α-trifluoromethyl alkenyl ester compound, preparation method and application

Abstract

The present invention belongs to the field of pharmaceutical chemicals and discloses an α-trifluoromethyl alkenyl ester compound, a preparation method and an application thereof. The α-trifluoromethyl alkenyl ester compound has a structure as shown in formula (I), wherein: R 1 Selected from polymethylene saturated alkyl and unsaturated hydrocarbon chains below C35, R 2 Select any one of #imgabs0##imgabs1#, where the wavy line indicates the connection point; the compounds provided by this invention can be used as anti-inflammatory and analgesic drugs for the treatment of acute and chronic inflammatory reactions, tissue hyperplasia, and pain. Some compounds exhibit better and longer-lasting anti-inflammatory and analgesic effects than commercially available nonsteroidal anti-inflammatory drugs. #imgabs2#

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical chemicals, and in particular to an α-trifluoromethyl alkenyl ester compound, a preparation method and application thereof. Background Art

[0002] Inflammation is one of the most important processes in the body's defenses. However, it often develops into painful or chronic diseases requiring drug treatment. Furthermore, inflammation is associated with various diseases, such as atherosclerosis, Alzheimer's disease, Parkinson's disease, rheumatoid arthritis, and diabetes. Currently, the primary medication used clinically to treat inflammation is nonsteroidal anti-inflammatory drugs (NSAIDs). However, due to the exposed carboxyl groups in most NSAIDs and their poor selectivity for COX-2 and COX-1, they have significant side effects, such as gastrointestinal toxicity (serious complications reaching 2-4% annually), renal impairment, cardiotoxicity, and platelet inhibition (increasing mortality from gastrointestinal bleeding). Consequently, current NSAIDs are insufficient to meet our medical needs. The safety of NSAIDs is a global concern. However, it is undeniable that the overall benefits of NSAID use outweigh the risks (European Medicines Agency, 2006). In particular, arthritis treatment and analgesia continue to rely heavily on NSAIDs. Therefore, it is of great significance to develop new NSAIDs with high selectivity and fewer side effects. Summary of the Invention

[0003] Activation of phospholipase A2 (PLA2) has become an important promoter in the pathogenesis of many inflammatory and neurodegenerative diseases, including multiple sclerosis and Alzheimer's disease. PLA2 activation is an important event in the inflammatory response associated with many acute and chronic neuropathies (J.Am.Chem.Soc.1986.108,3146-3147.Bioorg.Med.Chem.Lett.1997,7(11),1421-1426.). Many researchers have reported that targeting PLA2 may provide an attractive approach for treating inflammatory diseases such as asthma and rheumatoid arthritis (Nat.Med.2002,8,480-484.). In recent decades of research, researchers have gradually demonstrated that trifluoromethyl ketones, especially arachidonic acid trifluoromethyl ketone (AACOCF3), have excellent anti-inflammatory effects as PLA2 inhibitors. In summary, the design idea of ​​the present invention is to combine the anti-inflammatory activity of trifluoromethyl ketone and NSAIDs and use the splicing principle to synthesize ester prodrugs with higher activity and fewer side effects.

[0004] In order to solve the problems existing in the prior art, the present invention designs and synthesizes an α-trifluoromethyl alkenyl ester compound with good anti-inflammatory activity. Specifically, the α-trifluoromethyl alkenyl ester compound provided by the present invention has a structure shown in the following general formula (I):

[0005]

[0006] in,

[0007] R 1 Selected from saturated or unsaturated hydrocarbon groups below C35, preferably -C3H7, -C4H9, -C6H 13 ,-C7H 15 ,-C8H 17 ,-C 10 H 21 ,-C 12 H 25 ,-C 13 H 27 ,-C 14 H 29 ,-C 15 H 31 ,-C 16 H 33 ,-C 17 H 35 ,-C 18 H 37 ,-C 20 H 41 ,-(Z)-C6H 12 CH=CHC8H 17 ,-(Z)-C 11 H 22 CH=CHC8H 17 ,-(E)-C7H 14 CH=CH2,-(Z,Z)-C6H 12 CH=CHCH2CH=CHC5H 11 ,-(E,Z)-C7H 14 -CH=CHCH=CHC5H 11 ,-(Z,Z,Z,Z)-C2H4CH=CHCH2CH=CHCH2CH=CHCH2CH=C5H 11 Any of the following;

[0008] R 2 Selected from Any of the above, the wavy line is the connection position;

[0009] Preferably, the compound is selected from one of the following structural formulas:

[0010]

[0011]

[0012]

[0013]

[0014] The present invention also provides a method for preparing any of the above-mentioned α-trifluoromethyl alkenyl ester compounds (I). The synthetic route of the compound represented by the above-mentioned formula (I) is:

[0015]

[0016] In formula (II)-(I), R 1 and R 2 Same as the definition in claim 1; (R 3 ) n -F, -Cl, -Br, -CH3, -OCH3, -CF3, -OCF3, -OH, -NO2, -Ph and di- to penta-substituted combinations thereof, preferably -4-OCH3 and -2,4-(OCH3)2;

[0017] The specific synthesis method is:

[0018] In an ether solvent, preferably methyl tert-butyl ether, one equivalent of the intermediate ketone (II) is subjected to an ester-ketone exchange reaction with ethyl trifluoroacetate (2-4 times the amount of the intermediate ketone (II), preferably 4 times) under the action of sodium hydride (2-4 times the amount of the intermediate ketone (II), preferably 2 times), and the reaction temperature is 25-60°C, preferably 55°C; then, at 0-10°C, preferably 0°C, an acyl chloride (2-4 times the amount of the intermediate ketone (II), preferably 4 times) is added to the reaction system to capture the generated enolate anion, and the target product α-trifluoromethyl alkenyl ester (I) is obtained through purification.

[0019] The intermediate ketone (II) substituted with 4-OCH3 and -2,4-(OCH3)2 can be synthesized by the reaction shown below.

[0020]

[0021] The present invention also provides a use of any of the above-mentioned α-trifluoromethyl alkenyl esters, specifically for preparing anti-inflammatory and analgesic drugs.

[0022] Preferably, the drugs used in the test are, but not limited to, drugs for treating acute and chronic inflammation and pain as described in the examples.

[0023] The α-trifluoromethyl alkenyl ester compound provided by the present invention can be used as an effective ingredient in medicines for treating acute and chronic inflammation and the accompanying hyperplasia and pain.

[0024] The beneficial effects of the present invention compared with the prior art are:

[0025] The compounds provided by the invention can be used to prepare anti-inflammatory drugs and analgesics for the treatment of acute and chronic inflammatory reactions and tissue hyperplasia as well as pain. Some compounds show better anti-inflammatory and analgesic effects than commercially available non-steroidal anti-inflammatory drugs, and some compounds have longer-lasting effects than commercially available non-steroidal anti-inflammatory drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 is the cell viability assay result of compound I (aspirin series);

[0027] Figure 2 is the cell viability assay result of compound I (ibuprofen series);

[0028] Figure 3 is the cell viability assay result of compound I (naproxen series);

[0029] Figure 4 is the cell viability assay result of compound I (flurbiprofen, ketoprofen and indomethacin series);

[0030] Figure 5.1 The inhibitory effect of compound I (aspirin series) on NO release. Note: # indicates significant difference compared with the positive drug aspirin (P < 0.05);

[0031] Figure 5.2 The inhibitory effect of compound I (ibuprofen series) on NO release. Note: # indicates significant difference compared with the positive drug ibuprofen (P < 0.05);

[0032] Figure 5.3 The inhibitory effect of compound I (naproxen series) on NO release. Note: # indicates significant difference compared with the positive drug naproxen (P < 0.05);

[0033] Figure 5.4 The inhibitory effect of compound I (flurbiprofen series) on NO release. Note: # indicates significant difference compared with the positive drug flurbiprofen (P < 0.05);

[0034] Figure 5.5The inhibitory effect of compound I (ketoprofen and indomethacin series) on NO release. Note: # indicates significant difference compared with the positive drug ketoprofen (P < 0.05);

[0035] Figure 6 Compound (I) inhibits granulation proliferation induced by cotton ball implantation in mice. Note: * indicates significant difference compared with vehicle group (model); # indicates significant difference compared with positive drug ibuprofen group, P<0.05;

[0036] Figure 7 The results show that compound (I) inhibited writhing in mice induced by acetic acid. Note: * indicates that the effect was significant compared with the model group, and # indicates that the effect was significant compared with the positive drug ibuprofen (P<0.05). DETAILED DESCRIPTION

[0037] In order to enable those skilled in the art to better understand and implement the technical solution of the present invention, the present invention is further described below with reference to specific embodiments, but the embodiments do not limit the present invention in any way.

[0038] Unless otherwise specified, the experimental methods described in the following examples are conventional methods; the reagents and materials described are all commercially available unless otherwise specified.

[0039] The structures, physical properties and 1 HNMR data, but the present invention is not limited to these compounds.

[0040] I-1: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ8.13(d,J=7.8Hz,1H,ArH),7.69-7.62(m,1H,ArH),7.41-7.35(m,1H,ArH),7.17(d,J=8.1Hz,1H,ArH),6.17(t,J=7. 6Hz,1H,C=CH),2.33(s,3H,COCH3),2.10-2.00(m,2H,CH2),1.48-1.39(m,2H,CH2),1.33-1.21(m,6H,(CH2)3),0.87(t,J=6.6Hz,3H,CH3). 13C NMR (101 MHz, CDCl3) δ 169.5, 160.9, 151.4, 135.1, 134.5 (q, J = 36.3 Hz), 132.3, 126.9 (q, J = 3.5 Hz), 126.25, 124.2, 121.3, 119.9 (q, J = 272.3 Hz), 31.5, 28.8, 27.8, 25.5, 22.5, 20.9, 14.0. HRMS (ESI) m / z: calculated value C 18 H 21 F3O4Na[M+Na] + 381.1284, measured value: 381.1279.

[0041] I-2: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ8.15(d,J=7.9Hz,1H,ArH),7.69-7.63(m,1H,ArH),7.41-7.35(m,1H,ArH),7.20(d,J=8.1Hz,1H,ArH),6.17(t,J=7. 6Hz,1H,C=CH),2.35(s,3H,COCH3),2.10-2.01(m,2H,CH2),1.47-1.38(m,2H,CH2),1.30-1.24(m,8H,(CH2)4),0.87(t,J=6.6Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) δ 169.4, 160.8, 151.4, 135.0, 134.5 (q, J = 36.4 Hz), 132.3, 126.9 (q, J = 3.3 Hz), 126.2, 124.1, 121.4, 119.9 (q, J = 272.2 Hz), 31.7, 29.1, 28.9, 27.9, 25.4, 22.6, 20.8, 14.0. HRMS (ESI) m / z: calculated value C 19 H 23 F3O4Na[M+Na] + 395.1440, measured value: 395.1438.

[0042] I-3: light yellow liquid, 1H NMR (400MHz, CDCl3), δ8.15(d,J=7.9Hz,1H,ArH),7.69-7.62(m,1H,ArH),7.41-7.35(m,1H,ArH),7.20(d,J=8.1Hz,1H,ArH),6.19(t,J=7. 6Hz,1H,C=CH),2.35(s,3H,COCH3),2.09-2.01(m,2H,CH2),1.48-1.38(m,2H,CH2),1.34-1.24(m,10H,(CH2)5),0.89(t,J=6.5Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) (missing one carbon signal) δ 169.4, 160.8, 151.4, 135.0, 134.5 (q, J = 36.3 Hz), 132.2, 126.9 (q, J = 3.5 Hz), 126.2, 124.1, 121.4, 119.9 (q, J = 272.3 Hz), 31.8, 29.3, 29.1, 27.9, 25.4, 22.6, 20.8, 14.0. HRMS (ESI) m / z: calculated value C 20 H 25 F3O4Na[M+Na] + 409.1597, measured value: 409.1604.

[0043] I-4: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ8.13(d,J=7.9Hz,1H,ArH),7.69-7.62(m,1H,ArH),7.41-7.34(m,1H,ArH),7.17(d,J=8.2Hz,1H,ArH),6.17(t,J=7. 6Hz,1H,C=CH),2.32(s,3H,COCH3),2.10-2.01(m,2H,CH2),1.48-1.38(m,2H,CH2),1.33-1.20(m,14H,(CH2)7),0.88(t,J=6.6Hz,3H,CH3). 13C NMR (101 MHz, CDCl3) δ 169.4, 160.9, 151.4, 135.1, 134.5 (q, J = 36.5 Hz), 132.3, 126.9 (q, J = 3.4 Hz), 126.2, 124.2, 121.4, 119.9 (q, J = 272.3 Hz), 31.9, 29.6, 29.5, 29.32, 29.31, 29.1, 27.9, 25.5, 22.7, 20.9, 14.1. HRMS (ESI) m / z: calculated value C 22 H 29 F3O4Na[M+Na] + 437.1910, measured value: 437.1894.

[0044] I-5: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ8.13(d,J=7.9Hz,1H,ArH),7.69-7.62(m,1H,ArH),7.41-7.35(m,1H,ArH),7.17(d,J=8.1Hz,1H,ArH),6.17(t,J=7. 6Hz,1H,C=CH),2.33(s,3H,COCH3),2.09-2.01(m,2H,CH2),1.48-1.38(m,2H,CH2),1.29-1.22(m,18H,(CH2)9),0.88(t,J=6.6Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) δ 168.4, 159.8, 150.4, 134.0, 133.5 (q, J = 36.4 Hz), 131.2, 125.9 (q, J = 3.5 Hz), 125.2, 123.1, 120.4, 118.9 (q, J = 272.4 Hz), 30.9, 28.63, 28.61, 28.59, 28.5, 28.32, 28.30, 28.1, 26.9, 24.4, 21.7, 19.8, 13.1. HRMS (ESI) m / z: calculated value C 24 H 33 F3O4Na[M+Na] + 465.2223, measured value: 465.2208.

[0045] I-6: light yellow liquid, 1H NMR (400MHz, CDCl3), δ8.13(d,J=7.9Hz,1H),7.68-7.62(m,1H,ArH),7.40-7.34(m,1H,ArH),7.17(d,J=8.2Hz,1H,ArH ),6.17(t,J=7.6Hz,1H),2.32(s,3H,COCH3),2.10-2.02(m,2H,CH2),1.46-1.39(m,2H,CH2),1.30-1.23(m,22H,(CH2) 11 ), 0.88 (t, J = 6.8 Hz, 3H, CH3). 13 C NMR (101 MHz, CDCl3) δ 169.4, 160.9, 151.4, 135.1, 134.4 (q, J = 36.4 Hz), 132.3, 126.9 (q, J = 3.4 Hz), 126.2, 124.2, 121.3, 119.9 (q, J = 272.2 Hz), 31.9, 30.9, 29.70, 29.68, 29.66, 29.6, 29.5, 29.4, 29.3, 29.2, 27.9, 25.4, 22.7, 20.9, 14.1. HRMS (ESI) m / z: calculated value C 26 H 37 F3O4Na[M+Na] + 493.2536, measured value: 493.2513.

[0046] I-7: light yellow liquid, 1 H NMR(400MHz, CDCl3), δ8.12(dd,J=7.9,1.7Hz,1H,ArH),7.68-7.62(m,1H,ArH),7.41-7.34(m,1H,ArH),7.17(dd,J=8.1,1.1Hz,1 H,ArH),6.17(t,J=7.5Hz,1H,C=CH),2.32(s,3H,COCH3),2.10-2.00(m,2H,CH2),1.46-1.39(m,2H,CH2),1.30-1.23(m,26H,(CH2) 13 ), 0.88 (t, J = 6.6 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) 13C NMR (101 MHz, CDCl3) (missing three carbon signals) δ 169.4, 159.8, 151.4, 135.1, 134.4 (q, J = 36.5 Hz), 132.3, 126.9, 126.2, 124.2, 121.4, 119.9 (q, J = 273.1 Hz), 31.9, 29.71, 29.69, 29.673, 29.665, 29.6, 29.5, 29.4, 29.3, 29.1, 25.5, 22.7, 20.9, 14.1. HRMS (ESI) m / z: calculated value C 28 H 41 F3O4Na[M+Na] + 521.2849, measured value: 521.2856.

[0047] I-8: light yellow liquid, 1 H NMR(400MHz, CDCl3), δ8.13(dd,J=7.9,1.7Hz,1H,ArH),7.69-7.61(m,1H,ArH),7.41-7.34(m,1H,ArH),7.17(dd,J=8.1,1.2Hz,1 H,ArH),6.17(t,J=7.5Hz,1H,C=CH),2.32(s,3H,COCH3),2.09-2.02(m,2H,CH2),1.47-1.40(m,2H,CH2),1.28-1.24(m,30H,(CH2) 15 ), 0.88 (t, J = 6.8 Hz, 3H, CH3). 13 C NMR (101 MHz, CDCl3) (missing three carbon signals) δ 169.5, 160.9, 151.4, 135.1, 134.4 (q, J = 36.4 Hz), 132.3, 126.9 (q, J = 3.4 Hz), 126.2, 124.2, 121.4, 119.9 (q, J = 272.2 Hz), 31.9, 29.71, 29.69, 29.68, 29.67, 29.6, 29.5, 29.4, 29.3, 29.1, 27.9, 25.5, 25.0, 22.7, 20.9, 14.1. HRMS (ESI) m / z: calculated value C 30 H 45 F3O4Na[M+Na] + 549.3162, measured value: 549.3167.

[0048] I-9: light yellow liquid, 1H NMR (400MHz, CDCl3), δ8.12(dd,J=7.9,1.7Hz,1H,ArH),7.68-7.62(m,1H,ArH),7.40-7.35(m,1H,ArH),7.17(dd,J=8.2,1.2Hz,1 H,ArH),6.17(t,J=7.6Hz,1H,C=CH),2.32(s,3H,COCH3),2.10-2.02(m,2H,CH2),1.47-1.39(m,2H,CH2),1.34-1.20(m,34H,(CH2) 17 ), 0.88 (t, J = 6.6 Hz, 3H, CH3). 13 C NMR (101 MHz, CDCl3) (missing seven carbon signals) δ 169.5, 160.9, 151.4, 135.1, 134.4 (q, J = 36.3 Hz), 132.3, 126.9 (q, J = 3.6 Hz), 126.2, 124.2, 121.4, 119.9 (q, J = 272.6 Hz), 31.9, 29.7, 29.7, 29.7, 29.6, 29.5, 29.4, 29.3, 29.2, 27.9, 25.5, 22.7, 20.9, 14.1. HRMS (ESI) m / z: calculated value C 32 H 49 F3O4Na[M+Na] + 577.3475, measured value: 577.3448.

[0049] I-10: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ8.13(d,J=7.9Hz,1H,ArH),7.69-7.62(m,1H,ArH),7.41-7.33(m,1H,ArH),7.17(d,J=8.1Hz,1H,ArH),6.17(t,J=7. 6Hz,1H,C=CH),5.41-5.29(m,2H,CH=CH),2.33(s,3H,COCH3),2.06-1.98(m,4H,(CH2)2),1.48-1.39(m,2H,CH2),1.31-1.22(m,20H,(CH2) 10 ), 0.88 (t, J = 6.6 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 168.4, 159.8, 150.3, 134.0, 131.2, 129.1, 128.6, 125.8 (q, J = 3.1 Hz), 125.2, 125.1, 123.1, 123.0, 120.3, 118.9 (q, J = 273.7 Hz), 30.9, 28.7, 28.6, 28.5, 28.3, 28.1, 28.0, 27.9, 26.8, 26.2, 26.1, 24.4, 21.7, 19.8, 13.1. HRMS (ESI) m / z: calculated value C 28 H 39 F3O4Na[M+Na] + 519.2692, measured value: 519.2667.

[0050] I-11: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ8.13 (dd, J=7.9, 1.7Hz, 1H, ArH), 7.68-7.60 (m, 1H, ArH), 7.42 -7.33(m,1H,ArH),7.17(dd,J=8.2,1.2Hz,1H,ArH),6.16(t,J=7.5Hz,1H,C=CH),5.43 -5.26(m,4H,(CH=CH)2),2.80-2.72(m,2H,CH2),2.32(s,3H,COCH3),2.04(m,6H,(CH 2)3),1.47-1.40(m,2H,CH2),1.35-1.26(m,12H,(CH2)6),0.88(t,J=6.6Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) δ 169.4, 160.8, 151.4, 135.1, 134.5 (q, J = 36.4 Hz), 132.3, 130.3, 129.9, 128.1, 127.9, 126.8, 126.2 (q, J = 3.1 Hz), 124.2, 121.3, 119.9 (q, J = 273.2 Hz), 31.5, 29.5, 29.4, 29.1, 29.0, 27.9, 27.2, 27.2, 25.6, 25.4, 22.6, 20.9, 14.1. HRMS (ESI) m / z: calculated value C 28 H 37 F3O4Na[M+Na] + 517.2536, measured value: 517.2519.

[0051] I-12: light yellow liquid, 1H NMR(400MHz, CDCl3), δ8.13(dd,J=7.9,1.7Hz,1H,ArH),7.71-7.64(m,1H,ArH),7.43-7.37( m,1H,ArH),7.17(dd,J=8.2,1.2Hz,1H,ArH),6.17(t,J=7.6Hz,1H,C=CH),5.49-5.27(m,8H,( CH=CH)4),2.88-2.78(m,6H,(CH2)3),2.32(s,3H,COCH3),2.26-2.18(m,2H,CH2),2.18-2.1 0(m,2H,CH2),2.09-2.01(m,2H,CH2),1.42-1.18(m,6H,(CH2)3),0.87(t,J=6.6Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) (missing one carbon signal) δ 169.5, 160.8, 151.4, 135.1, 134.8 (q, J = 36.5 Hz), 132.3, 130.5, 129.6, 128.6, 128.4, 127.9, 127.9, 127.8, 127.5, 126.3, 126.0 (q, J = 3.4 Hz), 124.2, 121.2, 119.8 (q, J = 272.2 Hz), 31.5, 29.3, 27.2, 25.64, 25.62, 25.5, 25.4, 22.6, 20.9, 14.1. HRMS (ESI) m / z: calculated value C 30 H 37 F3O4Na[M+Na] + 541.2536, measured value: 541.2512.

[0052] I-13: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ8.15(d,J=7.8Hz,1H,ArH),7.69-7.62(m,1H,ArH),7.40-7.35(m,1H,ArH),7.20(d,J=8.1Hz,1H,ArH),6.19(t,J=7. 6Hz,1H,C=CH),5.42-5.34(m,2H,CH=CH),2.35(s,3H,COCH3),2.10-1.95(m,6H,(CH2)3),1.47-1.38(m,2H,CH2),1.32-1.23(m,26H,(CH2) 13 ), 0.90 (t, J = 6.6 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) (missing two carbon signals) δ 169.4, 160.8, 151.4, 135.0, 134.5 (q, J = 36.3 Hz), 132.3, 129.92, 129.86, 126.9, 126.2 (q, J = 3.4 Hz), 124.2, 121.4, 119.9 (q, J = 272.1 Hz), 32.6, 31.9, 29.8, 29.69, 29.66, 29.60, 29.57, 29.52, 29.47, 29.3, 29.1, 27.9, 27.2, 25.4, 22.7, 20.8, 14.1. HRMS (ESI) m / z: calculated value C 32 H 47 F3O4Na[M+Na] + 575.3318, measured value: 575.3310.

[0053] I-14: light yellow liquid, 1 H NMR(400MHz, CDCl3), δ7.25(d,J=7.9Hz,2H,(ArH)2),7.12(d,J=7.9Hz,2H,(ArH) 2),5.97(t,J=7.6Hz,1H,C=CH),3.88(q,J=7.1Hz,1H,COCH),2.46(d,J=7.2Hz,2H ,CH2),1.90-1.79(m,1H,CH),1.72-1.61(m,2H,CH2),1.57(d,J=7.1Hz,3H,CH3), 1.33-1.22(m,2H,CH2),0.89(d,J=6.6Hz,6H,(CH3)2),0.75(t,J=7.3Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) 171.3, 141.1, 136.5, 135.0 (q, J = 36.2 Hz), 129.5, 127.3, 125.9 (q, J = 3.6 Hz), 119.8 (q, J = 272.3 Hz), 45.0, 44.7, 30.2, 26.9, 22.31, 22.30, 21.1, 17.9, 13.5. HRMS (ESI) m / z: calculated for C 19 H 25 F3O2Na[M+Na] + 365.1699, measured value: 365.1690.

[0054] I-15: light yellow liquid, 1H NMR (400MHz, CDCl3), δ7.25(d,J=7.7Hz,2H,(ArH)2),7.12(d,J=7.7Hz,2H,(ArH)2 ),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H,COCH),2.45(d,J=7.2Hz,2H,C H2),1.89-1.79(m,1H,CH),1.75-1.65(m,2H,CH2),1.57(d,J=7.1Hz,3H,CH3),1.3 0-1.09(m,4H,(CH2)2),0.89(d,J=6.6Hz,6H,(CH3)2),0.79(t,J=7.1Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) 171.3, 141.1, 136.4, 134.8 (q, J = 36.2 Hz), 129.5, 127.3, 126.1 (q, J = 3.5 Hz), 119.9 (q, J = 272.4 Hz), 45.0, 44.7, 30.2, 29.8, 24.6, 22.32, 22.3022.1, 17.9, 13.6. HRMS (ESI) m / z: calculated value C 20 H 27 F3O2Na[M+Na] + 379.1855, measured value: 379.1853.

[0055] I-16: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.25(d,J=7.9Hz,2H,(ArH)2),7.12(d,J=7.9Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H,COCH),2.45( d,J=7.2Hz,2H,CH2),1.91-1.80(m,1H,CH),1.72-1.63(m,2H,CH2),1.5(d ,J=7.1Hz,3H,CH3),1.24-1.09(m,8H,(CH2)4),0.91-0.86(m,9H,(CH3)3). 13C NMR (101 MHz, CDCl3) 171.3, 141.1, 136.5, 134.7 (q, J = 36.3 Hz), 129.5, 127.3, 126.1 (q, J = 3.3 Hz), 119.9 (q, J = 272.3 Hz), 45.0, 44.7, 31.4, 30.2, 28.7, 27.7, 25.0, 22.5, 22.33, 22.31, 17.9, 14.0. HRMS (ESI) m / z: calcd. 22 H 31 F3O2Na[M+Na] + 407.2168, measured value: 407.2160.

[0056] I-17: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.24(d,J=7.8Hz,2H,(ArH)2),7.12(d,J=7.8Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H,COCH),2.46(d ,J=7.1Hz,2H,CH2),1.91-1.78(m,1H,CH),1.74-1.62(m,2H,CH2),1.57(d, J=7.1Hz,3H,CH3),1.30-1.09(m,10H,(CH2)5),0.92-0.84(m,9H,(CH3)3). 13 C NMR (101 MHz, CDCl3) 171.3, 141.1, 136.5, 134.8 (q, J = 36.2 Hz), 129.5, 127.3, 126.1 (q, J = 3.5 Hz), 119.9 (q, J = 272.3 Hz), 45.0, 44.7, 31.7, 30.2, 29.1, 28.9, 27.7, 25.0, 22.6, 22.33, 22.31, 17.9, 14.1. HRMS (ESI) m / z: calculated for C 23 H 33 F3O2Na[M+Na] + 421.2345, measured value: 421.2325.

[0057] I-18: light yellow liquid, 1H NMR (400MHz, CDCl3), δ7.24(d,J=8.0Hz,2H,(ArH)2),7.13(d,J=8.0Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H,COCH),2.46(d ,J=7.2Hz,2H,CH2),1.90-1.79(m,1H,CH),1.74-1.63(m,2H,CH2),1.57(d, J=7.1Hz,3H,CH3),1.33-1.11(m,12H,(CH2)6),0.91-0.85(m,9H,(CH3)3). 13 C NMR (101 MHz, CDCl3) 171.3, 141.1, 136.5, 134.8 (q, J = 36.2 Hz), 129.5, 127.3, 126.1 (q, J = 3.3 Hz), 119.9 (q, J = 272.3 Hz), 45.0, 44.8, 31.8, 30.2, 29.21, 29.18, 29.1, 27.8, 25.0, 22.7, 22.34, 22.32, 17.9, 14.1. HRMS (ESI) m / z: calculated for C 24 H 35 F3O2Na[M+Na] + 435.2481, measured value: 435.2471.

[0058] I-19: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.24(d,J=7.8Hz,2H,(ArH)2),7.11(d,J=7.7Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H,COCH),2.46(d ,J=7.1Hz,2H,CH2),1.91-1.78(m,1H,CH),1.74-1.63(m,2H,CH2),1.57(d, J=7.1Hz,3H,CH3),1.34-1.06(m,16H,(CH2)8),0.92-0.86(m,9H,(CH3)3). 13C NMR (101 MHz, CDCl3) 171.3, 141.1, 136.5, 134.8 (q, J = 36.2 Hz), 129.5, 127.3, 126.1 (q, J = 3.4 Hz), 119.9 (q, J = 272.2 Hz), 45.0, 44.7, 31.9, 30.2, 29.6, 29.5, 29.4, 29.2, 29.1, 27.7, 25.0, 22.7, 22.33, 22.31, 17.9, 14.1. HRMS (ESI) m / z: calcd. 26 H 39 F3O2Na[M+Na] + 463.2794, measured value: 463.2794.

[0059] I-20: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.24(d,J=7.7Hz,2H,(ArH)2),7.11(d,J=7.7Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H ,COCH),2.46(d,J=7.1Hz,2H,CH2),1.90-1.79(m,1H,CH),1.72-1.62(m,2H,CH2),1.57(d,J=7.1Hz,3H,CH3),1.30-1.11(m,20H,(CH2) 10 ),0.91-0.86(m,9H,(CH3)3). 13 C NMR (101 MHz, CDCl3) 171.3, 141.1, 136.5, 134.8 (q, J = 36.3 Hz), 129.5, 127.3, 126.1 (q, J = 3.4 Hz), 119.9 (q, J = 272.3 Hz), 45.0, 44.7, 31.9, 30.2, 29.71, 29.70, 29.6, 29.5, 29.4, 29.2, 29.1, 27.8, 25.0, 22.7, 22.34, 22.32, 17.9, 14.1. HRMS (ESI) m / z: calcd. 28 H 43 F3O2Na[M+Na] + 491.3107, measured value: 491.3101.

[0060] I-21: light yellow liquid, 1H NMR (400MHz, CDCl3), δ7.24(d,J=8.1Hz,2H,(ArH)2),7.11(d,J=8.1Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H ,COCH),2.45(d,J=7.2Hz,2H,CH2),1.88-1.81(m,1H,CH),1.70-1.64(m,2H,CH2),1.57(d,J=7.1Hz,3H,CH3),1.32-1.16(m,22H,(CH2) 11 ),0.91-0.86(m,9H,(CH3)3). 13 C NMR (101 MHz, CDCl3) δ 171.3, 141.1, 136.5, 134.8 (q, J = 36.3 Hz), 129.5, 127.3, 126.1 (q, J = 3.5 Hz), 119.9 (q, J = 272.2 Hz), 45.0, 44.7, 31.9, 30.2, 29.71, 29.70, 29.68, 29.63, 29.5, 29.4, 29.2, 29.1, 27.8, 25.0, 22.7, 22.34, 22.32, 17.9, 14.1. HRMS (ESI) m / z: calculated value C 29 H 45 F3O2Na[M+Na] + 505.3264, measured value: 505.3250.

[0061] I-22: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.25(d,J=7.7Hz,2H,(ArH)2),7.11(d,J=7.7Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H ,COCH),2.46(d,J=7.2Hz,2H,CH2),1.90-1.79(m,1H,CH),1.72-1.63(m,2H,CH2),1.57(d,J=7.1Hz,3H,CH3),1.30-1.19(m,24H,(CH2) 12 ),0.91-0.86(m,9H,(CH3)3). 13C NMR (101 MHz, CDCl3) δ 171.3, 141.1, 136.5, 134.8 (q, J = 36.2 Hz), 129.5, 127.3, 126.2 (q, J = 3.3 Hz), 119.9 (q, J = 272.3 Hz), 60.6, 45.0, 44.7, 31.9, 30.2, 29.73, 29.71, 29.68, 29.6, 29.5, 29.4, 29.2, 29.1, 27.8, 25.0, 22.7, 22.33, 22.32, 17.9, 14.1. HRMS (ESI) m / z: calculated value C 30 H 47 F3O2Na[M+Na] + 519.3420, measured value: 519.3408.

[0062] I-23: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.24(d,J=7.7Hz,2H,(ArH)2),7.12(d,J=7.7Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.88(q,J=7.1Hz,1H ,COCH),2.46(d,J=7.2Hz,2H,CH2),1.92-1.80(m,1H,CH),1.76-1.64(m,2H,CH2),1.57(d,J=7.1Hz,3H,CH3),1.32-1.14(m,26H,(CH2) 13 ),0.93-0.85(m,9H,(CH3)3). 13 C NMR (101 MHz, CDCl3) δ 171.3, 141.1, 136.5, 134.8 (q, J = 36.3 Hz), 129.5, 127.3, 126.1 (q, J = 3.4 Hz), 119.9 (q, J = 272.4 Hz), 45.0, 44.7, 31.9, 30.2, 29.73, 29.72, 29.71, 29.68, 29.6, 29.5, 29.4, 29.2, 29.1, 27.8, 25.0, 22.7, 22.34, 22.32, 17.9, 14.1. HRMS (ESI) m / z: calculated value C 31 H 49 F3O2Na[M+Na] + 533.3577, measured value: 533.3562.

[0063] I-24: light yellow liquid, 1H NMR (400MHz, CDCl3), δ7.25(d,J=8.0Hz,2H,(ArH)2),7.11(d,J=8.0Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H ,COCH),2.46(d,J=7.3Hz,2H,CH2),1.89-1.79(m,1H,CH),1.71-1.64(m,1H,CH),1.57(d,J=7.1Hz,3H,CH3),1.29-1.20(m,28H,(CH2) 14 ),0.90-0.85(m,9H,(CH3)3). 13 C NMR (101 MHz, CDCl3) (missing four carbon signals) δ 171.3, 141.1, 136.5, 134.8 (q, J = 36.3 Hz), 129.5, 127.3, 126.1 (q, J = 3.4 Hz), 119.9 (q, J = 272.3 Hz), 45.0, 44.7, 31.9, 30.2, 29.73, 29.68, 29.6, 29.5, 29.4, 29.2, 29.1, 27.8, 25.0, 22.7, 22.34, 22.32, 17.9, 14.1. HRMS (ESI) m / z: calculated value C 32 H 51 F3O2Na[M+Na] + 547.3733, measured value: 547.3717.

[0064] I-25: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.24(d,J=8.1Hz,2H,(ArH)2),7.11(d,J=8.1Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H ,COCH),2.46(d,J=7.2Hz,2H,CH2),1.90-1.79(m,1H,CH),1.73-1.64(m,2H,CH2),1.57(d,J=7.1Hz,3H,CH3),1.31-1.17(m,30H,(CH2) 15 ),0.92-0.86(m,9H,(CH3)3). 13C NMR (101 MHz, CDCl3) (missing five carbon signals) δ 171.3, 141.1, 136.5, 134.8 (q, J = 36.2 Hz), 129.5, 127.3, 126.1 (q, J = 3.6 Hz), 119.9 (q, J = 272.1 Hz), 45.0, 44.7, 31.9, 30.2, 29.73, 29.68, 29.6, 29.5, 29.4, 29.2, 29.1, 27.8, 25.0, 22.7, 22.34, 22.32, 17.9, 14.1. HRMS (ESI) m / z: calculated value C 33 H 53 F3O2Na[M+Na] + 561.3890, measured value: 561.3867.

[0065] I-26: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.24(d,J=8.1Hz,2H,(ArH)2),7.12(d,J=8.1Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H ,COCH),2.46(d,J=7.2Hz,2H,CH2),1.90-1.79(m,1H,CH),1.74-1.63(m,2H,CH2),1.57(d,J=7.1Hz,3H,CH3),1.31-1.14(m,32H,(CH2) 16 ),0.91-0.86(m,9H,(CH3)3). 13 C NMR (101 MHz, CDCl3) (missing six carbon signals) δ 171.3, 141.1, 136.5, 134.8 (q, J = 36.2 Hz), 129.5, 127.3, 126.1 (q, J = 3.5 Hz), 119.9 (q, J = 272.3 Hz), 45.0, 44.7, 32.0, 30.2, 29.73, 29.69, 29.6, 29.5, 29.4, 29.2, 29.1, 27.8, 25.0, 22.7, 22.34, 22.32, 17.9, 14.1. HRMS (ESI) m / z: calculated value C 34 H 55 F3O2Na[M+Na] + 543.3420, measured value: 543.3409.

[0066] I-27: light yellow liquid, 1H NMR (400MHz, CDCl3), δ7.25(d,J=8.1Hz,2H,(ArH)2),7.12(d,J=8.1Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),3.87(q,J=7.1Hz,1H ,COCH),2.46(d,J=7.2Hz,2H,CH2),1.90-1.79(m,1H,CH),1.72-1.64(m,2H,CH2),1.57(d,J=7.1Hz,3H,CH3),1.29-1.13(m,36H,(CH2) 18 ),0.91-0.86(m,9H,(CH3)3). 13 C NMR (101 MHz, CDCl3) (missing eight carbon signals) δ 171.3, 141.1, 136.5, 134.8 (q, J = 36.0 Hz), 129.5, 126.1 (q, J = 3.4 Hz), 119.9 (q, J = 272.3 Hz), 45.0, 44.7, 31.9, 30.2, 29.73, 29.68, 29.6, 29.5, 29.4, 29.2, 29.1, 27.8, 25.0, 22.7, 22.34, 22.32, 17.9, 14.1. HRMS (ESI) m / z: calculated value C 36 H 59 F3O2Na[M+Na] + 603.4359, measured value: 603.4338.

[0067] I-28: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.24(d,J=8.0Hz,2H,(ArH)2),7.11(d,J=8.0Hz,2H,(ArH)2),5.97(t,J=7.6Hz,1H,C=CH),5.36(m,2H,CH=CH),3.87(q,J =7.1Hz,1H,COCH),2.45(d,J=7.2Hz,2H,CH2),2.05-1.96(m,2H,CH2),1.90-1.78(m,1H,CH),1.56(d,J=7.1Hz,3H,CH3)1.39-1.05(m,22H,(CH2) 11 ),0.91-0.86(m,9H,(CH3)3). 13C NMR (101 MHz, CDCl3) δ 171.3, 141.1, 136.5, 134.8 (q, J = 36.3 Hz), 130.1, 129.6, 129.5, 126.1 (q, J = 3.9 Hz), 127.3, 119.9 (q, J = 271.9 Hz), 45.0, 44.7, 31.9, 30.2, 29.8, 29.7, 29.6, 29.5, 29.39, 29.36, 29.2, 28.9, 27.8, 27.2, 25.0, 22.7, 22.34, 22.32, 17.9, 14.1. HRMS (ESI) m / z: calculated value C 32 H 49 F3O2Na[M+Na] + 545.3577, measured value: 545.3565.

[0068] I-29: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.24(d,J=8.1Hz,2H,(ArH)2),7.11(d,J=8.1Hz,2H,(ArH)2),5.96(t,J= 7.6Hz,1H,C=CH),5.43-5.31(m,4H,(CH=CH)2),3.87(q,J=7.1Hz,1H,COCH),2.77(t,J=6.1Hz,2 H,CH2),2.45(d,J=7.2Hz,2H,CH2),2.08-2.00(m,4H,(CH2)2),1.89-1.80(m,1H,CH),1.74-1.6 3(m,2H,CH2),1.57(d,J=7.1Hz,3H,CH3),1.41-1.08(m,16H,(CH2)8)0.90-0.87(m,9H,(CH3)3). 13 C NMR (101 MHz, CDCl3) δ 171.3, 141.1, 136.5, 134.8 (q, J = 36.2 Hz), 130.3, 129.9, 129.5, 128.2, 127.9, 127.3, 126.1 (q, J = 3.4 Hz), 119.9 (q, J = 272.4 Hz), 45.0, 44.7, 31.5, 30.2, 29.5, 29.4, 29.0, 28.9, 27.7, 27.2, 27.2, 25.6, 25.0, 22.6, 22.33, 22.31, 17.9, 14.1. HRMS (ESI) m / z: calculated value C 32 H 47 F3O2Na[M+Na] +543.3420, measured value: 543.3409.

[0069] I-30: light yellow liquid, 1 H NMR(400MHz, CDCl3), δ7.24(d,J=8.1Hz,2H,(ArH)2),7.11(d,J=8.1Hz,2H,(ArH)2),5.9 8(t,J=7.6Hz,1H,C=CH),5.36-5.17(m,8H,(CH=CH)4),2.87-2.72(m,6H,(CH2)3),2.46( d,J=7.2Hz,2H,CH2),2.10-2.00(m,4H,(CH2)2),1.90-1.82(m,1H,CH),1.81-1.72(m,2H ,CH2),1.57(d,J=7.2Hz,3H,CH3),1.38-1.25(m,6H,(CH2)3),0.91-0.86(m,9H,(CH3)3). 13 C NMR (101 MHz, CDCl3) δ 171.3, 141.1, 136.4, 135.1 (q, J = 36.3 Hz), 130.5, 129.5, 129.4, 128.6, 128.4, 127.90, 127.88, 127.8, 127.5, 127.3, 125.2 (q, J = 3.3 Hz), 119.9 (q, J = 272.4 Hz), 45.0, 44.8, 31.5, 30.2, 29.4, 27.2, 25.7, 25.64, 25.58, 25.4, 24.9, 22.6, 22.34, 22.32, 18.0, 14.1. HRMS (ESI) m / z: calculated value C 34 H 47 F3O2Na[M+Na] + 567.3420, measured value: 567.3399.

[0070] I-31: light yellow liquid, 1H NMR (400MHz, CDCl3), δ7.24(d,J=7.9Hz,2H,(ArH)2),7.11(d,J=7.9Hz,2H,(ArH) )2),5.97(t,J=7.6Hz,1H,C=CH),5.40-5.28(m,2H,CH=CH),3.87(q,J=7.1Hz,1H, COCH),2.45(d,J=7.2Hz,2H,CH2),2.06-1.95(m,4H,(CH2)2),1.89-1.79(m,1H, CH),1.72-1.63(m,2H,CH2),1.57(d,J=7.1Hz,3H,CH3),1.35-1.18(m,28H,(CH2) 14 ),0.91-0.86(m,9H,(CH3)3). 13 C NMR (101 MHz, CDCl3) δ 171.3, 141.1, 136.5, 134.6 (q, J = 36.2 Hz), 130.0, 129.9, 129.5, 127.3, 126.1 (q, J = 3.4 Hz), 119.9 (q, J = 272.2 Hz), 45.0, 44.7, 31.9, 30.2, 29.81, 29.79, 29.73, 29.68, 29.61, 29.59, 29.55, 29.51, 29.34, 29.25, 29.1, 27.8, 27.2, 25.0, 22.7, 22.4, 22.3, 17.9, 14.1. HRMS (ESI) m / z: calculated for C 36 H 57 F3O2Na[M+Na] + 601.4203, measured value: 601.4194.

[0071] I-32: light yellow liquid, 1H NMR(400MHz, CDCl3), δ7.74-7.69(m,3H,(ArH)3),7.43(dd,J=8.6,1.8Hz,1H,ArH),7.15 (dd,J=8.9,2.6Hz,1H,ArH),7.12(d,J=2.6Hz,1H,ArH),5.97(t,J=7.6Hz,1H,C=CH),4.0 4(q,J=7.1Hz,1H,COCH),3.92(s,3H,OCH3),1.66(d,J=7.1Hz,3H,CH3),1.24-1.14(m,4H ,(CH2)2),1.12-1.01(m,4H,(CH2)2),1.00-0.91(m,2H,CH2),0.85(t,J=7.2Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) δ 171.3, 157.9, 134.8 (q, J = 36.2 Hz), 134.3, 134.0, 129.3, 128.9, 127.4, 126.3, 126.2 (q, J = 3.4 Hz), 126.0, 119.9 (q, J = 272.2 Hz), 119.2, 105.6, 55.3, 45.1, 31.7, 29.0, 28.8, 27.7, 25.0, 22.6, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 24 H 29 F3O3Na[M+Na] + 445.1961, measured value: 445.1958.

[0072] I-33: light yellow liquid, 1 H NMR(400MHz, CDCl3), δ7.79-7.67(m,3H,(ArH)3),7.43(dd,J=8.6,1.8Hz,1H,ArH) ,7.15(dd,J=8.9,2.5Hz,1H,ArH),7.12(d,J=2.5Hz,1H,ArH),5.97(t,J=7.6Hz,1H, C=CH),4.04(q,J=7.1Hz,1H,COCH),3.92(s,3H,OCH3),1.66(d,J=7.1Hz,3H,CH3), 1.35-1.09(m,10H,(CH2)5),1.08-0.92(m,4H,(CH2)2),0.87(t,J=7.2Hz,3H,CH3). 13C NMR (101 MHz, CDCl3) δ 171.3, 157.9, 134.8 (q, J = 36.2 Hz), 134.3, 134.0, 129.3, 128.9, 127.4, 126.3, 126.2 (q, J = 3.4 Hz), 126.0, 119.9 (q, J = 272.3 Hz), 119.2, 105.6, 55.3, 45.1, 31.8, 29.1, 29.12, 29.05, 27.7, 25.0, 22.7, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 25 H 31 F3O3Na[M+Na] + 459.2117, measured value: 459.2113.

[0073] I-34: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.74-7.69(m,3H,(ArH)3),7.43(dd,J=8.6,1.8Hz,1H,ArH ),7.15(dd,J=8.9,2.6Hz,1H,ArH),7.12(d,J=2.6Hz,1H,ArH),5.97(t,J=7.6Hz,1 H,C=CH),4.04(q,J=7.1Hz,1H,COCH),3.92(s,3H,OCH3),1.66(d,J=7.1Hz,3H,CH3 ),1.34-1.00(m,16H,(CH2)8),0.99-0.92(m,2H,CH2),0.89(t,J=7.2Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) δ 171.3, 157.9, 134.8 (q, J = 36.2 Hz), 134.3, 134.0, 129.3, 129.0, 127.4, 126.3, 126.2 (q, J = 3.4 Hz), 126.0, 119.9 (q, J = 272.3 Hz), 119.2, 105.6, 55.3, 45.1, 31.9, 29.6, 29.5, 29.4, 29.15, 29.06, 27.7, 25.0, 22.7, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 27 H 35 F3O3Na[M+Na] + 487.2430, measured value: 487.2434.

[0074] I-35: light yellow liquid, 1H NMR (400MHz, CDCl3), δ7.74-7.69(m,3H,(ArH)3),7.43(dd,J=8.6,1.8Hz,1H,ArH),7.15(dd,J=8.9,2.5Hz,1H,ArH),7.12(d,J=2.6Hz,1 H,ArH),5.97(t,J=7.6Hz,1H,C=CH),4.04(q,J=7.1Hz,1H,COCH),3.92(s,3H,OCH3),1.66(d,J=7.1Hz,3H,CH3),1.35-1.00(m,20H,(CH2) 10 ),0.99-0.92(m,2H,CH2),0.89(t,J=7.2Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) δ 171.3, 157.9, 134.8 (q, J = 36.3 Hz), 134.3, 134.0, 129.3, 128.9, 127.4, 126.3, 126.2 (q, J = 3.5 Hz), 126.0, 119.9 (q, J = 272.2 Hz), 119.2, 105.6, 55.3, 45.1, 32.0, 29.69, 29.67, 29.6, 29.5, 29.4, 29.15, 29.06, 27.7, 25.0, 22.7, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 29 H 39 F3O3Na[M+Na] + 515.2743, measured value: 515.2741.

[0075] I-36: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.75-7.69(m,3H,(ArH)3),7.43(dd,J=8.5,1.8Hz,1H,ArH),7.15(dd,J=8.9,2.5Hz,1H,ArH),7.12(d,J=2.5Hz,1 H,ArH),5.97(t,J=7.6Hz,1H,C=CH),4.04(q,J=7.1Hz,1H,COCH),3.92(s,3H,OCH3),1.66(d,J=7.1Hz,3H,CH3),1.33-1.02(m,24H,(CH2) 12 ),1.00-0.93(m,2H,CH2),0.88(t,J=7.2Hz,3H,CH3). 13C NMR (101 MHz, CDCl3) (missing one carbon signal) δ 171.3, 157.9, 134.8 (q, J = 36.3 Hz), 134.3, 134.0, 129.3, 128.9, 127.4, 126.3, 126.2 (q, J = 3.5 Hz), 126.0, 119.9 (q, J = 272.2 Hz), 119.2, 105.6, 55.3, 45.1, 32.0, 29.8, 29.71, 29.70, 29.6, 29.5, 29.4, 29.2, 29.1, 27.7, 25.0, 22.7, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 31 H 43 F3O3Na[M+Na] + 543.3056, measured value: 543.3053.

[0076] I-37: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.74-7.68(m,3H,(ArH)3),7.43(dd,J=8.5,1.8Hz,1H,ArH),7.15(dd,J=8.9,2.6Hz,1H,ArH),7.12(d,J=2.6Hz,1 H,ArH),5.97(t,J=7.7Hz,1H,C=CH),4.04(q,J=7.1Hz,1H,COCH),3.92(s,3H,OCH3),1.66(d,J=7.2Hz,3H,CH3),1.34-1.01(m,28H,(CH2) 14 ),1.00-0.92(m,2H,CH2),0.87(t,J=7.2Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) (missing three carbon signals) δ 171.3, 157.9, 134.8 (q, J = 36.2 Hz), 134.3, 134.0, 129.3, 129.0, 127.4, 126.3, 126.2 (q, J = 3.5 Hz), 126.0, 119.9 (q, J = 272.2 Hz), 119.2, 105.6, 55.3, 45.1, 32.0, 29.8, 29.73, 29.71, 29.6, 29.5, 29.4, 29.2, 29.1, 27.7, 25.0, 22.7, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 33 H 47 F3O3Na[M+Na] + 571.3369, measured value: 571.3370.

[0077] I-38: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.74-7.69(m,3H,(ArH)3),7.43(dd,J=8.5,1.8Hz,1H,ArH),7.15(dd,J=8.9,2.6Hz,1H,ArH),7.12(d,J=2.6Hz,1H ,ArH),5.97(t,J=7.6,Hz,1H,C=CH),4.04(q,J=7.1Hz,1H,COCH),3.92(s,3H,OCH3),1.66(d,J=7.1Hz,3H,CH3),1.31-0.94(m,34H,(CH2) 17 ), 0.87 (t, J = 7.2 Hz, 3H, CH3). 13 C NMR (101 MHz, CDCl3) (missing six carbon signals) δ 171.3, 157.9, 134.8 (q, J = 36.2 Hz), 134.3, 134.0, 129.3, 129.0, 127.4, 126.3, 126.2 (q, J = 3.4 Hz), 126.0, 119.9 (q, J = 272.3 Hz), 119.2, 105.6, 55.3, 45.1, 32.0, 29.74, 29.70, 29.6, 29.5, 29.4, 29.2, 29.1, 27.7, 25.0, 22.7, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 35 H 51 F3O3Na[M+Na] + 599.3682, measured value: 599.3679.

[0078] I-39: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.75-7.68(m,3H,(ArH)3),7.43(dd,J=8.6,1.8Hz,1H,ArH),7.15(dd,J=8.9,2.6Hz,1H,ArH),7.12(d,J=2.6Hz,1 H,ArH),5.97(t,J=7.7Hz,1H,C=CH),4.04(q,J=7.1Hz,1H,COCH),3.92(s,3H,OCH3),1.66(d,J=7.1Hz,3H,CH3),1.34-1.00(m,36H,(CH2) 18 ),1.00-0.92(m,2H,CH2),0.87(t,J=7.2Hz,3H,CH3). 13C NMR (101 MHz, CDCl3) (missing seven carbon signals) δ 171.3, 157.9, 134.8 (q, J = 36.2 Hz), 134.3, 134.0, 129.3, 128.9, 127.4, 126.3, 126.2 (q, J = 3.3 Hz), 126.0, 119.9 (q, J = 272.3 Hz), 119.2, 105.6, 55.3, 45.1, 32.0, 29.74, 29.70, 29.69, 29.6, 29.5, 29.4, 29.2, 29.1, 27.7, 25.0, 22.7, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 37 H 55 F3O3Na[M+Na] + 627.4022, measured value: 627.3992.

[0079] I-40: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.75-7.68(m,3H,(ArH)3),7.43(dd,J=8.6,1.8Hz,1H,ArH ),7.15(dd,J=8.9,2.6Hz,1H,ArH),7.11(d,J=2.6Hz,1H,ArH),5.96(t,J=7.6Hz,1 H,C=CH),5.06-4.87(m,3H,CH=CH2),4.04(q,J=7.1Hz,1H,COCH),3.91(s,3H,OCH3 ),2.05-1.96(m,2H,CH2),1.66(d,J=7.1Hz,3H,CH3),1.33-0.91(m,12H,(CH2)6). 13 C NMR (101 MHz, CDCl3) δ 171.3, 157.9, 139.1, 134.8 (q, J = 36.2 Hz), 134.3, 134.0, 129.3, 128.9, 127.4, 126.3, 126.2 (q, J = 3.1 Hz), 126.0, 119.9 (q, J = 272.2 Hz), 119.2, 114.2, 105.6, 55.3, 45.1, 33.8, 28.98, 28.97, 28.9, 28.8, 27.7, 25.0, 18.1. HRMS (ESI) m / z: calculated value C 26 H 31 F3O3Na[M+Na] + 471.2117, measured value: 471.2112.

[0080] I-41: light yellow liquid,1 H NMR (400MHz, CDCl3), δ7.74-7.68(m,3H,(ArH)3),7.43(dd,J=8.5,1.8Hz,1H,A rH), 7.15 (dd, J=8.8, 2.6Hz, 1H, ArH), 7.11 (d, J=2.6Hz, 1H, ArH), 5.97 (t, J=7. 6Hz,1H,C=CH),5.34(m,2H,CH=CH),4.04(q,J=7.1Hz,1H,COCH),3.91(s,3H,OC H3),1.97(m,4H,(CH2)2),1.66(d,J=7.1Hz,3H,CH3),1.38-1.03(m,20H,(CH2) 10 ),1.00-0.93(m,2H,CH2),0.88(t,J=7.2Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) δ 171.3, 157.9, 134.8 (q, J = 36.2 Hz), 134.3, 134.0, 130.1, 129.7, 129.3, 128.9, 127.4, 126.3, 126.1 (q, J = 3.3 Hz), 126.0, 119.9 (q, J = 272.3 Hz), 119.2, 105.6, 55.3, 45.08, 31.9, 29.8, 29.7, 29.6, 29.4, 29.3, 29.0, 28.8, 27.7, 27.2, 27.1, 25.0, 22.7, 18.1, 14.1 HRMS (ESI) m / z: calculated value C 33 H 45 F3O3Na[M+Na] + 569.3213, measured value: 569.3200.

[0081] I-42: light yellow liquid, 1H NMR(400MHz, CDCl3), δ7.74-7.68(m,3H,(ArH)3),7.43(dd,J=8.6,1.8Hz,1H,ArH),7.15(dd,J=8.9,2.5Hz,1H,ArH),7.11 (d,J=2.5Hz,1H,ArH),5.96(t,J=7.6Hz,1H,C=CH),5.43-5.28(m,4H,(CH=CH)2),4.03(q,J=7.1Hz,1H,COCH),3.90(s,3H, OCH3),2.76(t,J=5.8Hz,2H,CH2),2.05(q,J=7.0Hz,2H,CH2),2.00-1.93(m,2H,CH2),1.66(d,J=7.1Hz,3H,CH3),1.38-1. 24(m,8H,(CH2)4),1.23-1.14(m,4H,(CH2)2),1.13-1.04(m,2H,CH2),1.01-0.93(m,2H,CH2),0.89(t,J=7.2Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) δ 171.3, 157.9, 134.8 (q, J = 36.2 Hz), 134.3, 134.0, 130.3, 130.0, 129.3, 128.9, 128.1, 127.9, 127.4, 126.3, 126.1 (q, J = 3.4 Hz), 126.0, 119.9 (q, J = 272.3 Hz), 119.2, 105.5, 55.3, 45.1, 31.6, 29.5, 29.4, 29.0, 28.8, 27.7, 27.2, 27.1, 25.6, 25.0, 22.6, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 33 H 43 F3O3Na[M+Na] + 567.3056, measured value: 567.3052.

[0082] I-43: light yellow liquid, 1H NMR (400MHz, CDCl3), δ7.74-7.69(m,3H,(ArH)3),7.42(dd,J=8.6,1.8Hz,1H,ArH),7.15(dd,J=8.9,2.6Hz,1H ,ArH),7.12(d,J=2.6Hz,1H,ArH),5.98(t,J=7.6Hz,1H,C=CH),5.40-5.07(m,8H,(CH=CH)4),4.04(q,J=7.1Hz ,1H,COCH),3.92(s,3H,OCH3),2.83-2.77(m,4H,(CH2)2),2.70(t,J=7.4Hz,2H,CH2),2.08-1.98(m,4H,(CH2) 2),1.83-1.72(m,2H,CH2),1.66(d,J=7.1Hz,3H,CH3),1.37-1.24(m,6H,(CH2)3),0.88(t,J=7.2Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) δ 171.2, 157.9, 135.1 (q, J = 36.0 Hz), 134.3, 134.0, 130.5, 129.34, 129.33, 128.9, 128.6, 128.3, 127.9, 127.82, 127.80, 127.5, 127.4, 126.3, 125.9, 125.33, 125.30, 119.2, 105.6, 55.3, 45.1, 31.5, 29.3, 27.2, 25.7, 25.6, 25.5, 25.3, 25.0, 22.6, 18.2, 14.1. HRMS (ESI) m / z: calcd. 35 H 43 F3O3Na[M+Na] + 591.3056, measured value: 591.3051.

[0083] I-44: light yellow liquid, 1H NMR (400MHz, CDCl3), δ7.74-7.69(m,3H,(ArH)3),7.43(dd,J=8.6,1.8Hz,1H,ArH ),7.15(dd,J=8.9,2.6Hz,1H,ArH),7.12(d,J=2.6Hz,1H,ArH),5.97(t,J=7.6Hz,1 H,C=CH),5.40-5.31(m,2H,CH=CH),4.04(q,J=7.1Hz,1H,COCH),3.92(s,3H,OCH3 ),2.08-1.97(m,4H,(CH2)2),1.66(d,J=7.1Hz,3H,CH3),1.38-1.02(m,28H,(CH2) 14 ),1.00-0.92(m,2H,CH2),0.88(t,J=7.2Hz,3H,CH3). 13 C NMR (101MHz, CDCl3) δ171.3, 157.9, 134.8 (q, J = 36.2Hz), 134.3, 134.0, 130.0, 129. 9,129.3,128.9,127.4,126.3,126.2(q,J=3.4Hz),126.0,119.9(q,J=272.3Hz),11 9.2,105.6,55.3,45.1,32.6,31.9,29.83,29.80,29.73,29.69,29.58,29.57,29.55,29.46,29.3,29.2,29.1,27.7,27.2,25.0,22.7,18.1,14.1. HRMS (ESI) m / z: calcd. 37 H 53 F3O3Na[M+Na] + 625.3839, measured value: 625.3825.

[0084] I-45: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.57-7.51(m,2H,(ArH)2),7.47-7.34(m,4H,(ArH)4),7.23-7.14(m,2H,(ArH)2),6.02(t,J=7.6Hz,1H,C=CH),3 .94(q,J=7.1Hz,1H,COCH),1.83-1.71(m,2H,CH2),1.62(d,J=7.1Hz,3H,CH3),1.32-1.14(m,10H,(CH2)5),0.84(t,J=6.9Hz,3H,CH3). 13C NMR (101MHz, CDCl3) δ170.6, 159.8 (d, J = 249.0Hz), 140.5 (d, J = 7.7Hz), 135.3 (d, J = 1.2 Hz), 134.7 (q, J = 36.4Hz), 131.0 (d, J = 4.0Hz), 129.0 (d, J = 2.9Hz), 128.5, 128.4 (d, J = 1 3.5Hz), 127.8, 126.4 (q, J = 3.5Hz), 123.6 (d, J = 3.4Hz), 119.8 (q, J = 272.2Hz), 115.4 (d, J = 23.9Hz), 44.6, 31.7, 29.1, 28.9, 27.8, 25.2, 22.6, 18.0, 14.1. HRMS (ESI) m / z: calculated value C 25 H 28 F4O2Na[M+Na] + 459.1917, measured value: 459.1902.

[0085] I-46: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.54(m,2H,(ArH)2),7.47-7.35(m,4H,(ArH)4),7.23-7.14(m,2H,(ArH)2),6.02(t,J=7.7Hz,1H,C=CH),3.9 4(q,J=7.1Hz,1H,COCH),1.84-1.72(m,2H,CH2),1.63(d,J=7.1Hz,3H,CH3),1.34-1.11(m,12H,(CH2)6),0.85(t,J=7.0Hz,3H,CH3). 13 C NMR (101MHz, CDCl3) δ170.6, 159.8 (d, J = 248.9Hz), 140.4 (d, J = 7.7Hz), 135.3 (d, J = 1.2H z),134.7(q,J=36.4Hz),131.0(d,J=4.0Hz),129.0(d,J=2.9Hz),128.4(d,J=13.6Hz),1 28.3,127.8,126.4 (q, J = 3.4 Hz),123.6 (d, J = 3.4 Hz),119.8 (q, J = 272.2 Hz),115.4 (d, J = 23.9 Hz),44.6,31.8,29.7,29.2,29.1,27.8,25.2,22.6,18.0,14.1. HRMS (ESI) m / z: calculated value C 26 H 30 F4O2Na[M+Na]+ 473.2074, measured value: 473.2064.

[0086] I-47: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.56-7.51(ArH)2),7.48-7.35(m,4H,(ArH)4),7.23-7.15(m,2H,(ArH)2),6.03(t,J=7.6Hz,1H,C=CH),3.95 (q,J=7.2Hz,1H,COCH),1.83-1.71(m,2H,CH2),1.63(d,J=7.2Hz,3H,CH3),1.32-1.14(m,16H,(CH2)8),0.88(t,J=7.0Hz,3H,CH3). 13 C NMR (101MHz, CDCl3) δ170.6, 159.8 (d, J = 249.0Hz), 140.4 (d, J = 7.7Hz), 135.3 (d, J = 1.2Hz), 134.7(q,J=36.3Hz),131.0(d,J=4.0Hz),129.0(d,J=2.9Hz),128.5,128.4(d,J=13.5Hz),1 27.8,126.4(q,J=3.4Hz),123.6(d,J=3.4Hz),119.8(q,J=272.4Hz),115.4(d,J=23.8Hz),44.6,31.9,29.6,29.5,29.3,29.24,29.19,27.8,25.2,22.7,18.0,14.1. HRMS(ESI) m / z: calcd. 28 H 34 F4O2Na[M+Na] + 501.2387, measured value: 501.2381.

[0087] I-48: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.58-7.51(m,2H,(ArH)2),7.48-7.34(m,4H,(ArH)4),7.23-7.14(m,2H,(ArH)2),6.03(t,J=7. 6Hz,1H,C=CH),3.95(q,J=7.1Hz,1H,COCH),1.84-1.70(m,2H,CH2),1.63(d,7.1Hz,3H,CH3),1.31-1.14(m,24H,(CH2) 12 ), 0.88 (t, J = 6.7 Hz, 3H, CH3).13 C NMR (101 MHz, CDCl3) (missing two carbon signals) δ 170.6, 159.8 (d, J = 249.0 Hz), 140.4 (d, J = 7.6 Hz), 135.3 (d, J = 1.2 Hz), 134.7 (q, J = 36.3 Hz), 131.0 (d, J = 3.9 Hz), 129.0 (d, J = 3.2 Hz), 128.4 (d, J = 13.5 Hz), 128.3, 127 .8,126.4(q,J=3.4Hz),123.6(d,J=3.3Hz),119.9(q,J=272.2Hz),115.4(d,J=23.9Hz),44.6,32.0,29.73,29.68,29.6,29.5,29.4,29.25,29.20,27.8,25.2,22.7,18.0,14.1. HRMS(ESI) m / z: calcd. 32 H 42 F4O2Na[M+Na] + 557.3013, measured value: 557.3004.

[0088] I-49: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.56-7.51(m,2H,(ArH)2),7.47-7.34(m,4H,(ArH)4),7.23-7.14(m,2H,(ArH)2),6.02(t,J=7.6 Hz,1H,C=CH),3.94(q,J=7.1Hz,1H,COCH),1.82-1.71(m,2H,CH2),1.62(d,J=7.1Hz,3H,CH3),1.31-1.15(m,28H,(CH2) 14 ), 0.88 (t, J = 6.7 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) (missing four carbon signals) δ 170.6, 159.8 (d, J = 249.0 Hz), 140.4 (d, J = 7.7 Hz), 135.3 (d, J = 1.2 Hz), 134.7 (q, J = 36.4 Hz), 131.0 (d, J = 4.0 Hz), 129.0 (d, J = 3.2 Hz), 128.4 (d, J = 13.5 Hz), 128.3, 127 .8,126.4(q,J=3.4Hz),123.6(d,J=3.4Hz),119.9(q,J=272.3Hz),115.4(d,J=23.9Hz),44.6,32.0,29.72,29.68,29.6,29.5,29.4,29.24,29.19,27.8,25.2,22.7,18.0,14.1. HRMS(ESI) m / z: calcd. 34 H 46 F4O2Na[M+Na] + 585.3326, measured value: 588.3303.

[0089] I-50: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.57-7.52(m,2H,(ArH)2),7.48-7.34(m,4H,(ArH)4),7.23-7.15(m,2H,(ArH)2),6.03(t,J=7.6 Hz,1H,C=CH),3.95(q,J=7.1Hz,1H,COCH),1.85-1.72(m,2H,CH2),1.63(d,J=7.1Hz,3H,CH3),1.31-1.18(m,32H,(CH2) 16 ), 0.89 (t, J = 6.7 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) (missing six carbon signals) δ 170.6, 159.8 (d, J = 249.0 Hz), 140.4 (d, J = 7.6 Hz), 135.3 (d, J = 1.2 Hz), 134.7 (q, J = 36.3 Hz), 131.0 (d, J = 4.0 Hz), 129.0 (d, J = 3.2 Hz), 128.4 (d, J = 13.5 Hz), 128.3, 1 27.8,126.4 (q, J = 3.4 Hz),123.6 (d, J = 3.4 Hz),119.9 (q, J = 272.3 Hz),115.4 (d, J = 23.9 Hz),44.6,32.0,29.8,29.7,29.6,29.5,29.4,29.3,29.2,27.8,25.2,22.7,18.0,14.1. HRMS (ESI) m / z: calculated value C 36 H 50 F4O2Na[M+Na] + 613.3639, measured value: 613.3637.

[0090] I-51: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.56-7.50(m,2H,(ArH)2),7.47-7.34(m,4H,(ArH)4),7.23-7.14(m,2H,(ArH)2),6.02(t,J=7.6 Hz,1H,C=CH),3.94(q,J=7.1Hz,1H,COCH),1.82-1.72(m,2H,CH2),1.62(d,J=7.2Hz,3H,CH3),1.30-1.14(m,36H,(CH2) 18 ), 0.88 (t, J = 6.8 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) (missing eight carbon signals) δ 170.6, 159.8 (d, J = 249.0 Hz), 140.4 (d, J = 7.6 Hz), 135.3 (d, J = 1.2 Hz), 134.7 (q, J = 36.3 Hz), 131.0 (d, J = 3.9 Hz), 129.0 (d, J = 3.2 Hz), 128.4 (d, J = 13.5 Hz), 128.3, 12 7.8,126.4(q,J=3.4Hz),123.6(d,J=3.4Hz),119.9(q,J=272.3Hz),115.4(d,J=23.9Hz),44.6,32.0,29.74,29.70,29.6,29.5,29.4,29.3,29.2,27.8,25.2,22.7,18.0,14.1. HRMS(ESI) m / z: calcd. 38 H 54 F4O2Na[M+Na] + 641.3952, measured value: 641.3953.

[0091] I-52: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.57-7.51(m,2H,(ArH)2),7.47-7.36(m,4H,(ArH)4),7.22- 7.14(m,2H,(ArH)2),6.02(t,J=7.3Hz,1H,C=CH),5.77(ddt,J=16.9,10.1,6.7Hz,1 H,CH=C),5.03-4.89(m,2H,C=CH2),3.95(q,J=7.2Hz,1H,COCH),2.06-1.95(m,2H,C H2),1.84-1.70(m,2H,CH2),1.63(d,J=7.2Hz,3H,CH3),1.33-1.14(m,10H,(CH2)5). 13C NMR (101MHz, CDCl3) δ170.6, 159.8 (d, J = 248.9Hz), 140.4 (d, J = 7.7Hz), 139.1, 135.3 (d, J = 1.2Hz), 134.7 (q, J = 36.3Hz), 131.0 (d, J = 3.9Hz), 128.9 (d, J = 2.9Hz), 128.4 (d, J = 13.5Hz), 128.3, 127.8, 126.3 (q, J = 3.3 Hz), 123.6 (d, J = 3.3 Hz), 119.8 (q, J = 272.4 Hz), 115.5 (d, J = 23.9 Hz), 114.2, 44.6, 33.8, 29.13, 29.07, 28.9, 28.8, 27.7, 25.2, 18.0. HRMS (ESI) m / z: calculated value C 27 H 30 F4O2Na[M+Na] + 485.2074, measured value: 485.2054.

[0092] I-53: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.57-7.51(m,2H,(ArH)2),7.47-7.34(m,4H,(ArH)4),7.22-7.15(m,2H,(ArH)2),6.02(t,J=7.6Hz,1H,C=CH),5.40-5.26( m,2H,CH=CH),3.94(q,J=7.2Hz,1H,COCH),2.04-1.92(m,4H,(CH2)2),1.83-1.72(m,2H,CH2),1.63(d,J=7.2Hz,3H,CH3),1.34-1.15(m,20H,(CH2) 10 ), 0.88 (t, J = 6.8 Hz, 3H, CH3). 13CNMR (101MHz, CDCl3) δ170.6, 159.8 (d, J = 248.9Hz), 140.4 (d, J = 7.6Hz), 135.3 (d, J = 1.2Hz), 134.7 (q ,J=36.4Hz),131.0(d,J=3.8Hz),130.1,129.6,129.0(d,J=2.9Hz),128.5,128.3(d,J=13.4Hz),127. 8,126.3 (q, J = 3.3 Hz), 123.6 (d, J = 3.3 Hz), 119.8 (q, J = 272.1 Hz), 115.5 (d, J = 23.9 Hz), 44.6, 32.0, 29.8, 29.7, 29.6, 29.4, 29.2, 29.1, 28.9, 27.8, 27.2, 27.1, 25.2, 22.7, 18.0, 14.1. HRMS (ESI) m / z: calculated value C 34 H 44 F4O2Na[M+Na] + 583.3169, measured value: 583.3151.

[0093] I-54: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.57-7.52(m,2H,(ArH)2),7.48-7.42(m,3H,(ArH)3),7.40-7.35(m,1 H,ArH),7.24-7.16(m,2H,(ArH)2),6.04(t,J=7.6Hz,1H,C=CH),5.42-5.30(m,4H,(CH=CH)2), 3.96(q,J=7.2Hz,1H,COCH),2.81-2.74(m,2H,CH2),2.10-1.96(m,4H,(CH2)2),1.89-1.34(m ,2H,CH2),1.64(d,J=7.2Hz,3H,CH3),1.38-1.20(m,14H,(CH2)7),0.90(t,J=6.8Hz,3H,CH3). 13C NMR (101MHz, CDCl3) δ170.6, 159.8 (d, J = 248.9Hz), 140.5 (d, J = 7.5Hz), 135.3 (d, J = 1.2Hz), 134.8 (q, J = 36.4Hz) ,131.0(d,J=3.7Hz),130.1(d,J=34.8Hz),130.0(d,J=47.1Hz),128.9(d,J=2.7Hz),128.5(d,J=1.7Hz),128.4( d, J = 13.5 Hz), 128.0 (d, J = 24.1 Hz), 127.8, 126.3 (q, J = 3.3 Hz), 123.7, 123.6, 119.9 (q, J = 271.7 Hz), 115.4 (d, J = 24.0 Hz), 44.6, 31.5, 29.5, 29.4, 29.1, 28.9, 27.7, 27.2, 27.1, 25.6, 25.2, 22.6, 18.0, 14.1. HRMS (ESI) m / z: calculated value C 34 H 42 F4O2Na[M+Na] + 581.3013, measured value: 581.3007.

[0094] I-55: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.56-7.52(m,2H,(ArH)2),7.47-7.37(m,4H,(ArH)4),7.21-7.15 (m,2H,(ArH)2),6.04(t,J=7.6Hz,1H,C=CH),5.43-5.20(m,8H,(CH=CH)4),3.95(q,J=7. 2Hz,1H,COCH),2.85-2.72(m,6H,(CH2)3),2.14-2.02(m,4H,(CH2)2),1.94-1.80(m,2H, CH2),1.63(d,J=7.2Hz,3H,CH3),1.33-1.25(m,6H,(CH2)3),0.88(t,J=6.7Hz,3H,CH3). 13C NMR (101MHz, CDCl3) δ170.6, 159.8 (d, J = 248.9Hz), 140.5 (d, J = 7.7Hz), 135.3 (d, J = 1.2Hz), 134.7 (q, J = 36.3Hz),131.1(d,J=4.0Hz),130.5,129.6,129.0(d,J=2.9Hz),128.9,128.6,128.5,128.4,127.83,12 7.80,128.79,127.7,127.5,125.5 (q, J = 3.4 Hz),123.6 (d, J = 3.5 Hz),119.7 (q, J = 272.4 Hz),115.3 (d, J = 23.9 Hz),44.6,31.5,29.3,27.2,25.65,25.62,25.59,25.4,25.1,22.6,18.1,14.1. HRMS (ESI) m / z: calculated value C 36 H 42 F4O2Na[M+Na] + 605.3013, measured value: 605.3019.

[0095] I-56: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.59-7.54(m,2H,(ArH)2),7.48-7.36(m,4H,(ArH)4),7.25-7.17(m,2H,(ArH)2),6.05(t,J=7.6Hz,1H,C=CH),5.43-5.33( m,2H,CH=CH),3.97(q,J=7.1Hz,1H,COCH),2.10-1.98(m,4H,(CH2)2),1.85-1.74(m,2H,CH2),1.65(d,J=7.1Hz,3H,CH3),1.42-1.13(m,28H,(CH2) 14 ), 0.90 (t, J = 6.8 Hz, 3H, CH3). 13CNMR (101 MHz, CDCl3) (missing four carbon signals) δ 170.6, 159.8 (d, J = 248.9 Hz), 140.4 (d, J = 7.7 Hz), 134.9, 135.3 (d, J = 1.2 Hz), 134.7 (q, J = 36.3 Hz), 131.0 (d, J = 4.0 Hz), 129.9 (d, J = 4.9 Hz), 128.9 (d, J = 2.9 Hz), 128.5, 128.3, 12 7.8,126.3 (q, J = 3.3 Hz), 123.6 (d, J = 3.4 Hz), 119.7 (q, J = 272.4 Hz), 115.4 (d, J = 23.9 Hz), 43.9, 31.9, 29.8, 29.57, 29.56, 29.5, 29.4, 29.3, 29.25, 29.20, 27.8, 26.7, 25.2, 21.2, 17.3, 12.7. HRMS (ESI) m / z: calculated value C 38 H 52 F4O2Na[M+Na] + 639.3795, measured value: 639.3782.

[0096] I-57: light yellow liquid, 1 H NMR(400MHz, CDCl3), δ7.83-7.45(m,9H,(ArH)9),6.02(t,J=7.6Hz,1H,C=CH), 4.00(q,J=7.1Hz,1H,COCH), 1.83-1.72(m,2H,CH2),1.63(d,J=7.1Hz,3H,CH3),1.35-1.10(m,16H,(CH2)8),0.88(t,J=6.9Hz,3H,CH3). 13 C NMR (101 MHz, CDCl3) δ 196.2, 170.7, 139.6, 138.2, 137.4, 134.7 (q, J = 36.3 Hz), 132.6, 131.4, 130.0, 129.5, 129.3, 128.7, 128.4, 126.3 (q, J = 3.4 Hz), 119.8 (q, J = 272.5 Hz), 45.0, 31.9, 29.6, 29.5, 29.3, 29.2, 29.1, 27.8, 25.2, 22.7, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 29 H 35 F3O3Na[M+Na] + 511.2430, measured value: 511.2438.

[0097] I-58: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.82-7.46 (m, 9H, (ArH)9), 6.01 (t, J = 7.6Hz, 1H, C = CH), 3.99 (q, J = 7. 2Hz,1H,COCH),1.82-1.72(m,2H,CH2),1.63(d,J=7.2Hz,3H,CH3),1.28-1.19(m,32H,(CH2) 16 ), 0.88 (t, J = 6.9 Hz, 3H, CH3). 13 C NMR (101 MHz, CDCl3) (missing five carbon signals) δ 196.2, 170.7, 139.6, 138.2, 137.4, 134.7 (q, J = 36.2 Hz), 132.6, 131.4, 130.1, 129.5, 129.3, 128.7, 128.4, 126.3 (q, J = 3.4 Hz), 119.8 (q, J = 272.1 Hz), 45.0, 31.9, 29.72, 29.69, 29.68, 29.6, 29.5, 29.4, 29.2, 29.1, 27.8, 25.2, 22.7, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 37 H 51 F3O3Na[M+Na] + 623.3682, measured value: 623.3686.

[0098] I-59: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.84-7.44(m,9H,(ArH)9),6.02(t,J=7.6Hz,1H,C=CH),5.41-5.29(m,4H,(CH=CH)2),3.99(q,J=7.1Hz,1H,COCH),2.82-2.73 (m,2H,CH2),2.09-2.00(m,4H,(CH2)2),1.86-1.75(m,2H,CH2),1.63(d,J=7.1Hz,3H,CH3),1.37-1.18(m,14H,(CH2)7),0.88(t,J=6.9Hz,3H,CH3). 13C NMR (101 MHz, CDCl3) δ 196.2, 170.7, 139.6, 138.2, 137.4, 134.7 (q, J = 36.3 Hz), 132.6, 131.4, 130.3, 130.0, 129.9, 129.4, 129.3, 128.7, 128.4, 128.2, 127.9, 126.3 (q, J = 3.4 Hz), 119.8 (q, J = 272.3 Hz), 45.0, 31.5, 29.5, 29.3, 29.1, 28.9, 27.7, 27.2, 27.1, 25.6, 25.2, 22.6, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 35 H 43 F3O3Na[M+Na] + 591.3056, measured value: 591.3065.

[0099] I-60: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.79-7.45(m,9H,(ArH)9),6.03(t,J=7.4Hz,1H,C=CH),5.44-5.19(m,8H,(CH=CH)4),3.99(q,J=7.1Hz,1H,COCH),2.86-2.72( m,6H,(CH2)3),2.14-2.02(m,4H,(CH2)2),1.93-1.81(m,2H,CH2),1.63(d ,J=7.1Hz,3H,CH3),1.42-1.21(m,6H,(CH2)3),0.88(t,J=6.9Hz,3H,CH3). 13 C NMR (101MHz, CDCl3) δ196.3, 170.6, 139.5, 138.2, 137.4, 135.0 (q, J = 36.4Hz), 132 .6,131.4,130.5,130.1,129.6,129.5,129.2,128.8,128.6,128.43,128.37,127. 79,127.78,127.7,127.5,125.4 (q, J = 3.4 Hz), 119.7 (q, J = 272.4 Hz), 45.0, 31.5, 29.3, 27.2, 25.64, 25.62, 25.58, 25.4, 25.1, 22.6, 18.1, 14.1. HRMS (ESI) m / z: calculated value C 37 H 43 F3O3Na[M+Na] + 615.3056, measured value: 615.3055.

[0100] I-61: light yellow liquid, 1 H NMR (400MHz, CDCl3), δ7.68-7.61(m,2H,(ArH)2),7.50-7.44(m,2H,(ArH)2),6.97-6.92(m,1H,ArH),6 .88(d,J=9.0Hz,1H,ArH),6.69(dd,J=9.0,2.5Hz,1H,ArH),6.04(t,J=7.6Hz,1H,C=CH),5.43-5.16(m, 8H,(CH=CH)4),3.85(s,2H,COCH2),3.82(s,3H,OCH3),2.85-2.70(m,6H,(CH2)3),2.41(s,3H,CH3),2. 14-2.00(m,4H,(CH2)2),1.99-1.90(m,2H,CH2),1.35-1.25(m,6H,(CH2)3),0.88(t,J=6.7Hz,3H,CH3). 13 CNMR(101MHz, CDCl3)δ168.2,167.3,156.2,139.4,136.3,135.0(q,J=36.4Hz),133.7, 131.2,130.8,130.5,130.2,129.6,129.2,128.7,128.4,127.8,127.8,127.7,127.5,1 25.5 (q, J = 3.4 Hz), 119.8 (q, J = 272.4 Hz), 115.0, 112.1, 111.2, 100.8, 55.6, 31.5, 29.7, 29.3, 27.2, 25.65, 25.62, 25.60, 25.38, 25.35, 22.6, 14.1, 13.3. HRMS (ESI) m / z: calculated value C 40 H 44 ClF3NO4[MH] - 694.2989, measured value: 694.2912.

[0101] Example 1

[0102]

[0103] Preparation of 1-substituted-1-(4-methoxyphenyl)ketone (Compound II)

[0104] Under ice-water bath conditions, carboxylic acids V (1.0 eq, 0.05 mol) of different structures, anisole (1.0 eq, 0.05 mol), and phosphoric acid (1.1 eq, 0.055 mol) were added to a round-bottom eggplant-shaped flask. After being fully cooled to 0°C under magnetic stirring, trifluoroacetic anhydride (4.0 eq, 0.2 mol) was slowly added dropwise. After completion of the addition, the reaction solution was poured into an excess of pre-cooled sodium hydroxide solution and magnetically stirred. Within a few minutes, a white solid was precipitated, which was directly filtered to obtain the product; or a yellow oil was formed and floated on the aqueous solution. The intermediate 1-substituted-1-(4-methoxyphenyl)ketone (II) was obtained by extraction with ethyl acetate and separation by column chromatography.

[0105] Example 2

[0106]

[0107] Preparation of 1-substituted-1-(2,4-dimethoxyphenyl)ketone (Compound III)

[0108] Under ice-water bath, carboxylic acid V (1.0 eq, 0.05 mol) of different structures was dissolved in 1,2-dichloroethane, and thionyl chloride (1.5 eq, 0.075 mol) was slowly added dropwise to the system. After the addition was completed, the temperature was raised to reflux for 2 h, and the solvent was removed in vacuo to obtain an alkyl acid chloride intermediate (Compound IV).

[0109] Under an ice-water bath, 1,3-dimethoxybenzene (1.0 eq, 0.05 mol) and aluminum chloride (1.1 eq, 0.055 mol) were added with 1,2-dichloroethane. After sufficient cooling, the alkyl acyl chloride intermediate (Compound IV) was slowly added. After the addition was complete, the reaction was allowed to proceed at room temperature for 2 h. The reaction solution was quenched with water, extracted with dichloromethane, dried under vacuum, concentrated, and purified by column chromatography to obtain the intermediate 1-substituted-1-(2,4-dimethoxyphenyl)ketone (III).

[0110] Example 3

[0111]

[0112] Preparation of α-trifluoromethyl alkenyl ester (Compound I)

[0113] Under argon, sodium hydride (2.0 eq, 12 mmol), ethyl trifluoroacetate (4.0 eq, 24 mmol), and the intermediate ketone (Compound II or Compound III, 1.0 eq, 6 mmol) were added to a Schlenk flask, and methyl tert-butyl ether (25 mL) was added as solvent. The reaction system was then heated to 55°C and the reaction was continued for 8 hours. Subsequently, the reaction flask was placed in an ice-water bath under argon protection. After the reaction system liquid was completely cooled, the acid chloride (2.0 eq, 12 mmol) was slowly added to the system. After the addition was complete, the reaction was continued for 10 minutes, and then water was added to the reaction system to quench the reaction. The reaction solution was extracted with ethyl acetate, the organic layer was collected, and the solvent was concentrated in vacuo, purified by silica gel column, and enriched to obtain pure α-trifluoromethyl alkenyl ester (I).

[0114] Example 4

[0115] Cytotoxicity assay of compound (I)

[0116] Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay (MTT assay). The compound concentrations were set at high (50 μM), medium (25 μM), and low (12.5 μM). RAW264.7 cells were selected for the assay, and 1×10 cells were seeded per well of a 96-well plate. 5 Cells were cultured in complete DMEM supplemented with 10% fetal bovine serum and 1% penicillin and streptomycin in a 37°C incubator with 5% CO2. 24 hours after inoculation, various concentrations of compound (I) or a positive drug (both dissolved in DMSO, with a final concentration of 0.5%) were added. One hour later, lipopolysaccharide (LPS) was added to a final concentration of 1 μg / mL. After 24 hours of incubation, MTT was added to the culture medium to a final concentration of 0.5 mg / mL and incubated for another 4 hours. The culture medium was then removed, and 150 μL of DMSO was added to each well. The plate was shaken for 10 minutes, and the absorbance at a wavelength of 570 nm was measured using a microplate reader. The specific test results are as follows:

[0117] (1) Aspirin series

[0118] The test results are as follows Figure 1 , the overall structure-activity relationship is 50μM, R 1 When the carbon number is less than 12, it shows strong cytotoxicity, and when it is more than 12, it mostly shows increased cell viability; R 1 -C 16 H 33 (I-7), -C 18 H 37 (I-8) and -C 20 H 41(I-9) was closest to 100% of cell viability; at 25 μM, R 1 Except for compounds I-1 and I-4, the other compounds had no cytotoxicity; under the condition of 12.5 μM, all tested compounds had no cytotoxicity.

[0119]

[0120] (2) Ibuprofen series

[0121] The experimental results showed that I-14(R 2 =-C3H7), I-16(R 2 =-C6H 13 )、I-17(R 2 =-C7H 15 )、I-23(R 2 =-C 15 H 31 ) and I-27(R 2 =C 20 H 41 ) showed increased cell viability; at a concentration of 25 μM, I-16 (R 2 =-C6H 13 )、I-22(R 2 =-C 14 H 29 ) showed cytotoxicity ( Figure 2 ), the remaining compounds had no cytotoxicity at three concentrations, and no clear structure-activity relationship was summarized for this series.

[0122]

[0123] (3) Naproxen series

[0124] All compounds tested in this series were non-cytotoxic at the three tested concentrations ( Figure 3 ).

[0125]

[0126] (4) Flurbiprofen, ketoprofen and indomethacin series

[0127] Except for 50 μM concentration, I-55, I-60 and I-61 reduced cell viability, and the other compounds had no cytotoxicity at the three tested concentrations ( Figure 4 ).

[0128]

[0129]

[0130] Example 5

[0131] Determination of the inhibitory effect of compound (I) on NO release

[0132] The inflammatory effects are associated with many inflammatory mediators, including cytokines, NO, and enzymes, which are released when macrophages produce different phenotypes in response to stimulation. NO, catalyzed by iNOS, is considered an important mediator in the inflammatory process and has been reported to affect the products of the cyclooxygenase metabolic pathway, generating two cyclooxygenase isoforms, COX-1 and COX-2.

[0133] The inflammatory factor NO was detected by Griess reagent. RAW264.7 cell line was used for the assay, and 1×10 cells were seeded into each well of a 96-well plate. 5 Cells were cultured in complete DMEM supplemented with 10% fetal bovine serum and 1% penicillin and streptomycin in a 37°C incubator with 5% CO2. 24 hours after inoculation, 12.5 μM compound (I) or a positive drug (both dissolved in DMSO, final DMSO concentration of 0.5%) was added. One hour later, lipopolysaccharide (LPS) was added to a final concentration of 1 μg / mL. After 24 hours of culture, 100 μL of supernatant was transferred from each well to a 96-well plate, 50 μL of Griess reagent A was added, and the cells were incubated in a 37°C incubator for 10 minutes. Then, 50 μL of Griess reagent B was added and the cells were incubated in a 37°C incubator for 10 minutes. The absorbance at a wavelength of 550 nm was then measured using a microplate reader.

[0134] result Figures 5.1-5.5 Most of the compounds tested can reduce NO concentration to varying degrees and have anti-inflammatory activity. In the aspirin series, compounds I-7, I-8, I-10, I-11 and I-12 are better than the positive control aspirin (Aspirin) ( Figure 5.1 ); In the ibuprofen series, the NO concentration levels in the I-17 and I-30 treatment groups were significantly lower than those in the corresponding positive control ibuprofen ( Figure 5.2 ); In the naproxen series, the NO concentration levels in the I-33, I-35, I-40, I-42 and I-43 treatment groups were significantly lower than those in the model group, and were significantly better than the positive control naproxen (Naproxen), among which compound I-43 had the best inhibitory effect ( Figure 5.3 ); In the flurbiprofen series, except for compounds I-46 and I-51 which had no inhibitory effect, the other compounds were all at the same therapeutic level as the corresponding positive control flurbiprofen (Flurbiprofen), and I-55 was significantly better than flurbiprofen ( Figure 5.4 ); In the ketoprofen series, compound I-60 is significantly better than the corresponding positive drug ketoprofen (Ketoprofen) ( Figure 5.5); Indomethacin series compound I-61 significantly reduced NO release, and its NO inhibition level was comparable to that of indomethacin ( Figure 5.5 ).

[0135] Example 6

[0136] Determination of the inhibitory effect of compound (I) on carrageenan-induced plantar swelling in rats

[0137] Carrageenan-induced rat paw swelling is an acute inflammation model that can be used to evaluate the therapeutic effects of compounds on acute inflammation.

[0138] Male Wistar rats weighing approximately 160-180 g were selected for the experiment. The rats were housed at 23°C, 12 h light / 12 h dark, and had free access to food and water. Compound (I) and the positive drug ibuprofen were mixed in 0.5% sodium carboxymethylcellulose and administered orally at a dose of 20 mg / kg rat body weight. 30 minutes after administration, 0.1 mL of 1% carrageenan in saline solution was injected into the right paw of the rat. The right hind paw volume of the rat was measured before injection and 1, 2, 3, 4, and 5 h after injection. The difference between the initial volume and the volume measured after treatment was the edema volume. The inflammation inhibition rate was calculated using the following formula:

[0139] Edema inhibition rate = (1-Vt / Vc) × 100

[0140] Vt and Vc are the edema volumes of the drug-treated group and the blank group, respectively.

[0141] The test results are shown in Table 1. Compound I-30 exhibited the best inhibitory effect at 1 and 2 hours. Compound I-55 exhibited a good inhibitory effect throughout the entire assay period. All test compounds (I) exhibited comparable or superior inhibition of carrageenan-induced rat paw swelling to that of the positive drug, ibuprofen, demonstrating that the test compounds possess therapeutic effects against acute inflammation.

[0142] Table 1 Inhibitory effect of compound (I) on carrageenan-induced paw swelling in rats

[0143]

[0144] Example 7

[0145] Compound (I) inhibits granulation proliferation induced by cotton ball implantation in mice

[0146] The cotton ball implantation-induced mouse granulation proliferation model is a chronic inflammation model that can be used to evaluate the inhibitory effect of compounds on tissue proliferation in the late stage of inflammation.

[0147] C57Bl / 6 male mice weighing 26-28g were selected and kept at 23°C, 12h light / 12h dark environment, with free access to food and water. Compound (I) or positive drug was mixed in 0.5% sodium carboxymethyl cellulose and administered orally at 10 or 20mg / kg of mouse body weight. A sterile cotton ball weighing 10mg was prepared in advance and soaked in physiological saline containing 1% double antibody. The mice were divided into a vehicle group, a compound (I) treatment group, and a positive drug group. One hour after administration, the mice were anesthetized and fixed for surgery. The skin on the upper back of the mouse was prepared and disinfected, and an incision of about 1cm in length was cut with surgical scissors. A sterile cotton ball was implanted subcutaneously at the scapula and sutured. The entire operation was performed under a sterile environment. For the next 7 days, the drug was administered by gavage once every 24 or 48 hours. On the 8th day, the mice were euthanized, and the cotton balls and attached granulation tissue were carefully removed. The cotton balls were dried at 60°C for 24 hours to a constant weight. The dry weight of the cotton balls in each group was weighed and the inhibition rate was calculated.

[0148] Inhibition rate (%) = 100 × (T model -T treat / T model )

[0149] T model : Weight of granuloma tissue in vehicle group; T treat : The weight of granuloma tissue in the treatment group

[0150] The test results are as follows Figure 6 .

[0151] When administered every 24 or 48 hours, all test compounds (I) and the positive drug group showed lower granulation weights than the vehicle group. However, when administered every 48 hours, compounds I-12, I-30, and I-60 significantly outperformed the positive drug, demonstrating that the tested compound (I) has therapeutic effects on chronic inflammation and hyperplasia and long-lasting efficacy in mice.

[0152] Example 8

[0153] Compound (I) inhibits acetic acid-induced writhing test in mice

[0154] The acetic acid-induced writhing model in mice is a pain test model that can be used to evaluate the analgesic effect of compounds.

[0155] In this study, C57Bl / 6 male mice weighing 26-28g were selected. The mice were kept in an environment of 23°C, 12h light / 12h dark, and were allowed to eat and drink freely. Compound (I) and the positive drug were mixed in 0.5% sodium carboxymethyl cellulose and administered orally at 10 and 20 mg / kg of mouse body weight. 30 minutes after administration, a physiological saline solution containing 0.6% acetic acid was injected into the mouse's abdominal cavity at a dose of 0.1 mL / 10 g of body weight. The number of writhing times of the mice within 20 minutes (6th to 25th minute) after 5 minutes of injection of the acetic acid solution was counted. The results are shown in FIG. Figure 7 .

[0156] At a 10 mg / kg dose, both the tested compound (I) and the positive drug ibuprofen significantly reduced the number of writhings in mice, with compounds I-30 and I-60 showing a more pronounced effect than the positive drug ibuprofen. At a 20 mg / kg dose, both the tested compound (I) and the positive drug ibuprofen significantly reduced the number of writhings in mice, with compounds I-30, I-55, I-60, and I-61 demonstrating superior analgesic effects compared to the positive drug ibuprofen. Overall, compounds I-30 and I-60 demonstrated good analgesic effects at both test concentrations.

[0157] The above embodiments are merely preferred embodiments for fully illustrating the present invention, and the scope of protection thereof is not limited thereto. Equivalent substitutions or modifications made by those skilled in the art based on the present invention are all within the scope of protection of the present invention, and the scope of protection of the present invention shall be subject to the claims.

Claims

1. An α-trifluoromethyl alkenyl ester compound, characterized in that Has the following structure:

2. Use of the α-trifluoromethyl alkenyl ester compound according to claim 1 in the preparation of anti-inflammatory and analgesic drugs.

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