7-chloro-5-[(2,3-difluorobenzyl)sulfanyl][1,3]thiazolo[4,5-d]pyrimidin-2-amine | 259103-43-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 7-chloro-5-[(2,3-difluorobenzyl)sulfanyl][1,3]thiazolo[4,5-d]pyrimidin-2-amine
• 英文别名: 7-chloro-5-[[(2,3-difluorophenyl)methyl]thio]-thiazolo[4,5-d]pyrimidin-2-amine；7-Chloro-5-[[(2,3-difluorophenyl)methyl]thio]thiazolo[4,5-d]pyrimidin-2-amine；7-chloro-5-[(2,3-difluorophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-2-amine
• CAS: 259103-43-0
• 化学式: C₁₂H₇ClF₂N₄S₂
• 分子量: 344.796
• InChiKey: QLMDJDUGXICAGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7-chloro-5-[(2,3-difluorobenzyl)sulfanyl][1,3]thiazolo[4,5-d]pyrimidin-2-amine 在 盐酸 、 sodium tetrahydroborate 、 N,N-二异丙基乙胺 、 potassium hydroxide 、 sodium nitrite 作用下， 以 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 2.5h， 生成 (2R)-2-({5-[(2,3-difluorobenzyl)thio]-2-methoxy[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：

  2-amino-5-[(phenylmethyl)thio]thiazolo[4,5-d]pyrimidin-7(4H)-one 在 aluminum tri-bromide 、 potassium tert-butylate 、 三氯氧磷 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 80.0h， 生成 7-chloro-5-[(2,3-difluorobenzyl)sulfanyl][1,3]thiazolo[4,5-d]pyrimidin-2-amine
  参考文献：
  名称：

  Hit-to-Lead studies: The discovery of potent, orally bioavailable thiazolopyrimidine CXCR2 receptor antagonists

  摘要：

  A Hit-to-Lead optimisation programme was carried out on a high throughput screening hit, the thiazolopyrimidine 1, resulting in the discovery of the potent, orally bioavailable CXCR2 antagonist 29. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.091

文献信息

• [EN] NOVEL COMPOUND<br/>[FR] NOUVEAU COMPOSE
  申请人：ASTRAZENECA AB

  公开号：WO2004026880A1

  公开（公告）日：2004-04-01

  A compound of formula (I) and pharmaceutically acceptable salts or solvates thereof for use in therapy.

  用于治疗的式I化合物及其药学上可接受的盐或溶剂化物。
• Identification of novel chemotypes as CXCR2 antagonists via a scaffold hopping approach from a thiazolo[4,5-d]pyrimidine
  作者：Max Van Hoof、Katrijn Boon、Tom Van Loy、Dominique Schols、Wim Dehaen、Steven De Jonghe

  DOI：10.1016/j.ejmech.2022.114268

  日期：2022.5

  and evaluated for CXCR2 antagonism using binding and calcium mobilization assays. This study revealed that the triazolo[4,5-d]pyrimidine, the isoxazolo[5,4-d]pyrimidine and the pyrido[3,4-d]pyrimidine scaffolds were endowed with IC50 values below 1 μM in both assays and therefore are promising skeletons for further optimization.

  趋化因子受体 CXCR2 及其配体介导中性粒细胞迁移到炎症部位，在许多肿瘤细胞中充当生长因子并参与血管生成。此外，CXCR2 介导的骨髓来源抑制细胞的募集导致肿瘤免疫抑制。因此，CXCR2 拮抗剂是癌症免疫治疗和炎症性疾病治疗的有前景的策略。十多年前，几种噻唑[4,5- d]嘧啶被报道为有效的 CXCR2 拮抗剂。该支架的优化主要集中在环取代基上，而芳香核心大多未开发。在这项研究中，支架跳跃策略应用于未取代的噻唑基部分。制备了十四种新型双环杂芳族和脂环族系统，并使用结合和钙动员测定评估了 CXCR2 拮抗作用。该研究表明，三唑并[4,5- d ]嘧啶、异恶唑并[5,4 - d ]嘧啶和吡啶并[3,4- d ]嘧啶支架在两种测定和试验中的IC 50值均低于1 μM。因此是有前途的骨架，可以进一步优化。
• Novel compound
  申请人：Bonnert Victor Roger

  公开号：US20060100221A1

  公开（公告）日：2006-05-11

  A compound of formula (I) and pharmaceutically acceptable salts or solvates thereof for use in therapy.

  化合物式为（I）及其药学上可接受的盐或溶剂的治疗用途。
• Thiazolopyrimidines and their use as modulators of chemokine receptor activity
  申请人：Bonnert Roger

  公开号：US20060111569A1

  公开（公告）日：2006-05-25

  The invention provides certain thiazolopyrimidine compounds of formula (I) or a pharmaceutically acceptable salt or solvate there: in which: A is a group of formula (a) or (b): processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.

  该发明提供了式（I）的某些噻唑嘧啶化合物或其药学上可接受的盐或溶剂化物，其中：A是式（a）或（b）的基团：用于它们的制备的过程和中间体，含有它们的制药组合物以及它们在治疗中的应用。
• Novel thiazolo (4,5-D) pyrimidine compounds
  申请人：AstraZeneca UK Limited, a British corporation

  公开号：US20040224961A1

  公开（公告）日：2004-11-11

  The invention provides certain thiazolopyrimidine compounds of formula (I) or a pharmaceutically acceptable salt or solvate thereof; processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy. 1

  本发明提供式（I）的某些噻唑嘧啶化合物或其药学上可接受的盐或溶剂；用于它们的制备的过程和中间体，含有它们的制药组合物及其在治疗中的用途。