5-(6-(2-methoxypropan-2-yl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine | 1033740-29-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-(6-(2-methoxypropan-2-yl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine
• 英文别名: 5-[6-(2-methoxypropan-2-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amine
• CAS: 1033740-29-2
• 化学式: C₁₈H₂₂N₆O₂S
• 分子量: 386.478
• InChiKey: BRCOIQMZYMWNIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-ol 在 四(三苯基膦)钯 、 sodium hydride 、 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.5h， 生成 5-(6-(2-methoxypropan-2-yl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine
  参考文献：
  名称：

  The Design and Identification of Brain Penetrant Inhibitors of Phosphoinositide 3-Kinase α

  摘要：

  Inhibition of phosphoinositide 3-kinase (PI3K) signaling through PI3K alpha has received significant attention for its potential in cancer therapy. While the PI3K pathway is a well-established and widely pursued target for the treatment of many cancer types due to the high frequency of abnormal PI3K signaling, glioblastoma multiforme (GBM) is particularly relevant because the pathway is implicated in more than 80% of GBM cases. Herein, we report the identification of PI3K inhibitors designed to cross the blood-brain barrier (BBB) to engage their target where GBM tumors reside. We leveraged our historical experience with PI3K inhibitors to identify correlations between physicochemical properties and transporter efflux as well as metabolic stability to focus the selection of molecules for further study.

  DOI：

  10.1021/jm300867c

文献信息

• PHOSPHOINOSITIDE 3-KINASE INHIBITOR COMPOUNDS AND METHODS OF USE
  申请人：Castanedo Georgette

  公开号：US20080269210A1

  公开（公告）日：2008-10-30

  Compounds of Formulas Ia-d where X is S or O, mor is a morpholine group, and R 3 is a monocyclic heteroaryl group, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for modulating the activity of lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia-d for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  化合物Ia-d的化学式中，X为S或O，mor为吗啡啶基团，R3为单环杂芳基团，包括立体异构体、几何异构体、互变异构体、溶剂化物、代谢产物和其药学上可接受的盐，对于调节脂质激酶（包括PI3K）的活性以及治疗由脂质激酶介导的癌症等疾病具有用处。本文揭示了使用化合物Ia-d进行哺乳动物细胞中的体外、体内和原位诊断、预防或治疗此类疾病或相关病理条件的方法。
• COMPOSITIONS AND METHODS FOR POTENTIATED ACTIVITY OF BIOLOGICALY ACTIVE MOLECULES
  申请人：Merck & Co., Inc.

  公开号：EP2131848A2

  公开（公告）日：2009-12-16
• US9487533B2
  申请人：——

  公开号：US9487533B2

  公开（公告）日：2016-11-08
• [EN] RNA INTERFERENCE MEDIATED INHIBITION OF 5-ALPHA REDUCTASE AND ANDROGEN RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)<br/>[FR] INHIBITION MEDIEE PAR UNE INTERFERENCE ARN DE 5-ALPHA REDUCTASE ET EXPRESSION GENIQUE DU RECEPTEUR D'ANDROGENES FAISANT APPEL A UN PETIT ACIDE NUCLEIQUE INTERFERANT (SINA)
  申请人：SIRNA THERAPEUTICS INC

  公开号：WO2005045037A2

  公开（公告）日：2005-05-19

  This invention relates to compounds, compositions, and methods useful for modulating 5-alpha reductase (SRD5A-1, SRD5A-2) and androgen receptor (AR) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of 5-alpha reductase and androgen receptor (AR) gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of 5-alpha reductase and androgen receptor (AR) genes.
• [EN] RNA INTERFERENCE MEDIATED INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)<br/>[FR] INHIBITION PRODUITE PAR UNE INTERFÉRENCE AVEC UN ARN DE L'EXPRESSION DES GÈNES DU FACTEUR DE CROISSANCE DE L'ENDOTHÉLIUM VASCULAIRE ET DU RÉCEPTEUR DU FACTEUR DE CROISSANCE DE L'ENDOTHÉLIUM VASCULAIRE EN UTILISANT UN PETIT ACIDE NUCLÉIQUE INTERFÉRENT
  申请人：SIRNA THERAPEUTICS INC

  公开号：WO2007067981A2

  公开（公告）日：2007-06-14

  [EN] This invention relates to compounds, compositions, and methods useful for modulating VEGF and/or VEGFR gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of VEGF and/or VEGFR gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of VEGF and/or VEGFR genes. The application also relates to methods of treating diseases and conditions associated with VEGF and/or VEGFR gene expression, such as ocular diseases and conditions, including age related macular degeneration (AMD) and diabetic retinopathy, as well as providing dosing regimens and treatment protocols.
  [FR] Cette invention concerne des composés, des compositions et des procédés utiles pour moduler l'expression des gènes du VEGF et/ou du VEGFR en utilisant des petites molécules d'acide nucléique interférent (ANsi). Cette invention concerne également des composés, des compositions et des procédés utiles pour moduler l'expression et l'activité d'autres gènes impliqués dans les voies de l'expression et/ou de l'activité des gènes du VEGF et/ou du VEGFR par interférence avec un ARN (ARNi) en utilisant de petites molécules d'acide nucléique. En particulier, la présente invention concerne de petites molécules d'acide nucléique, telles que des molécules de petit acide nucléique interférent (ANsi), de petit ARN interférent (ARNsi), d'ARN double brin (ARNds), de microARN (ARNmi) et de petit ARN en épingle à cheveux (ARNsh), et des procédés utilisés pour moduler l'expression des gènes du VEGF et/ou du VEGFR. L'invention concerne également des procédés de traitement de maladies et d'affections associées à l'expression des gènes du VEGF et/ou du VEGFR, telles que des maladies et affections oculaires, dont la dégénérescence maculaire liée à l'âge (DMA) et la rétinopathie diabétique, ainsi que des régimes de dosage et des protocoles de traitement.