Miazine compounds, intermediates of miazine compounds, preparation method of intermediates and miazine compounds as well as application of miazine compound

A compound, pyrimidine technology, applied in the field of medicinal chemical synthesis

Inactive Publication Date: 2013-04-03
SHANGHAI INST OF PHARMA IND CO LTD
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to literature research, it is found that the 4-position of the pyrimidine ring is generally directly connected to p-fluorophenyl, and there are no reports on compounds connected through heteroatoms (such as O, S, etc.)

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
  • Miazine compounds, intermediates of miazine compounds, preparation method of intermediates and miazine compounds as well as application of miazine compound
  • Miazine compounds, intermediates of miazine compounds, preparation method of intermediates and miazine compounds as well as application of miazine compound
  • Miazine compounds, intermediates of miazine compounds, preparation method of intermediates and miazine compounds as well as application of miazine compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 12

[0086] Example 12-ethoxycarbonyl-4-methyl-2-pentenoic acid ethyl ester (F)

[0087] In a 500ml three-necked flask equipped with a water separator, add diethyl malonate (15.4g, 0.096mol), isobutyraldehyde (10.6g, 0.153mol), piperidine (0.33g, 0.004mol) and acetic acid (1.14g, 0.02mol), benzene (9.3ml), stirred and refluxed for 15h. Washed with water to neutral, washed with saturated brine, anhydrous Na 2 SO 4 Dry, filter and concentrate. Distillation under reduced pressure gave 19.5 g of a colorless oily substance, yield 94.7%, bp: 107-109° C. (3 mmHg). Literature bp: 135-137°C (27mmHg). (Cope AC, Hofmamn MC, WyckoffC, et al. Condensation reactions. II. Alkylidene cyanoacetic and malonic esters [J]. J Am Chem Soc, 1941, 63(12): 3452-3456).

Embodiment 26

[0088] Example 26-Isopropyl-2-methylthio-4-hydroxyl-5-6-dihydropyrimidin-5-ylcarboxylic acid ethyl ester (G)

[0089] In a 1L four-necked flask, add F (10.0g, 0.047mol), S-methylisothiourea sulfate (10.0g, 0.072mol), triethylamine (23.5ml, 0.17mol) and tetrahydrofuran (50ml), Stirring and reflux for 24h. The insolubles were filtered off, the mother liquor was concentrated, diluted with water (60ml), extracted with ethyl acetate, washed with saturated brine, anhydrous Na 2 SO 4 After drying, concentration and washing with petroleum ether, 7.0 g of white solid was obtained, with a yield of 58.0%. mp: 114-116°C. 1 H-NMR (400MHz, CDCl 3 )δ (ppm): 7.76 (s, 1H), 4.27-4.21 (m, 2H), 3.87 (q, 1H, J = 9.6, 4.0Hz), 3.36 (d, 1H, J = 9.2Hz), 2.42 ( s, 3H), 1.82-1.78 (m, 1H), 1.28 (t, 3H, J = 7.2Hz), 1.06 (d, 3H, J = 6.8Hz), 0.92 (d, 3H, J = 6.8Hz).

Embodiment 36

[0090] Example 36-Isopropyl-2-methylthio-4-hydroxyl-pyrimidin-5-ylcarboxylic acid ethyl ester (H)

[0091] In a 2L four-necked flask, add G (12.0g, 0.046mol), DDQ (14.0g, 0.062mol) and 1,4-dioxane (100ml), stir at room temperature for 24h, concentrate the reaction solution, and weigh Crystallized to obtain 8.2 g of white crystals, with a yield of 68.9%. mp: 152-154°C. 1 H-NMR (400MHz, CDCl 3 )δ(ppm): 12.4(brs, 1H), 4.39(q, 2H, J=6.8Hz), 3.18(t, 1H, J=6.8Hz), 2.58(s, 3H), 1.38(t, 3H, J=6.8Hz), 1.21 (d, 6H, J=6.4Hz).

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 discloses miazine compounds as shown in a formula A which is disclosed in the specification and reaction intermediate compounds as shown in formulas B, C and D, wherein X is O or S, R is H,F,C1-C3 alkyl or C1-C3 alkoxy. The invention also discloses preparation methods of the intermediates and miazine compounds and an application of the miazine compounds in preparing medicaments for inhibiting HMG-CoA reductase and / or treating hyperlipidemia diseases. Compared with the pitavastatin, osuvastatin and atorvastatin in the prior art, the 6-isopropyl-2-(N-methyl-N-sulfonyl) amino-4-substituted phenoxy (or thiphenyl) miazine compounds have better or at least comparative activity for inhibiting the HMG-CoA reductase, and can be used for treating the hyperlipidemia diseases.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and specifically relates to a class of pyrimidine compounds and their intermediates, preparation methods and applications. Background technique [0002] Since hypercholesterolemia was recognized as a major risk factor for atherosclerosis and cardiovascular disease, the research on lipid-lowering drugs has developed rapidly. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (also known as "statins") are the mainstream products of hypolipidemic drugs (Cai Zhengyan, Zhou Weicheng, HMG CoA reductase inhibitors research Progress, Chinese Journal of New Drugs, 2006, 15(22): 1907-1911). Fully synthetic statin drugs that have been marketed include fluvastatin, atorvastatin, rosuvastatin, and pitavastatin. But relative to the needs of human beings, new and more efficient drugs must be found. [0003] In the prior art, the structure of a fully synthetic stati...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/47C07D405/06A61K31/505A61P3/06
Inventor 潘竞蔡正艳周伟澄沈芳毛黎光
Owner SHANGHAI INST OF PHARMA IND CO LTD
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