2-(ortho-chlorobenzylthio)-6-aminouracil | 333411-14-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(ortho-chlorobenzylthio)-6-aminouracil
• 英文别名: 6-amino-2-(2-chlorobenzylsulfanyl)-3H-pyrimidin-4-one；6-Amino-2-[(2-chlorobenzyl)sulfanyl]pyrimidin-4-ol；4-amino-2-[(2-chlorophenyl)methylsulfanyl]-1H-pyrimidin-6-one
• CAS: 333411-14-6
• 化学式: C₁₁H₁₀ClN₃OS
• mdl: MFCD02198051
• 分子量: 267.739
• InChiKey: SBJPKGCAELSHAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  92.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(ortho-chlorobenzylthio)-6-aminouracil 在 吡啶 、 溴 、 N,N-二异丙基乙胺 、 三氟乙酸 、 三氯氧磷 作用下， 以 二氯甲烷 、 N,N-二甲基苯胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.17h， 生成 (3S)-3-({2-amino-5-[(2-chlorobenzyl)sulfanyl][1,3]thiazolo[4,5-d]pyrimidin-7-yl}amino)-5-methylhexan-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：

  6-氨基-2-硫脲嘧啶 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以55%的产率得到2-(ortho-chlorobenzylthio)-6-aminouracil
  参考文献：
  名称：

  新的异构体2-邻位（间位和对位）氯代（溴和硝基）苄硫基6-氨基尿嘧啶

  摘要：

  已经制备了十种新的2-苄硫基-6-氨基尿嘧啶的邻，间和对位取代的衍生物。电子冲击（EI）诱导了这些化合物的质谱裂解。在精确的质量和亚稳态跃迁测量的基础上提出了断裂途径。讨论了M + -的强度与这些化合物的选定碎片离子之间的相关性。获得的数据为确定异构体奠定了基础。这些化合物的1 H和13 C NMR光谱使用异核（HETCOR）光谱结合明确地分配了化学位移。从这些光谱得到的数据可用于区分异构体。

  DOI：

  10.1002/jhet.5570380627

文献信息

• Structure Activity Relationship of 4-Amino-2-thiopyrimidine Derivatives as Platelet Aggregation Inhibitors
  作者：Barbara Cacciari、Pamela Crepaldi、Chun Yan Cheng、Elena Bossi、Giampiero Spalluto、Stephanie Federico、Kenneth A. Jacobson、Marco Cattaneo

  DOI：10.2174/1573406415666190208124534

  日期：2019.11.18

  were tested by light trasmission aggregometry (LTA) as inducers or inhibitors of platelet aggregation in citrated platelet-rich plasma (PRP). RESULTS Among the 6-amino-2-thio-3H-pyrimidin-4-one derivatives, compounds 2c and 2h displayed marked inhibitory activity, with a capability to inhibit the ADP(10-6M)-induced platelet aggregation by 91% and 87% at 10-4M concentration, respectively. Selected 4-amino-2-

  背景技术血小板聚集在动脉血栓形成中起致病作用，其与由血栓性动脉闭塞引起的常见疾病有关，例如心肌梗塞和中风。许多努力致力于开发通过几种机制起作用的血小板聚集抑制剂：COX抑制剂，磷酸二酯酶抑制剂和凝血酶抑制剂的主要抗血小板家族。最近，在血小板聚集的腺苷二磷酸（ADP）激活的P2Y12和P2Y1受体（P2嘌呤能家族的G蛋白偶联受体）中已经发挥了重要作用，并且它们的抑制剂被用作潜在的治疗性抗血栓药。P2Y12抑制剂，例如氯吡格雷，普拉格雷，替卡格雷和坎格雷洛，已在临床上用于降低冠状动脉血栓形成风险并预防急性冠状动脉综合征。仍在寻找具有更好的风险获益特征的新型P2Y12抑制剂。方法几年前，我们的小组制备了一系列6-氨基-2-硫代-3H-嘧啶-4-酮衍生物，这些衍生物表现出有趣的血小板聚集抑制活性。为了探究这些化合物的构效关系并提高其抑制作用，我们合成了各种取代的6-氨基-2-硫代-3H-嘧啶-4-
• 6-Amino-2-mercapto-3H-pyrimidin-4-one derivatives as new candidates for the antagonism at the P2Y12 receptors
  作者：Pamela Crepaldi、Barbara Cacciari、Maria-Cruz Bonache、Giampiero Spalluto、Katia Varani、Pier Andrea Borea、Ivar von Kügelgen、Kristina Hoffmann、Mariateresa Pugliano、Cristina Razzari、Marco Cattaneo

  DOI：10.1016/j.bmc.2009.04.061

  日期：2009.7

  P2Y(12) plays an important role in platelet aggregation, which makes it an interesting target for antithrombotic agents. Compounds that antagonize P2Y(12) include the active metabolites of thienopyridines and molecules that are structurally related to ATP, which is an antagonist of P2Y(12). During the last few years, our group has been working on the development of P2Y(12) receptors antagonists that are based on an extremely simple chemical structure, the 6-amino-2-mercapto-3H-pyrimidin-4-one, variously substituted at the sulfur and oxygen functions. This nucleus represents the simplified combination of two known P2Y(12) antagonists: the active metabolite of the thienopyridines and ATP derivatives. The effects of the synthesized compounds were tested on ADP-induced human platelet aggregation, using light transmission aggregometry. None of the tested compounds induced platelet aggregation, while some of them, at concentration of 10 (4) M, partially inhibited platelet aggregation induced by ADP 10 (6) M. The most potent compound, 6b, antagonized the inhibitory effect of 2-methylthio-ADP on the forskolin-induced accumulation of cyclic-AMP in CHO FlpIN cells expressing recombinant human P2Y(12)-receptors. In addition, none of the tested compounds, including 6b, interfered with ligand binding to P1 receptors. Our results suggest that some of the synthesized compounds are specific antagonists of P2 receptors, and in particular of P2Y(12) and suggest that further development of this structurally new series of compounds as P2Y(12) receptors antagonists is recommended. (C) 2009 Elsevier Ltd. All rights reserved.