(8S)-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one | 1260585-10-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (8S)-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one
• 英文别名: (2S)-8-morpholino-2-(trifluoromethyl)-1,2,3,4-tetrahydropyrimido[1,2-a]pyrimidin-6-one；(S)-2-morpholin-4-yl-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one；(S)-8-(Morpholin-4-yl)-2-(trifluoromethyl)-1,2,3,4-tetrahydropyrimido[1,2-a]pyrimidin-6-one；(8S)-2-morpholin-4-yl-8-(trifluoromethyl)-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one
• CAS: 1260585-10-1
• 化学式: C₁₂H₁₅F₃N₄O₂
• 分子量: 304.272
• InChiKey: JTTWIGXDRNKQHR-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (8S)-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one 在 sodium hydride 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 17.0h， 生成 (S)-9-(2-methoxy-2-methylpropyl)-2-(morpholin-4-yl)-8-trifluoromethyl-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  PYRIMIDINONE DERIVATIVES, PREPARATION THEREOF AND PHARMACEUTICAL USE THEREOF

  摘要：

  这项发明涉及公式(Ia)或(Ib)的新产品：这些产品以所有同分异构体和盐的形式作为药物，特别是作为抗癌药物。

  公开号：

  US20130289031A1
• 作为产物：
  描述：

  2-chloro-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one 在 Chiralpak AD 作用下， 以 乙醇 、 正庚烷 为溶剂， 反应 1.5h， 生成 (8S)-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  JP5655070

  摘要：

  公开号：

文献信息

• NOVEL 1,2,3,4-TETRAHYDRO-PYRIMIDO(1,2-A)PYRIMIDIN-6-ONE DERIVATIVES, PREPARATION THEREOF, AND PHARMACEUTICAL USE THEREOF
  申请人：Bacque Eric

  公开号：US20120208810A1

  公开（公告）日：2012-08-16

  The invention relates to the novel materials of formula (I), where: R 1 is an optionally substituted L-aryl or L-heteroaryl, such that L is a single bond, alkyl, CO, or CO-alk, or L-X, with L□ being an alkyl and X being O or S; R 2 is H or alkyl; R 3 is an alkyl optionally substituted by Hal; and R 4 is Hou Hal, wherein said materials are in any isomeric form and the salts thereof, to be used as drugs.

  本发明涉及式(I)的新型材料，其中：R1是可选取的取代的L-芳基或L-杂环基，L是单键、烷基、CO或CO-烷基，或L-X，其中L□是烷基，X是O或S；R2是氢或烷基；R3是烷基，可选取卤素取代；R4是氢或卤素，所述材料以任何同分异构体形式及其盐形式作为药物。
• Pyrimidinone derivatives, preparation thereof and pharmaceutical use thereof
  申请人：Arigon Jerome

  公开号：US08815853B2

  公开（公告）日：2014-08-26

  The invention relates to novel products of formula (Ia) or (Ib): these products being in all the isomeric forms and salts as drugs, notably as anticancer drugs.

  本发明涉及公式（Ia）或（Ib）的新型产物：这些产物以所有同分异构体和盐的形式作为药物，特别是作为抗癌药物。
• 1,2,3,4-tetrahydro-pyrimido(1,2-a)pyrimidin-6-one derivatives, preparation thereof, and pharmaceutical use thereof
  申请人：Bacque Eric

  公开号：US08846670B2

  公开（公告）日：2014-09-30

  The invention relates to compounds of the formula: or their racemic, enantiomeric or diastereoisomeric isomers, or pharmaceutically acceptable salts of the compounds of formula I or the racemic, enantiomeric or diasteroisomeric isomers.

  本发明涉及以下化合物的公式：或其外消旋、对映或对映异构体，或公式I的化合物的外消旋、对映或对映异构体的药学上可接受的盐。
• Discovery of (2<i>S</i>)-8-[(3<i>R</i>)-3-Methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2<i>H</i>-pyrimido[1,2-<i>a</i>]pyrimidin-6-one: A Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors
  作者：Benoit Pasquier、Youssef El-Ahmad、Bruno Filoche-Rommé、Christine Dureuil、Florence Fassy、Pierre-Yves Abecassis、Magali Mathieu、Thomas Bertrand、Tsiala Benard、Cédric Barrière、Samira El Batti、Jean-Philippe Letallec、Véronique Sonnefraud、Maurice Brollo、Laurence Delbarre、Véronique Loyau、Fabienne Pilorge、Luc Bertin、Patrick Richepin、Jérôme Arigon、Jean-Robert Labrosse、Jacques Clément、Florence Durand、Romain Combet、Pierre Perraut、Vincent Leroy、Frédéric Gay、Dominique Lefrançois、François Bretin、Jean-Pierre Marquette、Nadine Michot、Anne Caron、Christelle Castell、Laurent Schio、Gary McCort、Hélène Goulaouic、Carlos Garcia-Echeverria、Baptiste Ronan

  DOI：10.1021/jm5013352

  日期：2015.1.8

  Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this lipid kinase in cancer maintenance and progression. Herein, we report the discovery of a series of tetrahydropyrimidopyrimidinone derivatives. Starting with hit compound 1a, medicinal chemistry optimization led to compound 31. This molecule displays potent activity, an exquisite selectivity for Vps34 with excellent properties. The X-ray crystal structure of compound 31 in human Vps34 illustrates how the unique molecular features of the morpholine synthon bestows selectivity against class I PI3Ks. This molecule exhibits suitable in vivo mouse PK parameters and induces a sustained inhibition of Vps34 upon acute administration. Compound 31 constitutes an optimized Vps34 inhibitor that could be used to investigate human cancer biology.
• NOUVEAUX DERIVES DE 1,2,3,4-TETRAHYDRO-PYRIMIDO{1,2-a}PYRIMIDIN-6-ONE,LEUR PREPARATION ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：SANOFI

  公开号：EP2448940A2

  公开（公告）日：2012-05-09