Quinazoline heterocyclic compounds as well as preparation method and application thereof

An amine compound, quinazoline technology, applied in the field of medicinal chemistry, can solve the problems of few chemical types, limited clinical application, low selectivity, etc.

Inactive Publication Date: 2017-06-30
BEIJING UNIV OF TECH
View PDF2 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] So far, the relationship between the efficacy and tolerance of selective inhibitors of PI3K subtypes is still in the research stage
In addition, due to the similarities in the physical and chemical properties of key amino acid residues, there is no significant difference in the stru

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Quinazoline heterocyclic compounds as well as preparation method and application thereof
  • Quinazoline heterocyclic compounds as well as preparation method and application thereof
  • Quinazoline heterocyclic compounds as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] N 8 -Methyl-N 10 - Preparation of p-tolyl-2,3-dihydro-[1,4]dioxane[2,3-f]quinazoline-8,10-diamine

[0080] (a) Preparation of 2,3-dihydroxy-methyl benzoate

[0081]

[0082] The starting material 2,3-dihydroxy-benzoic acid (15 g, 97.3 mmol) was dissolved in methanol (150 mL) and cooled to 0 °C with stirring. Concentrated sulfuric acid (9 mL) was added dropwise to the solution. The reaction mixture was heated to reflux for 8 hours, and the reaction was completed as monitored by TLC, showing a brownish yellow color. The methanol solvent was evaporated to give a light brown oil. Add ethyl acetate and saturated NaHCO 3 solution until effervescence ceases. The aqueous phase was extracted with ethyl acetate (3x150 mL), dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a gray solid. Yield 95%.

[0083] 1 H NMR (400MHz, CDCl 3 )δ=10.90(s,1H),7.35(dd,=8.1,1.5Hz,1H),7.10(dd,J=7.9,1.4Hz,1H),6.78(t,J=8.0Hz,1H),5.81 (s...

Embodiment 2

[0124] N 10 - Preparation of p-tolyl-2,3-dihydro-[1,4]dioxane[2,3-f]quinazoline-8,10-diamine

[0125] Steps (a), (b), (c), (d), (e), (f), (g), (h), (i) are the same as in Example 1.

[0126] (j)N 10 - Preparation of p-tolyl-2,3-dihydro-[1,4]dioxane[2,3-f]quinazoline-8,10-diamine

[0127]

[0128] The intermediate 8-chloro-N-p-tolyl-2,3-dihydro-[1,4]dioxane[2,3-f]quinazoline-10- The amine was reacted with ammonia (38%) (5 eq), ethanol (2 mL) and tetrahydrofuran (2 mL). The progress of the reaction was monitored by TLC until no starting material was observed. After column chromatography, a yellow solid was obtained. Yield: 32%.

[0129] 1 H NMR (400MHz, CDCl 3 )δ=9.36(s,1H),7.53(d,J=8.4Hz,2H),7.13(d,J=8.9Hz,3H),6.98(d,J=9.0Hz,1H),4.91(s, 2H), 4.48–4.44(m,2H), 4.32–4.29(m,2H), 2.31(s,3H).

[0130] MS m / z:309.2[M+H] +

Embodiment 3

[0132] N 8 -Methyl-N 10 Preparation of -phenyl-2,3-dihydro-[1,4]dioxane[2,3-f]quinazoline-8,10-diamine

[0133] Steps (a), (b), (c), (d), (e), (f), (g), (h), are the same as in Example 1.

[0134] (i) Preparation of 8-chloro-N-phenyl-2,3-dihydro-[1,4]dioxane[2,3-f]quinazolin-10-amine

[0135]

[0136] Will dissolve in THF / H 2 8,10-Dichloro-2,3-dihydro-[1,4]dioxane[2,3-f]quinazoline (51.2mg, 0.2mmol) in O (2ml / 1ml), aniline ( 1.1 eq) and potassium acetate (25.4 mg, 0.26 mmol) were stirred at room temperature for 4 hours. Ethyl acetate was added to the mixture for extraction, the organic layer was collected, dried over anhydrous sodium sulfate, and the excess solvent was distilled off under reduced pressure to obtain a yellow solid. Yield: 98%.

[0137] MS m / z:314.1[M+H] +

[0138] (j)N 8 -Methyl-N 10 Preparation of -phenyl-2,3-dihydro-[1,4]dioxane[2,3-f]quinazoline-8,10-diamine

[0139]

[0140] The intermediate 8-chloro-N-phenyl-2,3-dihydro-[1,4]dioxane[2,3-f]...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention provides quinazoline heterocyclic compounds as well as a preparation method and an application thereof and belongs to the field of medicinal chemistry. The structural formula is shown as a formula (I) in the specification, wherein R<1> represents -H and -CH3; R<2> is defined in the specification, 8,10-dichloro-2,3-dihydro-[1,4] dioxane [2,3-f] quinazoline (IX) is prepared firstly, and then R<1> and R<2> substitution are performed. The compounds can be applied as PI3K (phosphoinositide 3-kinase) inhibitors for treating cancer.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and relates to N-substituent-10-substituent-2,3-dihydro-[1,4]dioxane[2,3-f]quinazolin-8-amine compounds and Its preparation method and application. Specifically, N-substituent-10-substituent-2,3-dihydro-[1,4]dioxane[2,3-f]quinazolin-8-amines with different substituents Compounds, methods for their preparation and use as phosphatidylinositol 3-kinase (PI3K) inhibitors for the treatment of cancer. Background technique [0002] Cancer is an important disease that threatens human life and health. According to the latest data released by the World Health Organization, there were 14.1 million new cancer patients and 8.2 million cancer-related deaths in the world in 2012; compared with the data in 2008 12.7 million and 7.6 million, respectively. There are 3.065 million new cancer cases in my country, and about 2.5 million deaths. The probability of people suffering from cancer in their lifetime is a...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D491/056A61K31/519A61K31/5377A61P35/00
CPCC07D491/056
Inventor 胡利明郭爽丁一鸣姜竹曾程初
Owner BEIJING UNIV OF TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap