2-chloro-10-(3-pyridylmethyl)pyrimido[1,2-a]benzimidazol-4(10H)-one | 1430744-98-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-chloro-10-(3-pyridylmethyl)pyrimido[1,2-a]benzimidazol-4(10H)-one
• 英文别名: 2-Chloro-10-(pyridin-3-ylmethyl)pyrimido[1,2-a]benzimidazol-4-one；2-chloro-10-(pyridin-3-ylmethyl)pyrimido[1,2-a]benzimidazol-4-one
• CAS: 1430744-98-1
• 化学式: C₁₆H₁₁ClN₄O
• 分子量: 310.743
• InChiKey: DRCPTOXARYRUPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  48.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  哌嗪 、 2-chloro-10-(3-pyridylmethyl)pyrimido[1,2-a]benzimidazol-4(10H)-one 以 乙醇 为溶剂， 反应 3.0h， 以61%的产率得到2-Piperazin-1-yl-10-(pyridin-3-ylmethyl)pyrimido[1,2-a]benzimidazol-4-one
  参考文献：
  名称：

  Synthesis, in vitro antiplatelet activity and molecular modelling studies of 10-substituted 2-(1-piperazinyl)pyrimido[1,2- a ]benzimidazol-4(10 H )-ones

  摘要：

  The multistep preparation of the new 10-substituted 2-(1-piperazinyl)pyrimido[1,2-a]benzimidazol-4(10H)-ones 6a-o, and of the two isomers 10-ethyl-2-(diethylamino)pyrimido[1,2-a]benzimidazol-4(10H)-one 6p and 10-ethyl-4-(diethylamino)pyrimido[1,2-a]benzimidazol-2(10H)-one 13, as well as the in vitro evaluation of their inhibitory activity on human platelet aggregation induced in platelet-rich plasma by ADP, collagen or the Ca2+ ionophore A23187 were here described. Nine out of fifteen 2-(1-piperazinyl)derivatives (6g-o) showed good inhibitory properties towards all the platelet aggregation agonists used. Moreover, a molecular modelling study has been performed on two of the best compounds of this series (6i and 6o) to confirm in silico their interactions with the catalytic site of human platelet PDE3, using the X-ray data of the PDE3B isoform in complex with an inhibitor. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.026
• 作为产物：
  描述：

  3-氯甲基吡啶盐酸盐 在 盐酸 、 乙醇 、 水 、 sodium ethanolate 、 sodium 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 5.5h， 生成 2-chloro-10-(3-pyridylmethyl)pyrimido[1,2-a]benzimidazol-4(10H)-one
  参考文献：
  名称：

  Synthesis, in vitro antiplatelet activity and molecular modelling studies of 10-substituted 2-(1-piperazinyl)pyrimido[1,2- a ]benzimidazol-4(10 H )-ones

  摘要：

  The multistep preparation of the new 10-substituted 2-(1-piperazinyl)pyrimido[1,2-a]benzimidazol-4(10H)-ones 6a-o, and of the two isomers 10-ethyl-2-(diethylamino)pyrimido[1,2-a]benzimidazol-4(10H)-one 6p and 10-ethyl-4-(diethylamino)pyrimido[1,2-a]benzimidazol-2(10H)-one 13, as well as the in vitro evaluation of their inhibitory activity on human platelet aggregation induced in platelet-rich plasma by ADP, collagen or the Ca2+ ionophore A23187 were here described. Nine out of fifteen 2-(1-piperazinyl)derivatives (6g-o) showed good inhibitory properties towards all the platelet aggregation agonists used. Moreover, a molecular modelling study has been performed on two of the best compounds of this series (6i and 6o) to confirm in silico their interactions with the catalytic site of human platelet PDE3, using the X-ray data of the PDE3B isoform in complex with an inhibitor. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.026

文献信息

• Discovery of a Novel Chemo-Type for TAAR1 Agonism via Molecular Modeling
  作者：Giancarlo Grossi、Naomi Scarano、Francesca Musumeci、Michele Tonelli、Evgeny Kanov、Anna Carbone、Paola Fossa、Raul R. Gainetdinov、Elena Cichero、Silvia Schenone

  DOI：10.3390/molecules29081739

  日期：——

  molecular docking studies of known TAAR1 ligands, characterized by an oxazoline core, have been performed in order to identify novel promising chemo-types for the discovery of more active TAAR1 agonists. In particular, the oxazoline-based compound S18616 has been taken as a reference compound for the computational study, leading to the development of quite flat and conformationally locked ligands. The choice

  由于与 TAAR1 靶向相关的广泛药理学应用，寻找新型有效 TAAR1 配体继续引起高度关注。在此，对已知的以恶唑啉核心为特征的 TAAR1 配体进行了分子对接研究，以确定新的有前途的化学类型，以发现更具活性的 TAAR1 激动剂。特别是，基于恶唑啉的化合物S18616已被用作计算研究的参考化合物，从而导致了相当平坦且构象锁定的配体的开发。建议选择“Y 形”构象来设计 TAAR1 配体，与 ASP103 和芳香族残基（例如 PHE186、PHE195、PHE268 和 PHE267）界定的蛋白质空腔相互作用。获得的结果使我们能够初步筛选一系列内部嘧啶酮-苯并咪唑 (1a-10a) 作为靶向 TAAR1 的新型支架。基于配体 (LBCM) 和基于结构 (SBCM) 的组合计算方法建议对化合物 1a–10a 进行生物学评估，从而鉴定出衍生物 1a–3a (hTAAR1 EC50 = 526.3–657