4,4'-(6-甲基-2,4-嘧啶二基)二吗啉 | 52026-44-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 4,4'-(6-甲基-2,4-嘧啶二基)二吗啉
• 英文名称: 2,4-dimorpholino-6-methylpyrimidine
• 英文别名: 4,4'-(6-methyl-pyrimidine-2,4-diyl)-bis-morpholine；4,4'-(6-Methylpyrimidine-2,4-diyl)dimorpholine；4-(4-methyl-6-morpholin-4-ylpyrimidin-2-yl)morpholine
• CAS: 52026-44-5
• 化学式: C₁₃H₂₀N₄O₂
• 分子量: 264.327
• InChiKey: IKUMUPPMZRMFLD-UHFFFAOYSA-N

物化性质

• 沸点：
  492.8±55.0 °C(Predicted)
• 密度：
  1.208±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  50.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  吗啉 、 2,4-二氯-6-甲基嘧啶 反应 24.0h， 以89%的产率得到4,4'-(6-甲基-2,4-嘧啶二基)二吗啉
  参考文献：
  名称：

  通过 1H 和 13C NMR 光谱中的谱线展宽效应鉴定氨基嘧啶区域异构体

  摘要：

  作为我们药物化学计划的一部分，合成了取代的单氨基和二氨基嘧啶。由于存在旋转异构体，在 4 位取代的伯胺在 1H 和 13C NMR 光谱中表现出室温谱线展宽效应，但在 2 位取代基没有观察到这些效应。这为识别区域异构体提供了一种简单的诊断工具，否则需要二维实验才能确定。

  DOI：

  10.1071/ch03316

文献信息

• [EN] TREATMENT OF NEUROLOGICAL DISORDERS<br/>[FR] TRAITEMENT DES TROUBLES NEUROLOGIQUES
  申请人：PIQUR THERAPEUTICS AG

  公开号：WO2017198346A1

  公开（公告）日：2017-11-23

  The present invention is relates to a compound of formula (I), wherein X1, X2 andX3 are, independently of each other, N or CH; with the proviso that at least two of X1X2andX3 areN; Y is N or CH; R1 and R2 are independently of each other (iii)a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fhioroalkyl, C1-C2alkoxy, C1-C2alkoxyC1-C3alkyl, CN, or C(0)0-C1- C2alkyl; or R3 and R4 form together a bivalent residue -R5R6- selected from Ci-C3alkylene optionally substituted with 1 to 4 F, -CH2-0-CH2-, -CH2-NH-CH2-, or any of the structures wherein the arrows denote the bonds in formula (II); or (iv) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence Ci-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1- C2alkoxyC1-C3alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue -R8R9- selected from C1-C3alkylene optionally substituted with 1 to 4 F, -CH2-0-CH2- or -O- CH2CH2-0-; with the proviso that at least one of R1 and R2 is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a neurological disorder in a subject.

  本发明涉及一种具有式(I)的化合物，其中X1、X2和X3独立地为N或CH；但至少两个X1、X2和X3为N；Y为N或CH；R1和R2独立地为(III)式的吗啉基，其中箭头表示式(I)中的键；且R3和R4独立地为H、C1-C3烷基，可选择地取代一个或两个OH、C1-C2氟烷基、C1-C2烷氧基、C1-C2烷氧基C1-C3烷基、CN或C(0)0-C1-C2烷基；或者R3和R4一起形成一种双价残基-R5R6-，所述残基选自C1-C3烷基，可选择地取代1至4个F，-CH2-0- -，- -NH- -，或箭头表示式(II)中的键的任何结构；或者(IV)选择自硫吗啉基和哌嗪基的饱和6元杂环环Z，可选择地取代1至3个R7；其中R7在每次出现时独立地为C1-C3烷基，可选择地取代一个或两个OH、C1-C2氟烷基、C1-C2烷氧基C1-C3烷基、C3-C6环烷基；或两个R7取代基一起形成一种双价残基-R8R9-，所述残基选自C1-C3烷基，可选择地取代1至4个F，- -0- -或-O- -0-；但至少R1和R2中的一个为式II的吗啉基；以及其前药、代谢物、互变异构体、溶剂化合物和药学上可接受的盐，用于预防或治疗受体内神经系统疾病。
• [EN] TREATMENT OF SKIN LESIONS<br/>[FR] TRAITEMENT DE LÉSIONS CUTANÉES
  申请人：PIQUR THERAPEUTICS AG

  公开号：WO2017198347A1

  公开（公告）日：2017-11-23

  The present invention is relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1 X2 and X3 are N; Y is N or CH; W is H or F; with the proviso that when W is F, then X1, X2 and X3 are N; R1 and R2 are independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxy, C1alkoxyC1-C3alkyl, CN, or C(O)O-C1-C2alkyl; or R3 and R4 form together a bivalent residue -R5R6- selected from C1-C3alkylene optionally substituted with 1 to 4 F, -CH2-O-CH2-, -CH2-NH-CH2-, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxyC1-C3alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue-R8R9- selected from Ci-C3alkylene optionally substituted with 1 to 4 F, -CH2-O-CH2- or -O-CH2CH2-O-; with the proviso that at least one of R1 and R2is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a skin lesion in a subject.

  本发明涉及一种具有式(I)的化合物，其中X1、X2和X3分别独立地为N或CH；但至少两个X1、X2和X3为N；Y为N或CH；W为H或F；但当W为F时，X1、X2和X3为N；R1和R2独立地为(i)式(II)的吗啡啉基，其中箭头表示式(I)中的键；且R3和R4独立地为H、C1-C3烷基，可选地取代一个或两个OH、C1-C2氟烷基、C1-C2烷氧基、C1烷氧基C1-C3烷基、CN或C(O)O-C1-C2烷基；或R3和R4共同形成一种双价残基-R5R6-，选择自C1-C3烷基，可选地取代1至4个F，-CH2-O- -，- -NH- -，或箭头表示式(II)中的键的任何结构；或(ii)选择自硫吗啡啉基和哌嗪基的饱和6元杂环环Z，可选地取代1至3个R7；其中R7在每次出现时独立地为C1-C3烷基，可选地取代一个或两个OH、C1-C2氟烷基、C1-C2烷氧基C1-C3烷基、C3-C6环烷基；或两个R7取代基共同形成一种双价残基-R8R9-，选择自C1-C3烷基，可选地取代1至4个F，- -O- -或-O- -O-；但至少R1和R2中的一个为式II的吗啡啉基；以及其前药、代谢物、互变异构体、溶剂化合物和药学上可接受的盐，用于预防或治疗受试者的皮肤病变。
• PYRIMIDINE DERIVATIVES 934
  申请人：Barlaam Bernard Christophe

  公开号：US20090023719A1

  公开（公告）日：2009-01-22

  A compound of formula (I) where one of A 1 , A 2 or A 3 is N, and the others are independently selected from CH or N; ring B is a fused 5 or 6-membered carbocyclic or heterocyclic which is optionally substituted as defined in the specification, and R 1 , R 2 , R 3 , R 4 , and n are as defined in the specification. The compounds are inhibitors of EphB4 or EphA2 and therefore may be useful in pharmaceutical compositions for the treatment of conditions such as cancer.

  式（I）的化合物，其中A1、A2或A3中的一个是N，其他的独立地选择自CH或N；环B是一个融合的5或6元碳环或杂环，可按规范中定义的方式取代，R1、R2、R3、R4和n如规范中定义。这些化合物是EphB4或EphA2的抑制剂，因此可能在用于治疗癌症等疾病的药物组合物中有用。
• [EN] TREATMENT OF SKIN DISORDERS<br/>[FR] TRAITEMENT DE TROUBLES CUTANÉS
  申请人：PIQUR THERAPEUTICS AG

  公开号：WO2019101853A1

  公开（公告）日：2019-05-31

  The present invention relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1X2 and X3 are N; Y is N or CH; W is H or F; with the proviso that when W is F, then X1, X2 and X3 are N; R1 and R2 are independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxy, C1-C2alkoxyC1-C3alkyl, CN, or C(0)0-C1- C2alkyl; or R3 and R4 form together a bivalent residue -R5R6- selected from C1-C3alkylene optionally substituted with 1 to 4 F, -CH2-0-CH2-, -CH2-NH-CH2-, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1- C2alkoxyC1-C3alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue -R8R9- selected from C1-C3alkylene optionally substituted with 1 to 4 F, -CH2-0-CH2- or -0- CH2CH2-0-; with the proviso that at least one of R1 and R2 is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in a method of treating a skin disorder in a subject, wherein said skin disorder is a genodermatosis, a vascular anomaly or a skin disorder selected from scleroderma, sclerodermatous chronic graft-versus-host disease, lichen sclerosus, lichen planus, lichen ruber planus and scars.

  本发明涉及公式（I）的化合物，其中X1、X2和X3是独立的N或CH；但至少两个X1X2和X3是N；Y是N或CH；W是H或F；但当W为F时，X1、X2和X3是N；R1和R2是独立的（i）公式（II）的吗啡啶基，箭头表示公式（I）中的键；其中R3和R4是独立的H、C1-C3烷基（可选地取代一个或两个OH）、C1-C2氟代烷基、C1-C2烷氧基、C1-C2烷氧基C1-C3烷基、CN或C（0）0-C1-C2烷基；或R3和R4共同形成双价残基-R5R6-，所选自C1-C3烷基（可选地取代1至4个F）、-CH2-0- -、- -NH- -或任何箭头表示公式（II）中的键的结构；或（ii）选择自硫代吗啡啶基和哌嗪基的饱和6元杂环Z，可选地取代1至3个R7；其中R7在每次出现时是独立的C1-C3烷基（可选地取代一个或两个OH）、C1-C2氟代烷基、C1-C2烷氧基C1-C3烷基、C3-C6环烷基；或两个R7取代基共同形成双价残基-R8R9-，所选自C1-C3烷基（可选地取代1至4个F）、- -0- -或-0- -0-；但至少有一个R1和R2是公式II的吗啡啶基；以及其前药、代谢产物、互变异构体、溶剂化物和在治疗主体的皮肤疾病的方法中使用的药物可接受的盐，其中所述的皮肤疾病是遗传性皮肤病、血管异常或选择自硬皮病、硬皮样慢性移植物抗宿主病、白苔样硬化、白苔样平苔藓、红斑平苔藓和疤痕的皮肤疾病。
• NOVEL PYRIMIDINE DERIVATIVES - 816
  申请人：BARLAAM Bernard Christophe

  公开号：US20090036440A1

  公开（公告）日：2009-02-05

  The invention concerns pyrimidine compounds of Formula I, or a pharmaceutically acceptable salt thereof, where A 1 , A 2 A 3 , R 1 , n, R 2 , R 3 , and R 4 are as defined in the description. The present invention also relates to processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of EphB4 kinases.

  本发明涉及公式I的嘧啶化合物或其药学上可接受的盐，其中A1，A2A3，R1，n，R2，R3和R4如描述中所定义。本发明还涉及制备这些化合物的方法，包含它们的制药组合物以及它们在制造抗增殖剂用药物中的应用，用于预防或治疗对EphB4激酶抑制敏感的肿瘤或其他增殖性疾病。