5-{[(1S)-1-(6-chloropyridin-3-yl)ethyl]sulfanyl}-7-{[(2R)-1-hydroxypentan-2-yl]amino}[1,3]thiazolo[4,5-d]pyrimidin-2(3H)-one

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 5-{[(1S)-1-(6-chloropyridin-3-yl)ethyl]sulfanyl}-7-{[(2R)-1-hydroxypentan-2-yl]amino}[1,3]thiazolo[4,5-d]pyrimidin-2(3H)-one
• 英文别名: 5-[(1S)-1-(6-chloropyridin-3-yl)ethylsulfanyl]-7-{[(1R)-1-(hydroxymethyl)butyl]amino}[1,3]thiazolo[4,5-d]pyrimidin-2(3H)-one；5-[(1S)-1-(6-chloropyridin-3-yl)ethyl]sulfanyl-7-[[(2R)-1-hydroxypentan-2-yl]amino]-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one
• 化学式: C₁₇H₂₀ClN₅O₂S₂
• 分子量: 425.963
• InChiKey: AIYJLSDCPRXTMD-GXSJLCMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 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 、 盐酸 、 sodium tetrahydroborate 、 氨 、 sodium 、 N,N-二异丙基乙胺 、 potassium hydroxide 、 sodium nitrite 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 、 N,N-二甲基苯胺 、 乙腈 为溶剂， 反应 99.0h， 生成 5-{[(1S)-1-(6-chloropyridin-3-yl)ethyl]sulfanyl}-7-{[(2R)-1-hydroxypentan-2-yl]amino}[1,3]thiazolo[4,5-d]pyrimidin-2(3H)-one
  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 Compounds 480
  申请人：Johansson Rolf

  公开号：US20080318981A1

  公开（公告）日：2008-12-25

  There are disclosed novel 5,7-disubstituted [1,3]thiazolo[4,5-d]pyrimidin-2(3H)-one derivatives of formula (I) wherein R 1 , R 2 , R 3 , R 4 and n 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.

  本发明公开了一种新型的5,7-二取代[1,3]噻唑并[4,5-d]嘧啶-2(3H)-酮衍生物(I)，其中R1、R2、R3、R4和n在规范中定义，以及其药学上可接受的盐，以及它们的制备方法、含有它们的制药组合物和它们在治疗中的应用。化合物(I)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性疾病、周围动脉疾病、类风湿性关节炎、COPD、哮喘或疼痛方面特别有用。
• 5,7-DISUBSTITUTED THIAZOLO[4,5-D]PYRIMIDINES FOR THE SELECTIVE INHIBITION OF CHEMOKINE RECEPTORS
  申请人：Johansson Rolf

  公开号：US20110105537A1

  公开（公告）日：2011-05-05

  There are disclosed novel 5,7-disubstituted [1,3]thiazolo[4,5-d]pyrimidin-2(3H)-one derivatives of formula (I) wherein R 1 , R 2 , R 3 , R 4 and n 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.

  本发明揭示了一种新的5,7-二取代[1,3]噻唑并[4,5-d]嘧啶-2(3H)-酮衍生物(I)，其中R1、R2、R3、R4和n如规范所定义，以及其药学上可接受的盐，还揭示了它们的制备方法、包含它们的制药组合物以及它们在治疗中的使用。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、COPD、哮喘或疼痛的治疗或预防中特别有用。
• NOVEL 5, 7-DISUBSTITUTED [1, 3]THIAZOLO [4, 5-D]PYRIMIDIN-2 (3H)-ONE DERIVATIVES AND THEIR USE IN THERAPY
  申请人：AstraZeneca AB

  公开号：EP2069364B1

  公开（公告）日：2011-12-14
• US7960395B2
  申请人：——

  公开号：US7960395B2

  公开（公告）日：2011-06-14
• [EN] NOVEL 5, 7-DISUBSTITUTED [1, 3 ] THIAZOLO [4, 5-D] PYRIMIDIN-2 (3H)-ONE DEREVATIVES AND THEIR USE IN THERAPY<br/>[FR] NOUVEAUX DÉRIVÉS DE [1, 3 ]THIAZOLO[4, 5-D]PYRIMIDINE-2(3H)-ONE 5,7-DISUBSTITUTÉS ET LEUR UTILISATION EN THÉRAPIE
  申请人：ASTRAZENECA AB

  公开号：WO2008039138A1

  公开（公告）日：2008-04-03

  [EN] There are disclosed novel 5,7-disubstituted [1,3]thiazolo[4,5-d]pyrimidin-2(3H)-one derivatives of formula (I) wherein R₁, R₂, R₃, R₄ and n 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 CX3#191CR1 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.
  [FR] L'invention concerne de nouveaux dérivés de [1,3]thiazolo[4,5-d]pyrimidine-2(3H)-one 5,7 disubstitués, représentés par la formule (I) dans laquelle R₁, R₂, R₃, R₄ et n ont les significations données dans le descriptif, des sels pharmaceutiquement acceptables de ces dérivés, des procédés de fabrication de ces composés, des compositions pharmaceutiques contenant ces composés et leur utilisation en thérapie. Les composés représentés par la formule (I) sont des antagonistes de récepteurs de CX₃CR1 et sont par conséquent particulièrement utiles dans la traitement ou la prophylaxie de troubles neurodégénératifs, de maladies de démyélinisation, de troubles athérosclérotiques cardiovasculaires et cérébrovasculaires, de maladies artérielles périphériques, de l'arthrite rhumatoïde, de maladies pulmonaires telles que COPD, de l'asthme ou de la douleur.