4-phenyl-1,3-thiazol-2-yl)amino]phenyl]spiro[2H-indole-3,4'-piperidine]-7-ol
  参考文献：
  名称：

  2-Amino-1,3,4-thiadiazoles in the 7-hydroxy-N-neopentyl spiropiperidine indolinyl series as potent P2Y1 receptor antagonists

  摘要：

  Blockade of the P2Y(1) receptor is important to the treatment of thrombosis with potentially improved safety margins compared with P2Y(12) receptor antagonists. Investigation of a series of urea surrogates of the diaryl urea lead 3 led to the discovery of 2-amino-1,3,4-thiadiazoles in the 7-hydroxy-N-neopentyl spiropiperidine indolinyl series as potent P2Y(1) receptor antagonists, among which compound 5a was the most potent and the first non-urea analog with platelet aggregation (PA) IC50 less than 0.5 mu M with 10 mu M ADP. Several 2-amino-1,3,4-thiadiazole analogs such as 5b and 5f had a more favorable pharmacokinetic profile, such as higher C-trough, lower Cl, smaller V-dss, and similar bioavailability compared with 3. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.011
• 作为产物：
  描述：

  4-chloro-7-methoxy-1'-neopentylspiro[indoline-3,4'-piperidine] 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 为溶剂， 反应 32.0h， 生成 N-(2-(4-chloro-7-methoxy-1'-neopentylspiro[indoline-3,4'-piperidin]-1-yl)phenyl)-4-phenylthiazol-2-amine
  参考文献：
  名称：

  2-Amino-1,3,4-thiadiazoles in the 7-hydroxy-N-neopentyl spiropiperidine indolinyl series as potent P2Y1 receptor antagonists

  摘要：

  Blockade of the P2Y(1) receptor is important to the treatment of thrombosis with potentially improved safety margins compared with P2Y(12) receptor antagonists. Investigation of a series of urea surrogates of the diaryl urea lead 3 led to the discovery of 2-amino-1,3,4-thiadiazoles in the 7-hydroxy-N-neopentyl spiropiperidine indolinyl series as potent P2Y(1) receptor antagonists, among which compound 5a was the most potent and the first non-urea analog with platelet aggregation (PA) IC50 less than 0.5 mu M with 10 mu M ADP. Several 2-amino-1,3,4-thiadiazole analogs such as 5b and 5f had a more favorable pharmacokinetic profile, such as higher C-trough, lower Cl, smaller V-dss, and similar bioavailability compared with 3. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.011