7-(氯甲基)-2-甲基-5H-[1,3]噻唑并[3,2-a]嘧啶-5-酮 | 943656-55-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 7-(氯甲基)-2-甲基-5H-[1,3]噻唑并[3,2-a]嘧啶-5-酮
• 中文别名: 7-(氯甲基)-2-甲基-5H-[1,3]噻唑并[3,2-A]嘧啶-5-酮
• 英文名称: 7-(chloromethyl)-2-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one
• 英文别名: 7-(chloromethyl)-2-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one；7-(chloromethyl)-2-methyl-[1,3]thiazolo[3,2-a]pyrimidin-5-one
• CAS: 943656-55-1
• 化学式: C₈H₇ClN₂OS
• mdl: MFCD09971918
• 分子量: 214.675
• InChiKey: FNZCXIFIXPCDQH-UHFFFAOYSA-N

物化性质

• 沸点：
  333.4±44.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  58
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934100090
• 包装等级：
  II
• 危险类别：
  8
• 危险性防范说明：
  P264,P270,P271,P280,P303+P361+P353,P304+P340,P305+P351+P338,P310,P330,P331,P363,P403+P233,P501
• 危险品运输编号：
  3261
• 危险性描述：
  H302,H314

反应信息

• 作为反应物：
  描述：

  苯并咪唑 、 7-(氯甲基)-2-甲基-5H-[1,3]噻唑并[3,2-a]嘧啶-5-酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以25%的产率得到7-(1H-benzimidazol-1-ylmethyl)-2-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one
  参考文献：
  名称：

  发现2-（（1 H-苯并[ d ]咪唑-1-基）甲基）-4 H-吡啶基[1,2 - a ]嘧啶-4-酮类化合物作为新型PKM2激活剂

  摘要：

  丙酮酸激酶的M2同工型是抗肿瘤治疗的新兴目标。在这封信中，我们描述了发现2-（（1 H-苯并[ d ]咪唑-1-基）甲基）-4 H-吡啶基[1,2- a ]嘧啶-4-酮的发现，这是有力且选择性的PKM2被发现具有新型结合模式的活化剂。通过计算机辅助基于结构的药物设计，将从高通量筛选中鉴定出的原始铅优化为有效系列。该系列中的代表性化合物和文献中描述的活化剂均被用作分子工具来探测PKM2活化对癌细胞的生物学作用。我们的结果表明，单独的PKM2激活不足以改变癌细胞的代谢。

  DOI：

  10.1016/j.bmcl.2013.03.090
• 作为产物：
  描述：

  2-氨基-5-甲基噻唑 、 4-氯乙酰乙酸乙酯 在 polyphosphoric acid 作用下， 反应 1.0h， 生成 7-(氯甲基)-2-甲基-5H-[1,3]噻唑并[3,2-a]嘧啶-5-酮
  参考文献：
  名称：

  Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators (PAMs): Tuning Deactivation Kinetics via Structure-Based Design

  摘要：

  The N-methyl-D-aspartate receptor (NMDAR) is a Na+ and Ca2+ permeable ionotropic glutamate receptor that is activated by the coagonists glycine and glutamate. NMDARs are critical to synaptic signaling and plasticity, and their dysfunction has been implicated in a number of neurological disorders, including schizophrenia, depression, and Alzheimer's disease. Herein we describe the discovery of potent GluN2A-selective NMDAR positive allosteric modulators (PAMs) starting from a high-throughput screening hit. Using structure-based design, we sought to increase potency at the GluN2A subtype, while improving selectivity against related amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). The structure activity relationship of channel deactivation kinetics was studied using a combination of electrophysiology and protein crystallography. Effective incorporation of these strategies resulted in the discovery of GNE-0723 (46), a highly potent and brain penetrant GluN2A-selective NMDAR PAM suitable for in vivo characterization.

  DOI：

  10.1021/acs.jmedchem.5b02010

文献信息

• BICYCLIC HETEROARYL COMPOUNDS AS PDE10 INHIBITORS
  申请人：Verhoest R, Patrick

  公开号：US20070155779A1

  公开（公告）日：2007-07-05

  The invention pertains to bicyclic heteroaryl compounds that serve as effective phosphodiesterase (PDE) inhibitors The invention also relates to compounds which are selective inhibitors of PDE-10. The invention further relates to intermediates for preparation of such compounds; pharmaceutical compositions comprising such compounds; and the use of such compounds in methods for treating certain central nervous system (CNS) or other disorders. The invention relates also to methods for treating neurodegenerative and psychiatric disorders, for example psychosis and disorders comprising deficient cognition as a symptom.

  这项发明涉及用作有效磷酸二酯酶（PDE）抑制剂的双环杂环芳基化合物。该发明还涉及选择性抑制PDE-10的化合物。此外，该发明还涉及制备这种化合物的中间体；包含这种化合物的药物组合物；以及将这种化合物用于治疗某些中枢神经系统（CNS）或其他疾病的方法。该发明还涉及治疗神经退行性和精神障碍的方法，例如精神病和包括认知缺陷作为症状的疾病。
• FUSED PYRIMIDINEONE COMPOUNDS AS TRPV3 MODULATORS
  申请人：Lingham Prasada Rao V.S.

  公开号：US20090286811A1

  公开（公告）日：2009-11-19

  The present invention provides transient receptor potential vanilloid (TRPV) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPV3. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPV3.

  本发明提供了瞬时受体电位香草酰基（TRPV）调节剂。具体而言，本文描述的化合物对于治疗或预防TRPV3调节的疾病、病况和/或障碍非常有用。本文还提供了制备上述化合物的过程、用于合成的中间体、它们的制药组合物以及治疗或预防TRPV3调节的疾病、病况和/或障碍的方法。
• Fused pyrimidineone compounds as TRPV3 modulators
  申请人：Glenmark Pharmaceuticals S.A.

  公开号：US08119647B2

  公开（公告）日：2012-02-21

  The present invention provides transient receptor potential vanilloid (TRPV) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPV3. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPV3.

  本发明提供了瞬时受体电位香草酰基转移酶（TRPV）调节剂。特别地，本文所描述的化合物可用于治疗或预防受TRPV3调节的疾病、病况和/或疾病。本文还提供了制备所述化合物的过程，用于其合成的中间体，其制药组成物以及治疗或预防受TRPV3调节的疾病、病况和/或疾病的方法。
• Process for the preparation of fused pyrimidineone compounds useful as TRPV3 modulators
  申请人：Glenmark Pharmaceuticals S.A.

  公开号：EP2626360A1

  公开（公告）日：2013-08-14

  The present invention relates to processes for the preparation of compounds of formula (I) as well as to precursors for the preparation of compounds of formula (I).

  本发明涉及式（I）化合物的制备工艺以及制备式（I）化合物的前体。
• US8119647B2
  申请人：——

  公开号：US8119647B2

  公开（公告）日：2012-02-21