2-chloro-4-methyl-6-morpholino-5-nitropyrimidine | 56035-35-9

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-chloro-4-methyl-6-morpholino-5-nitropyrimidine
• 英文别名: 4-(2-Chloro-6-methyl-5-nitropyrimidin-4-yl)morpholine
• CAS: 56035-35-9
• 化学式: C₉H₁₁ClN₄O₃
• 分子量: 258.664
• InChiKey: WDWQNGZGGWUVEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  84.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-chloro-4-methyl-6-morpholino-5-nitropyrimidine 在 一水合肼 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.83h， 生成 N-[(4-methyl-6-morpholin-4-yl-5-nitropyrimidin-2-yl)amino]formamide
  参考文献：
  名称：

  Clark, Jim; Varvounis, George; Bakavoli, Mehdi, Journal of the Chemical Society. Perkin transactions I, 1986, p. 711 - 720

  摘要：

  DOI：
• 作为产物：
  描述：

  吗啉 、 2,4-二氯-5-硝基-6-甲基嘧啶 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以99%的产率得到2-chloro-4-methyl-6-morpholino-5-nitropyrimidine
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIMIDIN DERIVATIVES AND THEIR MEDICAL USE
  [FR] DÉRIVÉS PYRIMIDINE SUBSTITUÉS ET LEUR UTILISATION MÉDICALE

  摘要：

  本申请公开了新型的替代四氢呋喃-4-基甲基嘧啶衍生物，以及它们作为调节电压门控KV7（KCNQ）钾离子通道的用途。在其他方面，本申请还公开了利用这些化合物进行治疗的方法，以及包含这些化合物的药物组合物。

  公开号：

  WO2010097379A1

文献信息

• PYRROLO[3,2-d]PYRIMIDINE COMPOUNDS AND THEIR USE AS PI3 KINASE AND mTOR KINASE INHIBITORS
  申请人：CHEN Zecheng

  公开号：US20090149458A1

  公开（公告）日：2009-06-11

  A pyrrolo[3,2-d]pyrimidine compound, such as a compound of the formula (I): or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.

  一种吡咯并[3,2-d]嘧啶化合物，例如具有以下式（I）的化合物：或其药用可接受的盐，其中构成变量如本文所定义，包括所述化合物的组合物，以及制备和使用所述化合物的方法。
• 2,4,5,6-Tetrasubstituted pyrimidines and salts thereof
  申请人：Boehringer Ingelheim GmbH

  公开号：US03975384A1

  公开（公告）日：1976-08-17

  Compounds of the formula ##SPC1## Wherein R.sub.1 is alkoxy of 1 to 3 carbon atoms, morpholino, thiomorpholino, 1-oxido-thiomorpholino, 1,1-dioxido-thiomorpholino, or ##EQU1## where A is hydrogen, alkanoyl of 1 to 4 carbon atoms, alkenoyl of 2 to 4 carbon atoms, methoxy-(alkanoyl of 1 to 4 carbon atoms), carboxyl-(alkanoyl of 1 to 4 carbon atoms), acetyl-(alkanoyl of 1 to 4 carbon atoms), methoxy-(alkenoyl of 2 to 4 carbon atoms), carboxyl-(alkenoyl of 2 to 4 carbon atoms), acetyl-(alkenoyl of 2 to 4 carbon atoms), aminocarbonyl, mono(alkyl of 1 to 4 carbon atoms)-aminocarbonyl, di-(alkyl of 1 to 4 carbon atoms)-aminocarbonyl, methoxymethylaminocarbonyl, pyridinoyl, salicyloyl, furanoyl, or (alkyl of 1 to 3 carbon atoms)-sulfonyl, R.sub.2 is morpholino, thiomorpholino, 1-oxido-thiomorpholino, 1,1-dioxido-thiomorpholino, piperazino or N'-[acetyl-(alkanoyl of 1 to 3 arbon atoms)]-piperazino, R.sub.3 is hydrogen, chlorine, bromine, nitro, cyano, formyl, acetyl or carbalkoxy of 2 to 4 carbon atoms, and R.sub.4 is hydrogen, chlorine, bromine, cyano, carbalkoxy of 2 to 4 carbon atoms, alkyl of 1 to 6 carbon atoms, mono(carbalkoxy of 2 to 4 carbon atoms)-alkyl of 1 to 6 carbon atoms, di(carbalkoxy of 2 to 4 carbon atoms)-alkyl of 1 to 6 carbon atoms, hydroxyl, allyloxy, alkoxy of 1 to 6 carbon atoms, mercapto, allylmercapto, (alkyl of 1 to 6 carbon atoms)-mercapto, 1-oxidothiomorpholino, or --NHB where B is hydrogen, alkyl of 1 to 3 carbon atoms, cyclohexyl, phenyl, chloro-phenyl, carboxy-phenyl, carbomethoxy-phenyl or pyridyl, And non-toxic, pharmacologically acceptable acid addition salts thereof; the compounds as well as the salts are useful as antithrombotics.

  化合物的公式为##SPC1##其中R.sub.1是1到3个碳原子的烷氧基，吗啡基，硫环氧基，1-氧代硫环氧基，1,1-二氧代硫环氧基或##EQU1##其中A是氢，1到4个碳原子的烷酰基，2到4个碳原子的烯酰基，甲氧基-(1到4个碳原子的烷酰基)，羧基-(1到4个碳原子的烷酰基)，乙酰基-(1到4个碳原子的烷酰基)，甲氧基-(2到4个碳原子的烯酰基)，羧基-(2到4个碳原子的烯酰基)，乙酰基-(2到4个碳原子的烯酰基)，氨基甲酰基，单(1到4个碳原子的烷基)-氨基甲酰基，双(1到4个碳原子的烷基)-氨基甲酰基，甲氧基甲基氨基甲酰基，吡啶酰基，水杨酰基，呋喃酰基或(1到3个碳原子的烷基)-磺酰基，R.sub.2是吗啡基，硫环氧基，1-氧代硫环氧基，1,1-二氧代硫环氧基，哌嗪基或N'-[乙酰-(1到3个碳原子的烷酰基)]-哌嗪基，R.sub.3是氢，氯，溴，硝基，氰基，甲酰基，乙酰基或2到4个碳原子的羧基烷氧基，R.sub.4是氢，氯，溴，氰基，2到4个碳原子的羧基烷氧基，1到6个碳原子的烷基，单(2到4个碳原子的羧基烷氧基)-1到6个碳原子的烷基，双(2到4个碳原子的羧基烷氧基)-1到6个碳原子的烷基，羟基，丙烯氧基，1到6个碳原子的烷氧基，硫醇基，丙烯硫醇基，(1到6个碳原子的烷基)-硫醇基，1-氧代硫环氧基或--NHB，其中B是氢，1到3个碳原子的烷基，环己基，苯基，氯苯基，羧基苯基，甲氧基苯基或吡啶基，以及其无毒、药理学上可接受的酸盐；这些化合物和盐作为抗血栓剂具有用处。
• Synthesis and SAR of Novel 4-Morpholinopyrrolopyrimidine Derivatives as Potent Phosphatidylinositol 3-Kinase Inhibitors
  作者：Zecheng Chen、Aranapakam M. Venkatesan、Christoph M. Dehnhardt、Semiramis Ayral-Kaloustian、Natasja Brooijmans、Robert Mallon、Larry Feldberg、Irwin Hollander、Judy Lucas、Ker Yu、Fangming Kong、Tarek S. Mansour

  DOI：10.1021/jm901783v

  日期：2010.4.22

  Significant evidence suggests that deregulation of the PI3K/Akt pathway is important in tumor progression. Mechanisms include loss of function of the tumor suppressor PTEN and high frequency of mutation of the PI3K p110 alpha isoform in human malignancies. This connection between PI3K and tumor genesis makes PI3K a promising target for cancer treatment. A series of 4-morpholinopyrrolopyrimidine derivatives were synthesized and evaluated as inhibitors of PI3K alpha and mTOR, leading to the discovery of PI3K alpha selective inhibitors (e.g., 9) and dual PI3K alpha/mTOR kinase inhibitors (e.g., 46 and 48). PI3K alpha/mTOR dual inhibitors demonstrated inhibition of tumor cell growth in vitro and in vivo and caused suppression of the pathway specific biomarkers [e.g., the phosphorylation of Akt at Thr308 (T308) and Ser473 (S473)] in the human breast cancer cell line MDA361. In addition, compound 46 demonstrated good in vivo efficacy in the MDA361 human breast tumor xenograft model.
• Synthesis of New Derivatives of 4-Methyl-3-nitro-6H-pyrimido[2,1-b]quinazoline
  作者：S. M. Banihashemi、H. Hassani、J. Lari

  DOI：10.1134/s1070428020020232

  日期：2020.2

  -Various derivatives of 2-chloro-4-methyl-5-nitropyrimidine were synthesized by the reaction of 2,4-dichloro-6-methyl-5-nitro pyrimidine with amines. The synthesized derivatives were reacted with 2-aminobenzyl alcohol in m-xylene to obtain derivatives of a novel 4-methyl-3-nitro-6H-pyrimido[2,1-b]quinazoline heterocyclic system. The composition and structure of the products was confirmed by CHN analysis, IR, H-1 NMR, and C-13 NMR spectroscopy, and mass spectrometry.
• Clark, Jim; Varvounis, George, Journal of the Chemical Society. Perkin transactions I, 1984, # 7, p. 1475 - 1481
  作者：Clark, Jim、Varvounis, George

  DOI：——

  日期：——