5-(benzylthio)-7-chlorothiazolo[4,5-d]pyrimidin-2-amine | 259103-38-3

• 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-(benzylthio)-7-chlorothiazolo[4,5-d]pyrimidin-2-amine
• 英文别名: 7-chloro-5-[(phenylmethyl)thio]thiazolo[4,5-d]pyrimidin-2-amine；5-(Benzylthio)-7-chloro[1,3]thiazolo[4,5-d]pyrimidin-2-amine；5-benzylsulfanyl-7-chloro-[1,3]thiazolo[4,5-d]pyrimidin-2-amine
• CAS: 259103-38-3
• 化学式: C₁₂H₉ClN₄S₂
• 分子量: 308.815
• InChiKey: SJNSPSXSWUZBQZ-UHFFFAOYSA-N

物化性质

• 沸点：
  555.5±60.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 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：
  6

反应信息

• 作为反应物：
  描述：

  5-(benzylthio)-7-chlorothiazolo[4,5-d]pyrimidin-2-amine 在 N-甲基吡咯烷酮 、 盐酸 、 sodium tetrahydroborate 、 氨 、 sodium 、 N,N-二异丙基乙胺 、 sodium nitrite 作用下， 以 水 、 二甲基亚砜 、 乙腈 为溶剂， 生成 3-{(1S)-1-[(2-chloro-7-{[(2R)-1-hydroxypentan-2-yl]amino}[1,3]thiazolo[4,5-d]pyrimidin-5-yl)sulfanyl]ethyl}benzonitrile
  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 三氯氧磷 作用下， 反应 5.0h， 以91%的产率得到5-(benzylthio)-7-chlorothiazolo[4,5-d]pyrimidin-2-amine
  参考文献：
  名称：

  [11C]甲基（2-氨基-5-（苄硫基）噻唑并[4,5-d]嘧啶-7-基）-d-亮氨酸酯的合成及初步生物学评估（CX3CR1）。

  摘要：

  参考标准（2-氨基-5-（苄硫基）噻唑并[4,5-d]嘧啶-7-基）-d-亮氨酸酯（5）及其前体2-氨基-5-（苄硫基）噻唑并[4]由6-氨基-2-巯基嘧啶丁-4-醇和BnBr合成了（5-d]嘧啶-7-基）-d-亮氨酸（6），总化学产率在5步中为7％，在6步中为4％，分别。由具有[11C]的酸前体制备目标示踪物[11C]甲基（2-氨基-5-（苄硫基）噻唑并[4,5-d]嘧啶-7-基）-d-亮氨酸酯[[11C] 5）。通过[O]-[11C]甲基化制备] CH3OTf，并根据[11C] CO2进行HPLC分离，并与SPE结合以40-50％的放射化学收率，并将衰变校正为轰击结束（EOB）。放射化学纯度> 99％，在EOB处的比活（SA）为370-1110GBq /μmol，从EOB的总合成时间约为40分钟。

  DOI：

  10.1016/j.bmcl.2017.04.052

文献信息

• [EN] NEW 2-SUBSTITUTED, 4-AMINO-THIAZOLO[4,5-D] PYRIMIDINES, USEFUL AS CHEMOKINE RECEPTOR ANTAGONISTS, ESP. CX3CR1<br/>[FR] NOUVELLES 4-AMINO-THIAZOLO[4,5-D] PYRIMIDINES SUBSTITUEES EN 2, UTILES COMME ANTAGONISTES DU RECEPTEUR CHIMIOKINE, NOTAMMENT CX3CR1
  申请人：ASTRAZENECA AB

  公开号：WO2005033115A1

  公开（公告）日：2005-04-14

  There are disclosed novel compounds of formula (I) wherein A, R1, R2, R3 and X 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 CX3CR1 receptor antagonists and are thereby particularly useful in the treatment or prophylaxis of neurodegenerative disorders, demyelinating disease, atherosclerosis and pain.

  已披露了化合物的新型结构，其化学式为(I)，其中A、R1、R2、R3和X如规范中所定义，以及其药用盐，以及它们的制备方法、包含它们的药物组合物以及它们在治疗中的应用。化合物的化学式(I)是CX3CR1受体拮抗剂，因此在神经退行性疾病、脱髓鞘疾病、动脉粥样硬化和疼痛的治疗或预防中特别有用。
• [EN] RADIOFLUORINATED 7-AMINO-5-THIO-THIAZOLO[4,5-D]PYRIMIDINES FOR IMAGING FRACTALKINE RECEPTOR (CX3CR1)<br/>[FR] 7-AMINO-5-THIO-THIAZOLO[4,5-D]PYRIMIDINES RADIOFLUORÉES À UTILISER POUR IMAGER UN RÉCEPTEUR DE LA FRACTALKINE (CX3CR1)
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2016200939A1

  公开（公告）日：2016-12-15

  Radiofluorinated 7-Amino-5-thio-thiazolo[4,5-d]pyrimidines targeting Fractalkine Receptor (CX3CR1) are disclosed. Methods of imaging CX3CR1-expressing tumors or cells also are disclosed.

  揭示了针对Fractalkine受体（CX3CR1）的放射性氟化7-氨基-5-硫代噻唑并咪啉[4,5-d]嘧啶类化合物。还公开了用于成像CX3CR1表达的肿瘤或细胞的方法。
• Thiazolopyrimidines and thier use as modulators of chemokine receptor activity
  申请人：——

  公开号：US20030032642A1

  公开（公告）日：2003-02-13

  The invention provides certain thiazolopyrimidine compound, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.

  本发明提供了某些噻唑嘧啶化合物、其制备过程和中间体、含有它们的药物组合物以及它们在治疗中的用途。
• 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。
• 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。