(2R)-2-[[2-amino-5-[(4-bromophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol | 463953-97-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (2R)-2-[[2-amino-5-[(4-bromophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol
• CAS: 463953-97-1
• 化学式: C₁₈H₂₂BrN₅OS₂
• 分子量: 468.442
• InChiKey: GCRWKKDSTSZGGK-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  151
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-amino-5-[(phenylmethyl)thio]thiazolo[4,5-d]pyrimidin-7(4H)-one 在 N-甲基吡咯烷酮 、 sodium tetrahydroborate 、 氨 、 sodium 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 水 、 二甲基亚砜 、 N,N-二甲基苯胺 为溶剂， 反应 3.0h， 生成 (2R)-2-[[2-amino-5-[(4-bromophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol
  参考文献：
  名称：

  Substituted 7-Amino-5-thio-thiazolo[4,5-d]pyrimidines as Potent and Selective Antagonists of the Fractalkine Receptor (CX₃CR1)

  摘要：

  We have developed two parallel series, A and B, of CX(3)CR1 antagonists for the treatment of multiple sclerosis. By modifying the substituents on the 7-amino-5-thio-thiazolo[4,5-d]-pyrimidine core structure, we were able to achieve compounds with high selectivity for CX(3)CR1 over the closely related CXCR2 receptor. The structure-activity relationships showed that a leucinol moiety attached to the core-structure in the 7-position together with alpha-methyl branched benzyl derivatives in the 5-position displayed promising affinity, and selectivity as well as physicochemical properties, as exemplified by compounds 18a and 24h. We show the preparation of the first potent and selective orally available CX(3)CR1 antagonists.

  DOI：

  10.1021/jm3012273

文献信息

• Novel use
  申请人：——

  公开号：US20040106628A1

  公开（公告）日：2004-06-03

  There is disclosed the use of a compound of formula (I) wherein R 1 , R 2 , R 3 , Ar and X are as defined in the specification, and pharmaceutically acceptable salts, enantiomers or racemates thereof, in the manufacture of a medicament, for the treatment or prophylaxis of diseases or conditions in which antagonism of the CX 3 CR1 receptor is beneficial. Certain novel compounds of formula (Ia) and pharmaceutically acceptable salts thereof, and enantiomers and racemates thereof are disclosed, together with processes for their preparation. The compounds of the formulae (I) and (Ia) are CX 3 CR1 receptor antagonists and are thereby particularly useful in the treatment or prophylaxis of neurodegenerative disorders, demyclinating disease and pain.

  本发明公开了使用式(I)中R1、R2、R3、Ar和X如规范中所定义的化合物及其药学上可接受的盐、对映体或外消旋体制备药物，用于治疗或预防CX3CR1受体拮抗作用有益的疾病或病况。公开了式(Ia)的某些新型化合物及其药学上可接受的盐、对映体和外消旋体，以及它们的制备方法。式(I)和(Ia)的化合物是CX3CR1受体拮抗剂，因此在神经退行性疾病、脱髓鞘疾病和疼痛的治疗或预防中特别有用。
• THIAZOLOPYRIMIDINE DERIVATIVES AND USE THEREOF AS ANTAGONISTS OF THE CX3CR1 RECEPTOR
  申请人：AstraZeneca AB

  公开号：EP1377590B1

  公开（公告）日：2007-08-15
• US7067657B2
  申请人：——

  公开号：US7067657B2

  公开（公告）日：2006-06-27
• Substituted 7-Amino-5-thio-thiazolo[4,5-<i>d</i>]pyrimidines as Potent and Selective Antagonists of the Fractalkine Receptor (CX₃CR1)
  作者：Sofia Karlström、Gunnar Nordvall、Daniel Sohn、Andreas Hettman、Dominika Turek、Kristofer Åhlin、Annika Kers、Martina Claesson、Can Slivo、Yvonne Lo-Alfredsson、Carl Petersson、Galina Bessidskaia、Per H. Svensson、Tobias Rein、Eva Jerning、Åsa Malmberg、Charlotte Ahlgen、Colin Ray、Lauri Vares、Vladimir Ivanov、Rolf Johansson

  DOI：10.1021/jm3012273

  日期：2013.4.25

  We have developed two parallel series, A and B, of CX(3)CR1 antagonists for the treatment of multiple sclerosis. By modifying the substituents on the 7-amino-5-thio-thiazolo[4,5-d]-pyrimidine core structure, we were able to achieve compounds with high selectivity for CX(3)CR1 over the closely related CXCR2 receptor. The structure-activity relationships showed that a leucinol moiety attached to the core-structure in the 7-position together with alpha-methyl branched benzyl derivatives in the 5-position displayed promising affinity, and selectivity as well as physicochemical properties, as exemplified by compounds 18a and 24h. We show the preparation of the first potent and selective orally available CX(3)CR1 antagonists.