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1,1-Spironorbornane-pyrano[4,3-b]chromones and their preparation methods and applications

A technology for chromone compounds and spironorbornane, which is applied in the field of medicinal chemistry and can solve the problems of inability to obtain anti-tumor drugs and few types of compound sources.

Active Publication Date: 2021-08-10
ZUNYI MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, in the screening of anti-tumor drugs, the types of compound sources are still small, and effective anti-tumor drugs cannot be obtained.

Method used

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  • 1,1-Spironorbornane-pyrano[4,3-b]chromones and their preparation methods and applications
  • 1,1-Spironorbornane-pyrano[4,3-b]chromones and their preparation methods and applications
  • 1,1-Spironorbornane-pyrano[4,3-b]chromones and their preparation methods and applications

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preparation example Construction

[0027] The present invention also provides a preparation method of 1,1-spironorbornane-pyrano[4,3-b]chromones, comprising the following steps: 3-iodochromones, α- Bromoacetophenone compounds, norbornene, base compounds, palladium catalysts, phosphine ligands and organic solvents are mixed for a series cyclization reaction to obtain 1,1-spironorbornane-pyrano[4,3 -b] chromones;

[0028] The 3-iodochromone compound has a structure shown in formula II, and the α-bromoacetophenone compound has a structure shown in formula III,

[0029]

[0030] Among them, R 1 , R 2 , R 3 , R 4 , R 5 independently H, halogen, nitro, cyano, C 1 ~C 10 Alkyl, C 1 ~C 10 Alkoxy, aldehyde, ester, amino, heteroaryl, phenyl, alkyl-substituted phenyl or alkoxy-substituted phenyl. The reaction formula of above-mentioned series cyclization reaction is as shown in formula (1):

[0031]

[0032] Wherein, compound 1 is 3-iodochromone compound, compound 2 is α-bromoacetophenone compound, compoun...

Embodiment 1

[0048] 3-iodochromone (0.4mmol), α-bromoacetophenone (0.4mmol), norbornene (0.8mmol, 150.6mg), Pd (OPiv) 2 (Palladium pivalate) (0.04mmol, 12.3mg), P(4-F-C 6 h 4 ) 3 (Tris(4-fluorophenyl)phosphine) (0.08mmol, 25.3mg), K 3 PO 4 (0.8mmol, 169.8mg) and 2.5mL of mesitylene were added to a 4mL reaction flask, reacted at 100°C for 24h, after the reaction was completed, cooled to room temperature, and the resulting reaction solution was subjected to column chromatography (the eluent was acetic acid Ethyl ester and petroleum ether are mixed according to the ratio of 10:1 by volume), and the solution obtained by column chromatography is removed from the solvent to obtain a yellow solid with a yield of 118.5mg and a yield of 83%. After testing, its diastereoselective The sex ratio is 88:12, and the melting point is 163.2~165.0℃.

[0049] The above-mentioned yellow solid was characterized by single crystal-X-ray diffraction, and the results were as follows: figure 1 shown. Depend ...

Embodiment 2

[0056] The 3-iodochromone in Example 1 was replaced by 3-iodo-5-methoxychromone, and the other conditions were the same as in Example 1 to finally obtain a yellow solid with a yield of 80.4 mg and a yield of 52%. Its diastereoselectivity was detected to be 90:10, and its melting point was 170.8-171.2°C.

[0057] The above-mentioned yellow solid was subjected to NMR characterization, and the specific result data are as follows:

[0058] 1 H NMR (400MHz, CDCl 3 )δ(major+minor)7.83-7.81(m, 0.20H), 7.78-7.76(m, 1.80H), 7.48-7.47(m, 0.4H), 7.46-7.42(m, 3.60H), 6.94(dd , J=8.4, 0.92Hz, 1H), 6.75(d, J=8.0Hz, 1H), 6.28(s, 0.10H), 6.23(s, 0.90H), 3.96(s, 3H), 3.77(dd, J=13.4, 2.0Hz, 1H), 2.86(d, J=4.4Hz, 0.90H), 2.75(d, J=3.8Hz, 0.10H), 2.48-2.44(m, 1H), 2.29(d, J =10.8Hz, 0.20H), 1.95-1.90(t, J=11.4Hz, 1.80H), 1.76(d, J=13.2Hz, 1H), 1.51-1.42(m, 1H), 1.29-1.24(m, 2H), 1.14(d, J=9.8Hz, 1H);

[0059] 13 C NMR (100MHz, CDCl 3 )δ(major+minor) 176.0, 161.5, 160.1, 159.9, 156.9, 133...

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Abstract

The invention belongs to the technical field of medicinal chemistry. The present invention provides 1,1-spironorbornane-pyrano[4,3-b]chromone compounds, which have the structure shown in formula I. The 1,1-spironorbornane-pyrano[4,3-b]chromone compound provided by the present invention contains a potentially biologically active chromone and pyran skeleton, and is an important class of pharmaceutically active molecules. Drug screening provides a source of compounds that help advance the pharmaceutical industry. Experimental results show that the 1,1-spironorbornane-pyrano[4,3-b]chromone compound provided by the present invention has antitumor activity.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to 1,1-spironorbornane-pyrano[4,3-b]chromone compounds and their preparation methods and applications. Background technique [0002] Drug screening is a step in the modern drug development process of testing and obtaining compounds with specific physiological activity, which refers to the process of selecting a compound with higher activity on a specific target from a large number of compounds or new compounds through standardized experimental methods . The process of drug screening is essentially the process of conducting pharmacological activity experiments on compounds. With the development of drug development technology, the physiological activity experiments on new compounds have gradually changed from early confirmatory experiments to screening experiments. drug screening. In order to obtain suitable drugs, it is often necessary to synthesize a large number of ne...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D493/20A61P35/00A61K31/352
CPCA61P35/00C07B2200/13C07D493/20
Inventor 韩文勇杨思倚陈永正崔宝东万南微
Owner ZUNYI MEDICAL UNIVERSITY