1-(2-(5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-ylamino)phenyl)-1'-neopentyl-4-(trifluoromethyl)spiro[indoline-3,4'-piperidin]-7-ol | 1554014-53-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(2-(5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-ylamino)phenyl)-1'-neopentyl-4-(trifluoromethyl)spiro[indoline-3,4'-piperidin]-7-ol
• 英文别名: 1-[2-[[5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-yl]amino]phenyl]-1'-(2,2-dimethylpropyl)-4-(trifluoromethyl)spiro[2H-indole-3,4'-piperidine]-7-ol
• CAS: 1554014-53-7
• 化学式: C₃₆H₄₂F₃N₅OS
• 分子量: 649.824
• InChiKey: BHFWFSACFRIJPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.9
• 重原子数：
  46
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  92.8
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-(2-(5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-ylamino)phenyl)-1'-neopentyl-4-(trifluoromethyl)spiro[indoline-3,4'-piperidin]-7-ol 在 ammonium hydroxide 、 sodium hydroxide 作用下， 反应 72.0h， 以76%的产率得到1-(2-{[5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-yl]amino}phenyl)-1'-neopentyl-7-hydroxy-1,2-dihydrospiro[indole-3,4'-piperidine]-4-carbonitrile
  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：

  5-(4-(tert-butyl)phenyl)-N-(2-(7-methoxy-1'-neopentyl-4-(trifluoromethyl)spiro[indoline-3,4'-piperidin]-1-yl)phenyl)-1,3,4-thiadiazol-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， 生成 1-(2-(5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-ylamino)phenyl)-1'-neopentyl-4-(trifluoromethyl)spiro[indoline-3,4'-piperidin]-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

文献信息

• [EN] AMINO-HETEROARYL 7-HYDROXY-SPIROPIPERIDINE INDOLINYL ANTAGONISTS OF P2Y1 RECEPTOR<br/>[FR] ANTAGONISTES D'AMINO-HÉTÉROARYLE 7-HYDROXYSPIROPIPÉRIDINE INDOLINYLE DU RÉCEPTEUR P2Y1
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014022253A1

  公开（公告）日：2014-02-06

  The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are antagonists of P2Y1 receptor which may be used as medicaments.

  本发明提供了如规范中定义的Formula (I)的化合物，以及包含任何此类新化合物的组合物。这些化合物是P2Y1受体的拮抗剂，可用作药物。
• AMINO-HETEROARYL 7-HYDROXY-SPIROPIPERIDINE INDOLINYL ANTAGONISTS OF P2Y1 RECEPTOR
  申请人：Bristol-Myers Squibb Company

  公开号：EP2880034B1

  公开（公告）日：2016-06-22
• US9120798B2
  申请人：——

  公开号：US9120798B2

  公开（公告）日：2015-09-01