(2R)-2-[(2-amino-5-{[(1S)-1-phenylethyl]sulfanyl}- [1,3] thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol

• 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-{[(1S)-1-phenylethyl]sulfanyl}- [1,3] thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol
• 英文别名: (2R)-2-[(2-amino-5-{[(1S)-1-phenylethyl]thio}[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol；1-Pentanol, 2-[[2-aMino-5-[[(1S)-1-phenylethyl]thio]thiazolo[4,5-d]pyriMidin-7-yl]aMino]-4-Methyl-, (2R)-；(2R)-2-[[2-amino-5-[(1S)-1-phenylethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol
• 化学式: C₁₉H₂₅N₅OS₂
• 分子量: 403.572
• InChiKey: ZMQSLMZOWVGBSM-GXTWGEPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  151
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R)-2-[(2-amino-5-{[(1S)-1-phenylethyl]sulfanyl}- [1,3] thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol 在 盐酸 、 sodium nitrite 作用下， 以 水 、 乙腈 为溶剂， 以91%的产率得到(2R)-2-[(2-chloro-5-{[(1S)-1-phenylethyl]sulfanyl}[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
• 作为产物：
  描述：

  (R)-(1-氯乙基)苯 在 N,N-二甲基甲酰胺 吡啶 、 sodium tetrahydroborate 、 溴 、 sodium hydride 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 77.5h， 生成 (2R)-2-[(2-amino-5-{[(1S)-1-phenylethyl]sulfanyl}- [1,3] thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol
  参考文献：
  名称：

  WO2006/107258

  摘要：

  公开号：

文献信息

• [EN] A PROCESS FOR THE STEREOSELECTIVE PREPARATION OF CHIRAL 2-[(HETERO)ARYLALKYLSULFANYL]PYRIMIDINES AND PRODUCTS OBTAINABLE THEREFROM<br/>[FR] PROCÉDÉ DE PRÉPARATION STÉRÉOSÉLECTIVE DE 2-[(HÉTÉRO)ARYLALKYLSULFANYL]PYRIMIDINES CHIRALES ET PRODUITS POUVANT ÊTRE OBTENUS À PARTIR DE CELLES-CI
  申请人：KANCERA AB

  公开号：WO2019219771A1

  公开（公告）日：2019-11-21

  There is provided a process for the preparation of a compound of formula I, wherein R1 and R2 each have the meanings provided in the description. There is also provided a process for the preparation of pharmaceutically-active compounds comprising the process for the preparation of compounds of formula (I).

  提供了一种制备式I化合物的方法，其中R1和R2分别具有描述中提供的含义。还提供了一种制备药用活性化合物的方法，包括制备式(I)化合物的方法。
• Novel 5-Substituted 7-Amino-[1,3]Thiazolo[4,5-D]Pyrimidine Derivatives 793
  申请人：Nordvall Gunnar

  公开号：US20080214578A1

  公开（公告）日：2008-09-04

  There are disclosed novel 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine derivatives of formula (I) wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the specification, and pharmaceutically acceptable salts thereof, together with processes for their preparation, pharmaceutical compositions comprising them and their use in therapy. The compounds of formula (I) are CX 3 CR1 receptor antagonists and are thereby particularly useful in the treatment or prophylaxis of neurodegenerative disorders, demyelinating disease, cardio- and cerebrovascular atherosclerotic disorders, peripheral artery disease, rheumatoid arthritis, pulmonary diseases such as COPD, asthma or pain.

  公开了一种新的5-取代的7-氨基-[1,3]噻唑[4,5-d]嘧啶衍生物的公式(I)，其中R1、R2、R3、R4和R5如规范中所定义，并且其药学上可接受的盐，以及其制备方法、包含它们的药物组合物和它们在治疗中的用途。公式(I)化合物是CX3CR1受体拮抗剂，因此在治疗或预防神经退行性疾病、脱髓鞘性疾病、心血管和脑血管动脉粥样硬化性疾病、周围动脉疾病、类风湿性关节炎、慢性阻塞性肺疾病、哮喘或疼痛等方面特别有用。
• Novel 5,7-Disubstituted [1,3]Thiazolo[4,5-D]Pyrimidin-2(3H)-One Derivatives 794
  申请人：Nordvall Gunnar

  公开号：US20090124637A1

  公开（公告）日：2009-05-14

  There are disclosed novel 5,7-disubstituted [1,3]thiazolo[4,5-d]pyrimidin-2(3H)-one derivatives of formula (I) [Chemical formula should be inserted here. Please see paper copy] wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the specification, and pharmaceutically acceptable salts thereof, together with processes for their preparation, pharmaceutical compositions comprising them and their use in therapy. The compounds of formula (I) are CX 3 CR 1 receptor antagonists and are thereby particularly useful in the treatment or prophylaxis of neurodegenerative disorders, demyelinating disease, cardio- and cerebrovascular atherosclerotic disorders, peripheral artery disease, rheumatoid arthritis, pulmonary diseases such as COPD, asthma or pain.

  本文揭示了新颖的5,7-二取代[1,3]噻唑并[4,5-d]嘧啶-2(3H)-酮衍生物的公式(I) [化学式应在此处插入。请参见纸质复印件]，其中R1、R2、R3、R4和R5如规范中定义的那样，以及其药学上可接受的盐，以及它们的制备方法、包含它们的制剂和它们在治疗中的用途。公式(I)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、心脑血管动脉粥样硬化性疾病、周围动脉疾病、类风湿性关节炎、COPD、哮喘或疼痛的治疗或预防中特别有用。
• 5,7-DISUBSTITUTED THIAZOLO[4,5-D]PYRIMIDINES AS CHEMOKINE INHIBITORS
  申请人：Nordvall Gunnar

  公开号：US20110092519A1

  公开（公告）日：2011-04-21

  There are disclosed novel 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine derivatives of formula (I) wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the specification, and pharmaceutically acceptable salts thereof, together with processes for their preparation, pharmaceutical compositions comprising them and their use in therapy. The compounds of formula (I) are CX 3 CR1 receptor antagonists and are thereby particularly useful in the treatment or prophylaxis of neurodegenerative disorders, demyelinating disease, cardio- and cerebrovascular atherosclerotic disorders, peripheral artery disease, rheumatoid arthritis, pulmonary diseases such as COPD, asthma or pain.

  本发明公开了一种新型的5-取代的7-氨基-[1,3]噻唑[4,5-d]嘧啶衍生物，其化学式为(I)，其中R1、R2、R3、R4和R5如规范中所定义，以及其药学上可接受的盐，以及它们的制备方法、包括它们的药物组合物和在治疗中的应用。公式(I)化合物是CX3CR1受体拮抗剂，因此在治疗或预防神经退行性疾病、脱髓鞘疾病、心血管和脑血管动脉粥样硬化疾病、周围动脉疾病、类风湿性关节炎、肺部疾病如慢性阻塞性肺疾病、哮喘或疼痛方面特别有用。
• Compounds Useful for Inhibiting Metastasis from Cancer and Methods Using Same
  申请人：Drexel University College of Medicine Philadelphia Health & Education Corporation d/b/a

  公开号：US20130156761A1

  公开（公告）日：2013-06-20

  The present invention includes compositions that are useful in preventing or treating metastasis in a subject diagnosed with cancer. The present invention also includes methods of preventing or treating metastasis in a subject diagnosed with cancer, wherein the method comprises administering to the subject in need thereof an effective amount of a pharmaceutical formulation comprising at least one pharmaceutically acceptable carrier and at least one CX 3 CR1 or fractalkine antagonist.

  本发明涉及一种对已被诊断患有癌症的受试者预防或治疗转移的有用组合物。本发明还涉及一种预防或治疗已被诊断患有癌症的受试者的转移的方法，其中该方法包括向需要该药物的受试者施用至少一种药物制剂，该药物制剂包括至少一种药用载体和至少一种CX3CR1或fractalkine拮抗剂的有效量。