CN102432447B - Cyclopentanone-containing curcumin monocarbonyl analogs and uses thereof - Google Patents

Abstract

The invention relates to curcumin structural analogues and application thereof. Curcumin is an excellent lead compound and has a plurality of pharmacological activity. Compared to curcumin, the analogues provided in the invention have a more stable monocarbonyl intermediate joining chain, and the joining chain is cyclopentanone; substituents on a phenyl ring of the analogues have a specific combination. The invention also includes pharmaceutically acceptable salts of the analogues, medicinal preparations containing the analogues and application of the analogues in pharmacy. According to results of related research, the analogues can be used for treating inflammation and tumors.

Description

Cyclopentanone-containing curcumin monocarbonyl analogs and uses thereof

The present invention is a divisional application of Chinese Patent Application No. 200710066787.1.

1. Technical field

The present invention relates to a class of structural analogues of curcumin. Compared with curcumin, the structure of this type of compound only contains a carbonyl group; the present invention also relates to the preparation of such compounds, pharmaceutical preparations and their anti-inflammatory, anti-tumor aspects of use.

2. Background technology

Curcumin is an important active ingredient found in almost all ginger plants. In India, Brazil, the Philippines, Japan, South Korea and other places, there are thousands of years of edible and medicinal records. Curcumin is a compound with strong pharmacological activity and wide indications. In recent years, medicinal chemistry and pharmacology studies have found that curcumin has various pharmacological effects such as anti-inflammation, anti-tumor, anti-angiogenesis, anti-mutation, anti-bacterial, anti-virus, anti-oxidation and neuroprotection. Curcumin has entered phase I in the United States. clinical trial stage. Its anti-tumor effect includes the ability to inhibit the growth and induce apoptosis of various tumor cells in vitro and inhibit tumorigenesis in vivo; the anti-angiogenic effect of curcumin includes inhibiting the proliferation of vascular endothelial cells in vitro and inhibiting the formation and growth of capillaries in vivo; Its anti-inflammatory activity includes the release of various inflammatory factors to macrophages. It is precisely because of its anti-tumor and anti-inflammatory effects, as well as its low molecular weight and non-toxic characteristics, that curcumin was once considered to be one of the ideal chemotherapeutic drugs. However, further studies have found that curcumin has low activity in the body, low absorption in the body, fast metabolism and low bioavailability, which greatly limits its application. However, considering its exact biological activity and relatively simple molecular structure, curcumin is still an excellent lead compound for structural modification and anti-tumor drug screening. Research on the design, synthesis, evaluation and screening of curcumin analogues for sexual purposes has attracted many drug research and development institutions and drug companies.

curcumin

At present, in the structural modification and drug screening of curcumin as the lead compound, researchers have drawn many valuable conclusions, especially the types and positions of substituents on the benzene ring in the curcumin structure, β-diketone There are many studies on the influence and contribution of pharmacophore on pharmacological activity, such as partial, 4-position methylene substitution, stretching and changing of the intermediate connecting chain, and the planarity of the molecule as a whole, which are used to guide the further research and development of new curcumin drugs. is of great significance.

According to the current research on various structure-activity relationships of curcumin, it is generally believed that curcumin generates proton free radicals through its phenolic hydroxyl group and β-diketone, which blocks the oxidative free radical reaction in the body and plays an anti-oxidative role; In the lesion sites of various indications, various pharmacological effects are also exerted by eliminating free radicals. This involves two important molecular groups of curcumin: the phenolic hydroxyl group and the β-diketone moiety, where the antioxidant activity of the phenolic hydroxyl group is mainly due to the hydroxyl proton donor on the aromatic ring can block the free radical chain reaction, Its antioxidant capacity depends on the number and distribution of phenolic hydroxyl groups and the properties of other substituents on the aromatic ring; the activity of the β-diketone part is mainly produced by the easy loss of the proton of the middle methylene group. Therefore, in the case that the receptor enzymes and proteins of curcumin in the body are not completely clear, the transformation of curcumin is also mainly concentrated on these two active groups: the substituents on the 1,7-position aromatic ring Changes in position and species as well as changes in the aromatic ring, changes in the structure of β-diketones, and substitutions on the 4-position methylene group.

The structural transformation of curcumin mainly focuses on the following aspects. CN1646473A; WO2003/088927; Liebigs Ann.Chem, 1557-1569 (1985); People such as Roughley, j.Chem.Soc.Perkin 1, 2379-2388 (1973); People such as Ishida, Cancer Lett., 159.135-140 ( 2000)

①The type and position of the substituent on the benzene ring, such as:

② Substitution of 4-position methylene, such as:

③ Remove the conjugated structure, such as:

④ Generate imidazole substitutes, such as:

⑤Shorten the length of the intermediate connection chain, such as:

Through a large number of documents and patents, we found that although it is generally believed that the active groups in the structure of curcumin are its phenolic hydroxyl group and β-diketone group, in curcumin analogues that do not contain these two active groups In terms of research, it has also been found that monocarbonyl curcumin analogues that do not contain β-diketone sometimes show stronger activity, which raises doubts about the fact that the β-diketone group is an essential group for the activity of curcumin. Moreover, due to the existence of the β-diketone structure, the stability of curcumin is weak, and it has better stability only when the pH is less than 6.5.

It can be seen that the structure-activity relationship of curcumin may not be as simple as the current research, and drug screening using curcumin as a lead should not be completely based on the premise of retaining the phenolic hydroxyl group and diketone structure. Accordingly, by removing the β-diketone group, we designed a stable curcumin monocarbonyl analog; considering that the phenolic hydroxyl group is an unnecessary group, we chose nearly a variety of benzene ring substitutes as the structure we designed precursor.

On the other hand, considering the influence of the planar structure of the intermediate connecting chain on the pharmacological activity, we chose acetone, cyclopentanone and cyclohexanone as the intermediate connecting chain to study the effect of the planar space on the pharmacological activity, and the results proved that this design Play a positive role in improving the pharmacological activity.

3. Contents of the invention

According to an embodiment of the invention, the invention relates to a compound of formula I:

This type of compound is a curcumin monocarbonyl analog with acetone as the middle connecting chain, wherein R ₁ , R ₂ , R ₃ and R ₄ are independently selected from hydrogen, hydroxyl, halogen, alkoxy, alkyl, haloalkyl , Amino and Alkylamino.

According to a further embodiment of the present invention, the present invention relates to a compound of formula II:

This type of compound is a curcumin monocarbonyl analog with cyclopentanone as the middle connecting chain, wherein R ₅ , R ₆ , R ₇ and R ₈ are independently selected from hydrogen, hydroxyl, halogen, alkoxy, alkyl, Haloalkyl, amino and alkylamino.

According to a further embodiment of the present invention, the present invention relates to a compound of formula III:

This type of compound is a curcumin monocarbonyl analog with cyclohexanone as the middle connecting chain, wherein R ₅ , R ₆ , R ₇ and R ₈ are independently selected from hydrogen, hydroxyl, halogen, alkoxy, alkyl, Haloalkyl, amino and alkylamino.

According to other embodiments of the present invention, the present invention is directed to a method of treating cancer comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of the above formula. Examples of cancers that may be treated include, but are not limited to, skin cancer, small cell lung cancer, testicular cancer, lymphoma, leukemia, esophagus, stomach, colon, breast, endometrium, ovary, central nervous system cancer, liver and prostate cancer.

According to other embodiments of the present invention, the present invention relates to a method of treating inflammation comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of the above formula. Examples of inflammatory conditions that may be treated include, but are not limited to, boils, hepatitis, lymphadenitis, pneumonia, dysentery, appendicitis, and traumatic infections.

4. Description of drawings

The compounds listed here are only for better illustrating the compound classes and structural forms of the present invention, and do not limit the present invention.

Fig. 1 illustrates taking acetone as the structure of the curcumin monocarbonyl analogue (1-13) of connecting chain;

Fig. 2 illustrates taking cyclopentanone as the structure of the curcumin monocarbonyl analogue (14-28) of connecting chain;

Fig. 3 illustrates taking cyclohexanone as the structure of the curcumin monocarbonyl analogue (29-40) of connecting chain;

Figure 4 illustrates the activity of inhibiting lipopolysaccharide-induced macrophage expression of tumor necrosis factor (TNF-α) by curcumin and selected compounds;

Figure 5 illustrates the activity of inhibiting lipopolysaccharide-induced macrophages expressing interleukin (IL-6) by curcumin and selected compounds;

V. Detailed description and specific implementation of the invention

Now, the present invention will be described in more detail with reference to the accompanying drawings hereinafter, where the present invention is further elucidated. However, the invention may encompass different forms, and the embodiments set forth herein should not be considered as limiting the invention. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

Unless otherwise defined differently, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. All publications, patent applications, patents, and other references mentioned herein are hereby incorporated by reference in their entirety.

The term "alkyl" as used herein refers to a C ₁ -C ₈ alkyl group, which may be linear, branched or cyclic and saturated or unsaturated.

"Alkoxy" as used herein refers to linear, branched or cyclic and saturated or unsaturated oxyhydrocarbon chains, including, for example, methoxy, ethoxy, isopropoxy, alkene Propyloxy, tetrahydropyran-2-oxyl, phenoxy.

"Haloalkyl" as used herein refers to linear or branched chain and saturated or unsaturated alkyl substituted with halogen, including, for example, trifluoromethyl, trichloromethyl, tribromomethyl, chloroethyl , Bromoethyl.

"Alkylamino" as used herein is a monosubstituted or disubstituted linear or branched alkylamino group, including, for example, dimethylamino, diethylamino, methylamino, carboxymethylamino.

As used herein, "pharmaceutically acceptable" means that a compound or composition is suitable for administration to a patient to obtain the therapeutic effect described herein, and in view of the seriousness of the disease and the need for treatment, there are no unduly harmful side effects .

In general, the active compounds of the present invention comprise the series of structures:

(I) class compound is the curcumin monocarbonyl analogue with acetone as the middle connecting chain, wherein R ₁ , R ₂ , R ₃ and R ₄ are independently selected from hydrogen, hydroxyl, halogen, alkoxy, alkyl, Haloalkyl, amino and alkylamino.

Among the compounds of formula (I), preferred compounds are:

Wherein R ₁ is bromine, and R ₂ , R ₃ , R ₄ are hydrogen compounds;

Wherein R ₃ is fluorine, and R ₁ , R ₂ , R ₄ are hydrogen compounds;

A compound wherein R ₁ and R ₄ are hydrogen, R ₂ is methoxy, and R ₃ is hydroxyl;

A compound in which R ₁ , R ₂ , and R ₄ are hydrogen, and R ₃ is hydroxyl.

(II) class compound is the curcumin monocarbonyl analog with cyclopentanone as the middle linking chain, wherein R ₅ , R ₆ , R ₇ and R ₈ are independently selected from hydrogen, hydroxyl, halogen, alkoxy, alkane radical, haloalkyl, amino and alkylamino.

Among the compounds of formula (II), preferred compounds are:

Wherein R ₆ is bromine, and R ₅ , R ₇ , R ₈ are hydrogen compounds;

Wherein R ₅ is hydrogen, and R ₆ , R ₇ , R ₈ are methyl compounds;

A compound wherein R ₅ and R ₈ are hydrogen, R ₆ is methoxy, and R ₇ is hydroxyl;

A compound wherein R ₅ , R ₆ , and R ₈ are hydrogen, and R ₇ is hydroxyl.

(III) class compound is the curcumin monocarbonyl analogue with cyclohexanone as the middle connecting chain, wherein R ₉ , R ₁₀ , R ₁₁ and R ₁₂ are independently selected from hydrogen, hydroxyl, halogen, alkoxy, alkane radical, haloalkyl, amino and alkylamino.

Among the compounds of formula (III), preferred compounds are:

Wherein R ₉ , R ₁₀ , R ₁₂ are hydrogen, and R ₁₁ is a compound of tetrahydropyran-2-oxyl group;

Wherein R ₉ , R ₁₀ , R ₁₂ are hydrogen, and R ₁₁ is a compound of dimethylamino;

A compound wherein R ₉ and R ₁₂ are hydrogen, R ₁₀ is methoxy, and R ₁₁ is tetrahydropyran-2-oxyl;

Compounds wherein R ₉ and R ₁₂ are hydrogen, R ₁₀ is methoxy, and R ₁₁ is hydroxyl;

A compound wherein R ₉ , R ₁₀ , and R ₁₂ are hydrogen, and R ₁₁ is hydroxyl.

The preferred compounds and their pharmaceutically acceptable acid addition salts form part of the complete content of the present invention.

A. Specific Compounds

Specific compounds are shown in the accompanying drawings and descriptions of the accompanying drawings. The compounds listed here are only for better illustrating the compound categories and structural forms of the present invention, and do not limit the present invention.

B. Preparation of compounds

Variations in the following general synthetic procedures will be apparent to those skilled in the art in light of the present invention and are considered to be within the scope of the present invention.

Among the curcumin analogs with formula (I) shown in Fig. 1, 1, 2, 3, 4, 5, 6, 8 are raw materials with acetone and corresponding benzene ring substituents, under the catalysis of sodium methylate, stirring produced by the reaction. The feeding ratio of the two raw materials is 1:1.5-1:3, the reaction temperature is 0°C-80°C, and the reaction time is 2-10 hours. 7 and 9 are prepared by first reacting p-hydroxybenzaldehyde or vanillin with dihydropyran, and then condensing the product with acetone. 10 and 11 were prepared by hydrolyzing 7 and 9 respectively with p-toluenesulfonic acid as a catalyst. 12 and 13 are prepared by reacting p-hydroxybenzaldehyde or vanillin with allyl bromide, and then condensing the product with acetone. The crude products generated by all the above reactions need to be separated and purified by silica gel column chromatography to obtain pure products.

Among the curcumin analogs with formula (II) shown in Fig. 2, 14, 15, 16, 17, 18, 19, 21, 26, 27, 28 are raw materials with cyclopentanone and corresponding benzene ring substituents, Under the catalysis of sodium methoxide, it can be generated by stirring the reaction. The feeding ratio of the two raw materials is 1:1-1:3, the reaction temperature is 0°C-80°C, and the reaction time is 2-10 hours. 20 and 22 are prepared by reacting p-hydroxybenzaldehyde or vanillin with dihydropyran, and then condensing the product with cyclopentanone. 23 and 24 were prepared by hydrolyzing 20 and 22 with p-toluenesulfonic acid as a catalyst. 25 is prepared by reacting p-hydroxybenzaldehyde or vanillin with allyl bromide, and then condensing the product with cyclopentanone. The crude products generated by all the above reactions need to be separated and purified by silica gel column chromatography to obtain pure products.

Among the curcumin analogs with formula (III) shown in Fig. 3, 29, 30, 31, 32, 33, 34, 36 are raw materials with cyclohexanone and corresponding benzene ring substituents, under the catalysis of sodium methylate , generated by stirring the reaction. The feeding ratio of the two raw materials is 1:1-1:3, the reaction temperature is 0°C-80°C, and the reaction time is 2-10 hours. 35 and 37 are prepared by first reacting p-hydroxybenzaldehyde or vanillin with dihydropyran, and then condensing the product with cyclohexanone. 38 and 39 were prepared by hydrolyzing 35 and 37 with p-toluenesulfonic acid as a catalyst. 40 is prepared by reacting p-hydroxybenzaldehyde or vanillin with allyl bromide, and then condensing the product with cyclohexanone. The crude products generated by all the above reactions need to be separated and purified by silica gel column chromatography to obtain pure products.

C. Pharmaceutically acceptable salts and pharmaceutical preparations for anti-inflammatory or anti-tumor use

The content of the present invention also includes the pharmaceutically acceptable salts of the compounds specified in claims 1, 2, 3, 4, 5 and 6. Pharmaceutically acceptable salts are those that retain the desired biological activity of the parent compound and do not impart undesired toxicological effects. Examples of such salts include salts with inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, etc.; salts with organic acids, such as acetic acid, oxalic acid, tartaric acid, maleic acid, citric acid, ascorbic acid, etc.; and Salts formed from the anions of elements such as chlorine, bromine, and iodine.

For the curcumin monocarbonyl analogs of the present invention, it is more preferred to formulate these compounds into pharmaceutical preparations suitable for administration. The compounds of the invention can be formulated for the treatment of various conditions. In the preparation of the pharmaceutical preparations according to the invention, the compounds according to the invention and their physiologically acceptable salts or acid derivatives thereof are usually mixed with, inter alia, acceptable carriers. Of course, the carrier must be acceptable in the sense of being compatible with any other ingredients of the formulation and must not be injurious to the patient. The carrier may be solid or liquid, and is preferably formulated with the compound as a unit dosage formulation, eg a tablet, which may contain 0.5% to 95% by weight of the active compound. One or more active compounds can be added to the preparation of the present invention, and the preparation of the present invention can be prepared by any known technique in the field of pharmacy, mainly including mixing the components, optionally including one or more auxiliary agents.

Formulations of the present invention include those suitable for oral, rectal, topical, buccal, sublingual, parenteral (e.g., subcutaneous, intramuscular, intravenous) and transdermal administration, although in any given case the most suitable The route of administration will depend upon the nature and severity of the condition being treated and upon the nature of the particular active compound employed.

specific embodiment

In the following non-limiting examples, the invention is illustrated in more detail.

A.Materials and methods

Preparation of compounds 1, 2, 3, 4, 5, 6, and 8: at room temperature, dissolve 0.01 mol of the corresponding benzene ring substitute in 10 ml of absolute ethanol, slowly add 0.005 mol of dried acetone dropwise, and stir for 10 minutes ; Slowly add 18% methanol solution containing 0.005mol sodium methoxide dropwise, stir and react for 3 to 10 hours, and a yellow precipitate is formed. After the reaction, 50ml of water was added, filtered, the filter residue was washed successively with 50ml of water and 50ml of ethanol, and vacuum-dried at 30°C. The obtained crude product was purified by silica gel column chromatography (methanol:chloroform 1:13).

Compound 1, yellow powder (56.1% yield), mp 122-124°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.39 (6H, t, CH ₃ × 2), 4.10 (4H, q, O-CH ₂ ×2), 6.99(4H, m, J=7.2, Ar-H), 7.14(2H, d, J=16Hz, CH-C=O×2), 7.68～7.74(6H, m). Elemental analysis : Theoretical %C 78.23H6.88O 14.89, found %C 78.41H 7.10O 14.69; ESI-MS m/z: 322.2.

Compound 2, yellow powder (78.0% yield), mp 151-152°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 7.00 (2H, d, J=16Hz, CH-C=O×2), 7.13( 4H, m), 7.60 (4H, m), 7.70 (2H, d, J=16Hz, Ar-CH=C×2). Elemental analysis: theoretical value %C 75.55H 4.48O 5.92, measured value %C75.60H 4.43O 5.82; ESI-MS m/z: 270.1.

Compound 3, yellow powder (45.9% yield), mp 136°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 3.89 (18H, s, O-CH ₃ ×6), 6.84 (4H, s, Ar-H ), 6.98 (2H, q, J=16Hz, CH-C=O×2), 7.65 (2H, q, J=16Hz, Ar-CH=C×2). Elemental analysis: theoretical value %C 66.65H 6.32 O 27.02, found %C 66.48H 6.37O 27.11; ESI-MS m/z: 414.2

Compound 4, yellow powder (90.1% yield), mp 185°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 3.04 (12H, s, N-CH ₃ ×4), 6.69 (4H, m, J=8.4 Hz, Ar-H), 6.90 (2H, d, J=15.6Hz, C=CH-CO×2), 7.52 (4H, m, J=8.4Hz, Ar-H), 7.68 (2H, d, J =15.6Hz, Ar-CH=C×2). Elemental analysis: theoretical value %C 78.71H 7.55O 4.99, found value %C 78.80H 7.41O 4.04; ESI-MS m/z: 320.2.

Compound 5, yellow powder (88.1% yield), mp 121-123°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 3.90 (18H, s, CH ₃ × 6), 6.85 (4H, m, Ar-H ), 6.98 (2H, d, J=16Hz, CH-C=O×2), 7.66 (2H, d, J=16Hz, Ar-CH=C×2). Elemental analysis: theoretical value %C 86.75H 8.23 O 5.02, found %C 86.70H 8.17O 5.10; ESI-MS m/z: 318.2

Compound 6, yellow powder (72.2% yield), mp97°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 7.03 (2H, d, J=16Hz, C=CH-CO×2), 7.22～7.63 ( 8H, m, Ar-H), 8.09 (2H, d, J=16Hz, Ar-CH=C×2). Elemental analysis: theoretical value %C 52.08H 3.08O 4.08, measured value %C 52.00H3.13O 4.10 ; ESI-MS m/z: 391.9.

Compound 8, yellow powder (56.3% yield), mp 117°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 7.05 (2H, d, J=16Hz, C=CH-CO×2), 7.22～7.52( 8H, m, Ar-H), 7.65 (2H, d, J=16Hz, Ar-CH=C×2). Elemental analysis: theoretical value %C 52.08H 3.08O 4.08, measured value %C 52.11H3.09O 4.01 ; ESI-MS m/z: 391.9.

Preparation of Compound 7: Suspend and dissolve 0.1 mol of p-hydroxybenzaldehyde in 40 ml of dichloromethane at room temperature, add a catalytic amount of pyridinium p-toluenesulfonate as a catalyst, and slowly add 0.2 mol of 3 , the mixed solution of 4-dihydropyran and 10ml dichloromethane, stirred and reacted for 3 hours, the reaction solution was washed with ice water, NaHCO ₃ saturated solution, brine successively, dichloromethane was distilled off under reduced pressure, and yellow oily product 4 was obtained. -(tetrahydropyran-2-yl)benzaldehyde. Dissolve 0.01 mol of the above 4-(tetrahydropyran-2-yl)benzaldehyde in 10 ml of absolute ethanol, slowly add 0.05 mol of dried acetone dropwise, and stir for 10 minutes; then slowly add 0.05 mol of sodium methoxide 18% methanol solution, stirred and reacted for 3-10 hours, and a yellow precipitate was generated. After the reaction, 50ml of water was added, filtered, the filter residue was washed successively with 50ml of water and 50ml of ethanol, and vacuum-dried at 30°C. The obtained crude product was purified by silica gel column chromatography (methanol:chloroform 1:13). Yellow powder (73.2% yield), mp 146～150°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.61～1.69 (4H, m, ⁴ CH ₂ ×2), 1.72～1.78 (4H, m, ⁵ CH ₂ ×2), 1.88～1.99 (4H, m, ³ CH ₂ ×2), 3.61 (2H, m, O-CH ₂ ^e ×2), 3.88 (2H, m, O-CH ₂ ^a ×2) , 5.49 (2H, t, O-CH-O × 2), 6.95 (2H, d, J = 16Hz, C = CH-CO × 2), 7.08 (4H, m, Ar-H 2 , ₆ × 2) , 7.56 (4H, m, Ar-H _{3, 5} × 2), 7.70 (2H, d, J = 16Hz, Ar-CH = C × 2). Elemental analysis: theoretical value %C 74.63H 6.96O 18.41, measured Value %C 74.49H 6.97O 18.47; ESI-MS m/z: 434.2.

Compound 9 was prepared according to the preparation method of compound 7, except that 4-hydroxy-3-methoxybenzaldehyde (vanillin) was used instead of p-hydroxybenzaldehyde as the raw material. Yellow powder (55.7% yield), mp67°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.61～2.05 (12H, m, CH ₂ CH ₂ CH ₂ ×2), 3.63 (2H, m, O- CH ₂ ×2), 3.92 (6H, s, O-CH ₃ ×2), 5.49 (2H, s, O-CH-O × 2), 6.90 (2H, d, J=13.2Hz, C=CH- CO×2), 6.91～7.26 (6H, m, Ar-H), 7.68 (2H, d, J=16Hz, Ar-CH=C×2). Elemental analysis: theoretical value %C 70.43H 6.93O 22.64, Found %C 70.44H 6.80O 22.58; ESI-MS m/z: 494.2.

Preparation of Compound 10: Dissolve 0.01 mol of Compound 7 in 20 ml of absolute ethanol at room temperature, add a small amount of p-toluenesulfonic acid as a catalyst, stir for 10 hours, then add 100 ml of ice water to terminate the reaction, precipitate solid, filter, wash with water, and filter residue Recrystallized with ethanol/water (9:1) to obtain pure product. Yellow powder (39.2% yield), mp246～248°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 5.21 (2H, s, OH×2), 6.94 (2H, d, J=16Hz, CH-C =O×2), 6.99～7.21(4H, m, Ar-H), 7.53～7.64(6H, m, Ar-H), 7.83(2H, d, J=16Hz, Ar-CH=C×2 ). Elemental analysis: theoretical value %C 76.68H 5.30O 18.02, found value %C 76.59H 5.37O 17.99; ESI-MS m/z: 266.1.

Compound 11 was prepared according to the preparation method of compound 10, except that compound 9 was used instead of compound 7 as the starting material. Yellow powder (44.8% yield), mp90～92°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 4.11 (6H, s, O-CH ₃ × 6), 4.67 (2H, s, OH × 2) , 7.06(2H, d, J=16Hz, CH-C=O×2), 7.21～7.35(4H, m, Ar-H), 7.61～7.79(6H, m, Ar-H), 8.08(2H , d, J=16Hz, Ar-CH=C×2). Elemental analysis: theoretical value %C 69.93H 5.56O 24.51, measured value %C69.78H 5.70O 24.56; ESI-MS m/z: 326.1.

Compound 12 was prepared according to the preparation method of compound 7, except that allyl bromide was used instead of 3,4-dihydropyran as the raw material. Yellow powder (57.9% yield), mp 123～124°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 4.61 (4H, d, J=9.4Hz, O-CH ₂ ×2), 5.23～5.25 (4H , m, C=CH ₂ ×2), 5.89 (2H, m, CH=CH ₂ ×2), 6.76 (4H, d, J=10Hz, Ar-H _3,5 ×2), 7.03 (2H, d , J=15.6Hz, CH-C=O×2), 7.17(4H, d, J=10Hz, Ar-H _2,6 ×2), 7.66(2H, d, J=15.6Hz, Ar-CH= C×2). Elemental analysis: theoretical value %C 79.94H 6.40O 13.86, measured value %C 79.99H 6.51O 14.00; ESI-MS m/z: 346.2.

Compound 13 was prepared according to the preparation method of compound 9, except that allyl bromide was used instead of 3,4-dihydropyran as the starting material. Red oily liquid (88.7% yield); ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 3.89 (6H, s, O-CH ₃ × 2), 4.59 (4H, d, J=9.8Hz, O-CH ₂ ×2), 5.19～5.22 (4H, m, C=CH ₂ ×2), 5.91 (2H, m, CH=CH ₂ ×2), 7.05 (2H, d, J=15.6Hz, CH-C= O×2), 7.10～7.25 (8H, m, Ar-H), 7.89 (2H, d, J=15.6Hz, Ar-CH=C×2). Elemental analysis: theoretical value %C 73.87H 6.45O 19.68 , found %C 73.80H 6.56O 19.71; ESI-MS m/z: 406.2.

Compounds 14, 15, 16, 17, 18, 19, 21, 26, 27, and 28 were prepared according to the preparation method of compound 1, except that cyclopentanone was used instead of acetone as the raw material.

Compound 14, yellow powder (78.9% yield), mp 191-192°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.44 (6H, t, CH ₃ × 2), 3.08 (4H, t, CH ₂ - CH ₂ ), 4.09 (4H, q, O-CH ₂ ×2), 6.93~6.96 (4H, m), 7.54~7.57 (6H, m). Elemental analysis: theoretical value %C 79.28H 6.94O13.78, Found %C 79.33H 6.70O 13.91; ESI-MS m/z: 348.2

Compound 15, yellow powder (89.7% yield), mp237°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 3.10 (4H, t, CH ₂ -CH ₂ × 2), 7.11～7.15 (4H, m, Ar-H), 7.56～7.60 (6H, m). Elemental analysis: theoretical value %C 77.01H 4.76O 5.40, measured value %C 76.90H 4.83O 5.45; ESI-MS m/z: 296.1.

Compound 16, yellow powder (86.2% yield), mp 202-204°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 3.15 (4H, m, CH ₂ -CH ₂ ), 3.91 (18H, s, O- CH ₃ ×6), 6.80～6.85 (4H, m, Ar-H), 7.53 (2H, s, Ar-CH=C×2). Elemental analysis: theoretical value %C 68.17H 6.41O 25.43, measured value% C 68.21H 6.47O 25.47; ESI-MS m/z: 440.2.

Compound 17, yellow powder (79.4% yield), mp 251°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 3.07 (12H, s, N-CH ₃ ×4), 3.18 (4H, m, CH ₂ - CH ₂ ) 6.74 (4H, m, J=9.6Hz, Ar-H), 6.99 (2H, d, J=16Hz, C=CH-CO×2), 7.71 (4H, m, J=9.6Hz, Ar -H), 7.91 (2H, d, J=16Hz, Ar-CH=C×2). Elemental analysis: theoretical value %C 79.73H 7.56O 4.62, measured value %C79.80H 7.62O 4.51; ESI-MS m /z: 346.2.

Compound 18, yellow powder (43.7% yield), mp 202-203°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 3.15 (4H, m, CH ₂ -CH ₂ ), 3.89 (18H, s, CH ₃ ×6), 6.80～6.84 (4H, m, Ar-H), 7.52 (2H, d, Ar-CH=C×2). Elemental analysis: theoretical value %C 87.16H 8.19O 4.64, measured value %C87. 17H 8.10O 4.70; ESI-MS m/z: 344.2.

Compound 19, yellow powder (54.7% yield), mp 163°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 1.93 (4H, s, CH ₂ -CH ₂ ), 7.23 (2H, m, Ar-H ₆ ×2), 7.37(2H, m, Ar-H ₄ ×2), 7.52(2H, m, Ar-H ₅ ×2), 7.66(2H, m, Ar-H ₃ ×2), 7.86(2H, s, Ar-CH=C×2). Elemental analysis: theoretical value %C 54.58H 3.37O 3.83, found value %C 54.41H 3.30O 3.94; ESI-MS m/z: 418.

Compound 21, yellow powder (66.6% yield), mp 186°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 3.12 (4H, m, CH ₂ -CH ₂ ), 7.30 (2H, m, Ar-H ₅ ×2), 7.50～7.52 (6H, m, Ar-H), 7.72 (2H, s, Ar-CH=C×2). Elemental analysis: theoretical value %C 54.58H 3.37O 3.83, measured value %C54. 68H 3.29O 3.87; ESI-MS m/z: 417.9.

Compound 26, yellow powder (65.4% yield), mp 198°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 3.05 (4H, s, CH ₂ -CH ₂ ), 7.19～7.32 (2H, m, Ar- H), 7.61～7.65 (2H, m, Ar-CH=C×2), 7.75～7.79 (4H, m, Ar-H). Elemental analysis: theoretical value %C 58.34H 2.80O3.70, measured value % C 58.61H 2.89O 3.61; ESI-MS m/z: 432.1.

Compound 27, yellow powder (63.9% yield), mp 223°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 3.03 (4H, s, CH ₂ -CH ₂ ), 7.26～7.34 (2H, m, Ar- H), 7.62～7.66 (2H, m, Ar-CH=C×2), 7.73～7.78 (4H, m). Elemental analysis: theoretical value %C 58.34H 2.80O3.70, measured value %C 58.87H 2.90 O 3.75; ESI-MS m/z: 432.7.

Compound 28, yellow powder (70.6% yield), mp 154°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.98 (4H, m, CH ₂ × 2), 2.26 (12H, s, N-CH ₃ × 4), 2.46(4H, t, CH ₂ -N×2), 3.08(4H, m, CH ₂ -CH ₂ ×2), 6.95～6.97(4H,m), 7.54～7.56(6H,m). Elemental analysis: theoretical value %C74.28H 8.31O 10.99, found value %C 74.39H 8.33O 11.17; ESI-MS m/z: 462.3.

Compound 20 was prepared according to the preparation method of compound 7, except that cyclopentanone was used instead of acetone as the raw material. Yellow powder (49.0% yield), mp 209°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.59-1.72 (8H, m, ⁴ CH ₂ ⁵ CH ₂ × 2), 1.87-1.97 (4H, m, ³ CH ₂ ×2), 3.09(4H, s, CH ₂ -CH ₂ ), 3.61(2H, m, J=5.2Hz, O-CH ₂ ^e ×2), 3.90(2H, m, J=10.7Hz , O-CH ₂ ^a ×2), 5.50(2H, t, O-CH-O×2), 7.10～7.13(4H, m, Ar-H), 7.55～7.57(6H, m). Elemental analysis: Theoretical %C75.63H 7.00O 17.37, found %C 75.70H 7.11O 17.29; ESI-MS m/z: 460.2.

Compound 22 was prepared according to the preparation method of compound 9, except that cyclopentanone was used instead of acetone as the raw material. Yellow powder (57.9% yield), mp 138°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.64～2.01 (12H, m, CH ₂ -CH ₂ -CH ₂ × 2), 3.11 (4H, m, CH ₂ -CH ₂ ×2), 3.91 (6H, s, O-CH ₃ ×2), 3.95～4.01 (4H, m, O-CH ₂ ×2), 5.50 (2H, s, O-CH-O ×2), 7.09～7.23 (6H, m, Ar-H), 7.54 (2H, s, Ar-CH=C×2). Elemental analysis: theoretical value %C 71.51H 6.97O 21.51, measured value %C 71.44 H 6.80O 21.58; ESI-MS m/z: 520.2.

Compound 23 was prepared according to the preparation method of compound 10, except that compound 20 was used instead of compound 7 as the raw material. Yellow powder (60.8% yield), mp 288°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 2.99 (4H, m, CH ₂ CH ₂ ), 4.77 (2H, s, OH×2), 6.64～6.89 (10H, m, Ar-H), 7.38 (2H, s, Ar-CH=C×2). Elemental analysis: theoretical value %C 78.06H 5.52O 16.42, measured value %C78.11H 5.47O 16.32; ESI- MS m/z: 292.1.

Compound 24 was prepared according to the preparation method of compound 10, except that compound 22 was used instead of compound 7 as the starting material. Yellow powder (59.8% yield), mp 194°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 3.13 (4H, m, CH ₂ CH ₂ ), 3.91 (6H, s, O-CH ₃ ×6), 5.01(2H, s, OH×2), 6.69～6.85(10H, m, Ar-H), 7.49(2H, s, Ar-CH=C×2). Elemental analysis: theoretical value %C 71.58H 5.72O 22.70, found %C 71.70H 5.68O 22.81; ESI-MS m/z: 352.1.

Compound 25 was prepared according to the preparation method of compound 20, except that cyclopentanone was used instead of acetone as the raw material. Yellow powder (59.7% yield), mp 192°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 3.04 (4H, m, CH ₂ CH ₂ ), 4.55 (4H, m, O-CH ₂ ×2), 5.22～5.26(4H, m, C=CH ₂ ×2), 5.73(2H, m, CH=CH ₂ ×2), 6.76～7.08(8H, m, Ar-H), 7.41(2H, s, Ar -CH=C×2). Elemental analysis: theoretical value %C 80.62H 6.49O 12.89, found value %C 80.60H 6.40O 13.00; ESI-MSm/z: 372.2.

Compounds 29, 30, 31, 32, 33, 34, 36, 41, 42, and 43 were prepared according to the preparation method of compound 1, except that cyclopentanone was used instead of acetone as the raw material.

Compound 29, yellow powder (58.9% yield), mp 147-149°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 1.56 (6H, t, CH ₃ × 2), 1.81 (2H, m, CH ₂ ) , 3.08 (4H, t, CH ₂ -CH ₂ ), 3.89 (4H, q, O-CH ₂ ×2), 6.79～7.21 (8H, m, Ar-H), 7.73 (2H, s, Ar-CH =C×2). Elemental analysis: theoretical value %C 79.53H 7.23O 13.24, found value %C 79.50H 7.40O 13.29; ESI-MS m/z: 362.2.

Compound 30, yellow powder (79.1% yield), mp 156°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 1.81 (2H, m, CH ₂ ), 2.90 (4H, t, J=5.4, =C- _CH2 ×2), 7.12(4H, m, Ar-H2, ₆ ×2), 7.45(4H, m, Ar-H3 _{, 5} ×2), 7.76(2H, s, Ar-CH=C× 2). Elemental analysis: theoretical value %C 77.29H5.19O 5.22, measured value %C 77.40H 5.20O 5.16; ESI-MS m/z: 310.1.

Compound 31, yellow powder (72.6% yield), mp 196°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 1.83 (2H, m, CH ₂ ), 2.97 (4H, t, =C-CH ₂ ×2 ), 3.90 (18H, s, O-CH ₃ ×6), 6.71 (4H, s, Ar-H), 7.73 (2H, s, Ar-CH=C × 2). Elemental analysis: theoretical value %C 68.71 H 6.65O24.64, found %C 68.79H 6.74O 24.69; ESI-MS m/z: 454.2.

Compound 32, yellow powder (80.9% yield), mp 160°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 1.82 (2H, m, CH ₂ ), 2.93 (4H, t, =C-CH ₂ ×2 ), 3.01 (12H, s, N-CH ₃ ×4), 6.72 (4H, m, Ar-H), 7.45 (4H, m, Ar-H), 7.76 (2H, s, Ar-CH=C× 2). Elemental analysis: theoretical value %C 79.96H 7.83O 4.44, measured value %C 80.12H 7.91O 4.29; ESI-MS m/z: 360.2.

Compound 33, yellow powder (88.9% yield), mp 206-208°C; ¹ HNMR (CDCl ₃ , 400 MHz) δ (ppm) 1.84 (2H, m, CH ₂ ), 2.96 (4H, t, =C-CH ₂ ×2), 3.89 (18H, s, CH ₃ ×6), 6.99 (4H, s, Ar-H), 7.73 (2H, s, Ar-CH=C×2). Elemental analysis: theoretical value %C 87.10 H 8.43O 4.46, found %C 87.01H 8.49O 4.52; ESI-MS m/z: 358.2.

Compound 34, yellow powder (76.9% yield), mp 120°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.75 (2H, m, CH ₂ ), 2.75 (4H, m, J=6.1Hz, =C -CH ₂ ), 7.18～7.35 (6H, m, Ar-H), 7.64 (2H, m, Ar-H ₆ ×2), 7.86 (2H, s, Ar-CH=C×2). Elemental analysis: Theoretical %C 55.59H3.73O 3.70, found %C 55.67H 3.60O 3.77; ESI-MS m/z: 431.9.

Compound 36, yellow powder (58.0% yield), mp 112°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.03 (2H, m, CH ₂ ), 2.90 (4H, m, J=6.1Hz, =C -CH ₂ ×2), 7.27(2H, m, Ar-H ₅ ×2), 7.30(2H, m, Ar-H ₆ ×2), 7.37(2H, m, Ar-H ₄ ×2), 7.47 (2H, s, Ar-H ₂ ×2), 7.70 (2H, s, Ar-CH=C×2). Elemental analysis: theoretical value %C 55.59H 3.73O 3.70, measured value %C55.71H 3.70O 3.81 ; ESI-MS m/z: 431.9.

Compound 35 was prepared according to the preparation method of compound 7, except that cyclohexanone was used instead of acetone as the raw material. Yellow powder (59.7% yield), mp 160°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.61～2.02 (12H, m, ³ CH ₂ ⁴ CH ₂ ⁵ CH ₂ ×2), 2.04 (2H, m , CH ₂ ), 2.92 (4H, m, = C-CH ₂ ×2), 3.62 (2H, m, J = 11.6Hz, O-CH ₂ ^e × 2), 3.90 (2H, m, J = 9.2Hz , O-CH ₂ ^a ×2), 5.48 (2H, t, O-CH-O × 2), 7.03 (4H, m, Ar-H _{2, 6} × 2), 7.43 (4H, m, Ar-H _{3, 5} × 2), 7.82 (2H, s, Ar-CH=C × 2). Elemental analysis: theoretical value %C 75.92H 7.22O 16.86, measured value %C 75.80H7.27O 16.91; ESI-MS m/ z: 474.2.

Compound 37 was prepared according to the preparation method of compound 9, except that cyclohexanone was used instead of acetone as the raw material. Yellow powder (60.0% yield), mp 138°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.65～2.04 (12H, m, CH ₂ -CH ₂ -CH ₂ × 2), 1.83 (2H, m, CH ₂ ), 2.94 (4H, t, = C-CH ₂ ×2), 3.62 (2H, d, J = 11.2Hz, O-CH ₂ ^e ×2), 3.89 (6H, s, O-CH ₃ × 2), 3.97 (2H, m, J=9.0Hz, O-CH ₂ ^a × 2), 5.47 (2H, s, O-CH-O × 2), 6.98～7.17 (6H, m, Ar-H) , 7.74 (2H, s, Ar-CH=C×2). Elemental analysis: theoretical value %C 70.43H 6.93O 22.64, found value %C 70.49H6.99O 22.37; ESI-MS m/z: 534.3.

Compound 38 was prepared according to the preparation method of compound 10, except that compound 35 was used instead of compound 7 as the starting material. Yellow powder (48.9% yield), mp269～271°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.52 (2H, m, CH ₂ ), 3.07 (4H, m, =C-CH ₂ ×2) , 4.99 (2H, s, OH×2), 6.67～6.85 (10H, m, Ar-H), 7.45 (2H, s, Ar-CH=C×2). Elemental analysis: Theoretical value %C 78.41H 5.92 O 15.67, found %C 78.40H 5.04O 15.88; ESI-MS m/z: 306.1.

Compound 39 was prepared according to the preparation method of compound 10, except that compound 37 was used instead of compound 7 as the starting material. Yellow powder (51.4% yield), mp 172～173°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.51 (2H, m, CH ₂ ), 3.01 (4H, m, =C-CH ₂ ×2) , 3.99 (6H, s, O-CH ₃ ×6), 5.10 (2H, s, OH × 2), 6.64～6.71 (10H, m, Ar-H), 7.29 (2H, s, Ar-CH=C ×2). Elemental analysis: theoretical value %C 69.93H 5.56O 24.51, measured value %C 69.78H 5.58O 24.61; ESI-MS m/z: 366.2.

Compound 40 was prepared according to the preparation method of compound 35, except that cyclopentanone was used instead of acetone as the raw material. Yellow powder (71.3% yield), mp 120～122°C; ¹ HNMR (CDCl ₃ , 400MHz) δ (ppm) 1.49 (2H, m, CH ₂ ), 2.98 (4H, m, CH ₂ CH ₂ ), 4.32 ( 4H, q, J=9.7Hz, O-CH ₂ ×2), 5.19～5.21 (4H, m, C=CH ₂ ×2), 5.62 (2H, m, CH=CH ₂ ×2), 6.65～6.70 (8H, m, Ar-H), 7.28 (2H, s, Ar-CH=C×2). Elemental analysis: theoretical value %C 80.80H 6.78O 12.42, measured value %C 80.89H 6.69O 12.45; ESI- MS m/z: 386.1.

B. Testing of anti-inflammatory activity in vitro

Macrophages derived from monocytes play an extremely important role in the initiation and course of inflammatory responses. The main difference between monocytes and macrophages is the ability to upregulate certain scavenger receptors that bind modified LDL. Modified lipoproteins taken up by macrophages can form foam proteins on the vessel wall, aggravating the polyinflammatory response by stimulating the production of inflammatory mediators (such as TNF-α and IL-6, Fig. 2). Therefore, macrophages are considered as therapeutic targets for anti-inflammatory drugs. The content of the inflammatory factors released by it is also regarded as an important means to express the anti-inflammatory activity of the test substance.

Test method: Mouse J774A.1 macrophages were treated with biological grade dimethyl sulfoxide (DMSO) and the compound of the present invention at a concentration of 10 μmol/L for 2 hours. Subsequent treatment with lipopolysaccharide (LPS, 0.5 μg/ml) induced the release of two inflammatory factors, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), secreted by macrophages for 24 hours The amount was analyzed by enzyme-linked immunoassay, and compared with the content of inflammatory factors released by J774A.1 macrophages when no drug was administered.

Results and Discussion: The results of anti-inflammatory activity in vitro are shown in Figure 4 and Figure 5 . The first data in the two figures is the blank control induced by LPS without adding any compound; the last compound is the test result of the lead curcumin. It can be seen from the two figures that most of these monocarbonyl structural analogs have stronger anti-inflammatory activity than curcumin, especially in inhibiting the release of IL-6. It indicates their possible activity in vivo, and may be developed into corresponding drugs for treating inflammation.

C. In vitro antitumor activity test

In order to illustrate that the compounds in the present invention have anti-tumor pharmacological activity, we use the MTT (tetramethyl azolium salt colorimetric method) method to test their ability to inhibit the growth of tumor cells in vitro, with IC50 (half inhibitory concentration) value Indicates the strength of their anti-tumor activity in vitro.

Test Methods:

(a) Material MTT, dissolve MTT with 0.01mol/L phosphate buffer, the final concentration is 5mg/mL, filter and sterilize, store at 4°C after aliquoting; MTT lysate, 80g of twelve Dissolve sodium alkylsulfonate in 200ml of dimethylformamide, heat to dissolve, add 200ml of distilled water, adjust the pH value to 4.7 with 80% acetic acid and 1N hydrochloric acid mixture (1:1); the choice of cell line: human Liver cancer cell line Bel-7402 and human prostate cancer cell line PC-3.

(b) Method Single cell suspension was inoculated in a 96-well plate, cultured at 37°C, 5% CO ₂ , and saturated humidity for 24 hours, with 4 parallel samples in each group; the medium was removed, and the newly prepared medium was prepared according to a series of concentrations. The solution of the tested compound, 200uL per well, was incubated for 48 hours; 20uL of 2mg/mL MTT was added to each well, and incubated for 4 hours; aspirate the culture solution in the well as completely as possible, add DMSO solution (150uL/well), shake to crystallize The substance was fully dissolved; the OD value (λ=570nm) of each well was detected by a microplate reader; the cell viability curve was drawn to obtain the IC50 value.

Result and discussion: experimental result is as shown in table 1, and the result shows that most compounds in the present invention have stronger cytotoxicity, and the activity of lead material curcumin (Cur) is much stronger, and this has not only confirmed the single compound of our design The rationality of the carbonyl structural analogs also shows that this type of compounds in the present invention may be developed into anti-tumor drugs.

Table 1: IC50 values (μg/ml) of some compounds in the present invention to Bel-7402 and PC-3 cells

Claims (3)

1. the compound or its pharmacy acceptable salt that are used for the treatment of the formula II of inflammation:

Wherein, R ₅h, R ₆h, R ₇be

and R ₈h;

Perhaps, R ₅h, R ₆oCH ₃, R ₇be

and R ₈h;

Perhaps, R ₅h, R ₆h, R ₇oCH ₂cH=CH ₂, and R ₈h;

Perhaps, R ₅cF ₃, R ₆f, R ₇h, and R ₈h;

Perhaps, R ₅f, R ₆cF ₃, R ₇h, and R ₈h;

Perhaps, R ₅h, R ₆h, R ₇be

and R ₈h.

2. the pharmaceutical preparation that is used for the treatment of inflammation, it contains compound or its pharmacy acceptable salt that claim 1 limits in a kind of pharmaceutically acceptable carrier.

3. the application in the medicine for the preparation of the treatment inflammation of the compound that claim 1 limits or its pharmacy acceptable salt.

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