CN104370892A - 1-(7-methoxybenzofuran-5-yl)-3-(2-methoxyphenyl)-2-(1,2,4-triazole-1-yl) allyl alcohol - Google Patents

1-(7-methoxybenzofuran-5-yl)-3-(2-methoxyphenyl)-2-(1,2,4-triazole-1-yl) allyl alcohol Download PDF

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CN104370892A
CN104370892A CN201410581451.9A CN201410581451A CN104370892A CN 104370892 A CN104370892 A CN 104370892A CN 201410581451 A CN201410581451 A CN 201410581451A CN 104370892 A CN104370892 A CN 104370892A
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propylene
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alcohol
triazol
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胡艾希
唐玉婷
李婉
叶姣
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Hunan University
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    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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Abstract

The invention relates to 1-(7-methoxyl-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-3-(2-methoxyphenyl)-2-(1,2,4-triazole-1-yl)-2-propylene-1-ol or a salt thereof as shown in the chemical structural formula I and II in the specification. The molecular structure of (E)-1-(7-methoxyl-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-3-(2-methoxyphenyl)-2-(1,2,4-triazole-1-yl)-2-propylene-1-ol is as shown in the figure, the crystal of (E)-1-(7-methoxyl-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-3-(2-methoxyphenyl)-2-(1,2,4-triazole-1-yl)-2-propylene-1-ol belongs to a monoclinic crystal system, and the space group is P21. 1-(7-methoxyl-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-3-(2-methoxyphenyl)-2-(1,2,4-triazole-1-yl)-2-propylene-1-ol or the salt thereof has activity of resisting human cervical carcinoma cells (Hela).

Description

1-(7-Methoxvbenzofuran-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl) vinylcarbinol
Technical field
The present invention relates to new compound of a class and its preparation method and application, specifically 1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol and preparation method thereof and as the application preparing cancer therapy drug.
Background technology
[the Org.Biomol.Chem. such as Chen Wen, 2011,9,4250 – 4255] prepare a series of coumaran class new compound containing imidazolyl heterocycle, and test its cytotoxicity to various human tumour cells such as human breast cancer cell (MCF-7), human lung carcinoma cells (A549), part of compounds has good inhibit activities to human breast cancer cell (MCF-7), human lung carcinoma cell (A549), and active best compound is to the IC of human breast cancer cell (MCF-7) 50reach 5.78 μMs.[the Bioorg.Med.Chem.Lett. such as Nagaraju, 2012,22,4314 – 4317] to carry out structural modification in the 4-position of coumaran and 7-position and obtain a series of cumarone ketene derivative and test its inhibit activities to multiple cancer cells such as Human Prostate Cancer Cells (PC-3), human lung carcinoma cells (NCI-H460), find that part of compounds has fabulous inhibit activities to prostate cancer cell (PC-3).Tao Weifeng [Nankai University, Master's thesis, 2002] describes preparation containing alkene oxazolone (alcohol) compounds of pyridyl and fungicidal activity.
Chinese patent describe 4-(cumarone-5-base)-2-benzyl imino thiazole preparation and as the application [ZL 201010533786.5] of antitumor drug, 4-(cumarone-5-base)-2-benzyl imino thiazole and the application [ZL201010533786.5 as antitumor drug thereof, 2012.7.25 authorize] and 2-(2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base) morpholine and preparation method thereof and application [201210106643.5,2014.7.23 authorizes].
Summary of the invention
The object of this invention is to provide 1-(the 7-methoxyl group-2 shown in chemical structural formula I or II, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol or its salt:
Its salt is selected from: hydrochloride, hydrobromate, vitriol, nitrate, phosphoric acid salt, mesylate, benzene sulfonate, tosilate, malate, lactic acid salt, succinate or butene dioic acid salt.
The invention provides the preparation method of 1-(cumarone-5-base)-3-phenyl-2-(1,2,4-the triazol-1-yl)-2-propylene-1-alcohol shown in chemical structural formula I or II, it is characterized in that its preparation feedback is as follows:
(E)-1-(7-methoxyl group-2 is obtained by column chromatography for separation, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol and (Z)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol.
The object of the present invention is to provide (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl) single crystal of-2-propylene-1-alcohol, its crystal belongs to oblique system, and spacer is P 2 1; Unit cell parameters is: β=101.758 (5) °; Z=2, d c=1.312Mg/m 3, F (000)=432, μ=0.09mm -1, 3161 considerable measuring points [I > 2 σ (I)], considerable measuring point refine final discrepancy factor R1=0.0353, wR2=0.0769, (Δ/σ) max=0.001, S=1.05, (Δ ρ) max=0.20,
The object of the present invention is to provide (E)-1-(7-methoxyl group-2, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl) preparation method of single crystal of-2-propylene-1-alcohol, it is characterized in that (E)-1-(7-methoxyl group-2, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl)-2-propylene-1-alcohol dissolves in organic solvent, the solution room temperature obtained places slowly volatilization, within 3 ~ 5 days, separate out (E)-1-(7-methoxyl group-2 afterwards, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl)-2-propylene-1-alcohol single crystal.
The object of the present invention is to provide (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl) preparation method of single crystal of-2-propylene-1-alcohol, it is characterized in that organic solvent is selected from one in methyl alcohol, ethanol, acetone, ethyl acetate or sherwood oil or two kinds.
The object of the present invention is to provide (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl) single crystal of-2-propylene-1-alcohol: its molecular structure Atom numbering is as follows:
The present invention compared with prior art tool has the following advantages: 1-provided by the invention (7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol or its salt has the activity of anti-human cervical cancer cell (Hela).
Accompanying drawing explanation
Fig. 1 is the molecular structure of (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol crystals.
Fig. 2 is the crystal accumulation figure of (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol crystals.
Embodiment
Following examples are intended to the present invention instead of limitation of the invention further are described.
Embodiment 1
(Z/E) preparation of-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol (II/I)
3.5mmol 1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-2-(1,2,4-triazol-1-yl) ethyl ketone, 5.2mmol Benzaldehyde,2-methoxy and 30mL chloroform, stir, drip catalytic amount piperidines, backflow 6h.Reaction is finished, reaction solution is through washing, saturated common salt is washed, drying, precipitation, column chromatography for separation obtains (Z/E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone.
0.79mmol (Z/E)-1-(7-methoxyl group-2, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl)-2-propylene-1-ketone, 1.6mmol sodium borohydride and 20ml dehydrated alcohol, 40 DEG C of reaction 0.5h, underpressure distillation precipitation, column chromatography for separation obtains (E)-1-(7-methoxyl group-2, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl)-2-propylene-1-alcohol and (Z)-1-(7-methoxyl group-2, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl)-2-propylene-1-alcohol, yield 86.7%.(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol: m.p.141 ~ 144 DEG C, 1h NMR (400MHz, CDCl 3) δ: 1.49 (s, 6H, 2 × CH 3), 2.98 (s, 2H, CH 2), 3.79 (s, 3H, OCH 3), 3.83 (s, 3H, OCH 3), 5.67 (s, 1H, CH), 6.58 ~ 6.74 (m, 2H, C 6h 24,6-H), 6.76 ~ 7.24 (m, 4H, C 6h 4), 7.03 (s, 1H, CCH), 7.65 (s, 1H, triazole ring 3-H), 8.03 (s, 1H, triazole ring 5-H); (Z)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol: m.p.154 ~ 157 DEG C, 1h NMR (400MHz, CDCl 3) δ: 1.52 (s, 6H, 2 × CH 3), 3.02 (s, 2H, CH 2), 3.61 (s, 3H, OCH 3), 3.71 (s, 3H, OCH 3), 5.92 (s, 1H, CH), 6.68 ~ 6.74 (m, 2H, C 6h 2), 6.78 ~ 7.20 (m, 4H, C 6h 4), 7.13 (s, 1H, CCH), 7.95 (s, 1H, triazole ring 3-H), 8.15 (s, 1H, triazole ring 5-H).
Embodiment 2
0.5g (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol, with dissolve with ethanol, the solution room temperature obtained places slowly volatilization, within 5 ~ 6 days, separate out (E)-1-(7-methoxyl group-2 afterwards, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol single crystal.
Embodiment 3
(E) preparation of-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol monocrystalline
0.5g (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol, with dissolve with methanol, the solution room temperature obtained places slowly volatilization, within 5 ~ 6 days, separate out (E)-1-(7-methoxyl group-2 afterwards, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol single crystal.
Embodiment 4
(E) preparation of-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol monocrystalline
0.5g (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol, with acetone solution, the solution room temperature obtained places slowly volatilization, within 5 ~ 6 days, separate out (E)-1-(7-methoxyl group-2 afterwards, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol single crystal.
Embodiment 5
(E) preparation of-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol monocrystalline
0.5g (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol, dissolve with ethanol-acetone, the solution room temperature obtained places slowly volatilization, within 5 ~ 6 days, separate out (E)-1-(7-methoxyl group-2 afterwards, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol single crystal.
Embodiment 6
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol crystals structure determination
Choose 0.42 × 0.40 × 0.32mm 3monocrystalline, diffraction data collected by BRUKER SMART APEX 1000CCD diffractometer, utilizes the Mo K alpha-ray (λ=0.071073nm) of graphite monochromator monochromatization, under 150 (2) K with scan mode collects diffraction data.Use the SAINTPLUS program of Bruker by reduction of data, use SADABS program to carry out empirical absorption correction simultaneously.Application SHELXS-97 and SHELXL-97 program [Sheldrick, G.M.SHELXS97 and SHELXL97, University of germany, 1997] direct method is resolved and refined structure.All non-hydrogen atoms adopt complete matrix method of least squares to carry out structure refinement.All non-hydrogen atoms all do anisotropy refine.Theoretical hydrogenation, the correction of hydrogen atom isotropy thermal parameter.Crystal data and structural parameter list table 1 in.
The crystal data of table 1 (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol and structural parameter
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl) the non-hydrogen atom coordinate of-2-propylene-1-alcohol and thermal parameter list in table 2, and part bond distance and bond angle list in table 3 and table 4.
Table 2 (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base) the non-hydrogen atom coordinate of-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol and thermal parameter
x y z U(eq)
C(1) -651(3) 3335(2) 5030(1) 20(1)
C(2) -2343(3) 4014(2) 5123(2) 24(1)
C(3) -2204(4) 4592(2) 6018(2) 28(1)
C(4) -417(4) 4498(2) 6826(2) 27(1)
C(5) 1247(3) 3801(2) 6740(2) 22(1)
C(6) 1163(3) 3209(2) 5854(1) 19(1)
C(7) 2953(3) 2504(2) 5714(1) 18(1)
C(8) 3996(3) 1818(2) 6387(2) 17(1)
C(9) 3434(3) 1520(1) 7409(1) 18(1)
C(10) 8090(3) 719(2) 5296(2) 23(1)
C(11) 7216(3) 599(2) 6730(2) 23(1)
C(12) 5205(3) 1772(2) 8357(1) 17(1)
C(13) 6868(3) 2497(2) 8338(1) 19(1)
C(14) 8453(3) 2658(2) 9230(1) 19(1)
C(15) 8375(3) 2112(2) 10120(1) 18(1)
C(16) 6708(3) 1401(2) 10167(1) 19(1)
C(17) 5133(3) 1240(2) 9272(1) 18(1)
C(18) 10464(3) 3346(2) 9468(2) 24(1)
C(19) 10978(3) 3343(2) 10657(1) 20(1)
C(20) 13402(3) 3345(2) 11162(2) 29(1)
C(21) 9749(3) 4206(2) 11086(2) 25(1)
C(22) -2400(4) 2796(2) 3334(2) 30(1)
C(23) 4852(4) 360(2) 11213(2) 32(1)
N(1) 5767(3) 1223(1) 6133(1) 18(1)
N(2) 6322(3) 1305(1) 5188(1) 22(1)
N(3) 8729(3) 264(1) 6236(1) 24(1)
O(1) 3008(2) 430(1) 7424(1) 21(1)
O(2) 10041(2) 2353(1) 10934(1) 22(1)
O(3) 6753(2) 936(1) 11101(1) 26(1)
O(4) -567(2) 2747(1) 4182(1) 25(1)
The part bond distance of table 3 (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol crystals
The part bond angle [°] of table 4 (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol crystals
Chemical bond Bond angle [°] Chemical bond Bond angle [°]
O(4)-C(1)-C(2) 125.29(17) C(11)-N(3)-C(10) 102.04(17)
C(4)-C(5)-H(5) 119.3 C(15)-O(2)-C(19) 105.79(13)
C(5)-C(6)-C(7) 122.89(17) C(1)-O(4)-C(22) 117.69(16)
C(8)-C(7)-C(6) 127.00(16) O(4)-C(1)-C(6) 114.51(17)
C(6)-C(7)-H(7) 116.5 C(8)-C(7)-H(7) 116.5
C(7)-C(8)-C(9) 126.85(17) C(7)-C(8)-N(1) 119.34(16)
O(1)-C(9)-C(8) 109.76(15) N(1)-C(8)-C(9) 113.69(16)
C(8)-C(9)-C(12) 115.03(16) O(1)-C(9)-C(12) 107.55(15)
C(8)-C(9)-H(9) 108.1 O(1)-C(9)-H(9) 108.1
N(2)-C(10)-N(3) 115.29(17) N(2)-C(10)-H(10) 122.4
N(3)-C(10)-H(10) 122.4 N(3)-C(11)-N(1) 111.27(17)
N(3)-C(11)-H(11) 124.4 N(1)-C(11)-H(11) 124.4
C(13)-C(12)-C(17) 119.79(17) C(13)-C(12)-C(9) 122.60(16)
C(17)-C(12)-C(9) 117.61(17) C(15)-C(14)-C(18) 106.91(16)
C(13)-C(14)-C(18) 132.58(17) O(2)-C(15)-C(14) 113.86(17)
O(2)-C(15)-C(16) 124.25(16) O(3)-C(16)-C(15) 116.71(17)
O(3)-C(16)-C(17) 125.91(18) C(14)-C(18)-H(18A) 111.4
C(14)-C(18)-C(19) 101.67(15) O(2)-C(19)-C(21) 106.46(14)
C(19)-C(18)-H(18A) 111.4 O(2)-C(19)-C(18) 104.25(15)
O(2)-C(19)-C(20) 107.26(16) C(21)-C(19)-C(18) 111.41(18)
C(20)-C(19)-C(21) 111.21(17) C(11)-N(1)-C(8) 129.51(15)
C(11)-N(1)-N(2) 108.87(15) C(10)-N(2)-N(1) 102.53(16)
N(2)-N(1)-C(8) 121.41(15) C(16)-O(3)-C(23) 117.15(15)
(E) molecular structure of-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol crystals as shown in Figure 1; Structure cell accumulation graph as shown in Figure 2.
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol crystals belongs to oblique system, and spacer is P 2 1.Unit cell parameters is: β=101.758 (5) °; Z=2, d c=1.312Mg/m 3, F (000)=432, μ=0.09mm -1, 3161 considerable measuring points [I > 2 σ (I)], considerable measuring point refine final discrepancy factor R1=0.0353, wR2=0.0769, (Δ/σ) max=0.001, S=1.05, (Δ ρ) max=0.20,
At (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl) in-2-propylene-1-alcohol crystals structure, intermolecular is acted on by π-π maintaining the stable of crystalline structure.
Embodiment 7
1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol or its salt antitumour activity measure
1. anti-tumor activity principle
Mtt assay biological activity test, also known as MTT colorimetry, is a kind of method detecting cell survival and growth.MTT analytical method is with living cells metabolize thing reductive agent tetrazolium bromide [3-(4,5-dimethyl-2-thiazole)-2,5-phenylbenzene bromination tetrazoles; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT] based on.MTT is a kind of dyestuff that can accept hydrogen atom.The MTT of yellow can be changed into insoluble hepatic first a ceremonial jade-ladle, used in libation (formazon) by desaturase relevant to NADP in viable cell plastosome in cell, and dead cell is then without this function.After dissolving formazon with DMSO, under certain wavelength, measure optical density value by microplate reader, both quantitatively can measure the survival rate of cell.Sample is observed to the restraining effect of tumour cell according to the change of optical density value.
2. anti-tumor activity experiment
Sample: (E/Z) 1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol or its salt:
Clone: cervical cancer tumer line Hela (Xiangya Medical College, Zhongnan Univ cell bank provides).
Reagent: tetrazolium bromide (MTT), RPMI RPMI-1640, new-born calf serum, microbiotic (hero Life Technologies, Inc. of the U.S.); Pancreatin (AMRESCO company of the U.S.); 96 well culture plates (hero Life Technologies, Inc. of the U.S.); Dimethyl sulfoxide (DMSO) (Sigma Co., USA).
Instrument: HFsafe-1500 type Bechtop, HF151UV type CO 2incubator (Shanghai Lishen Scientific Equipment Co., Ltd.); XSP-15C type inverted microscope (the rectangular opticinstrument company limited in Shanghai); Multiskan MK3 type microplate reader (Thermo company of the U.S.); Ultrapure water preparing instrument (Milli-Q company of the U.S.).
Experimental implementation: sample is for the test of cancer cells.In an experimentation, per sample (p.s.) arranges 5 concentration gradients (1.000 μm of ol/mL, 0.300 μm of ol/mL, 0.100 μm of ol/mL, 0.030 μm of ol/mL and 0.010 μm ol/mL), each concentration four parallel samples, often parallel 3 times of group experiment, and reached a conclusion by the contrast of blank group.Microplate reader detects each hole OD value, determined wavelength 570nm.
3. antitumor activity evaluation
1) cell inhibitory rate calculates:
2) IC 50value calculates
Sample solution concentration logarithmic value and cell inhibitory rate linear regression, utilize software SPSS to calculate sample to the half-inhibition concentration IC of cell 50value.(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol and (Z)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol is to the IC of Hela cancer cells 50be respectively 0.0369mM and 0.0929mM.(E/Z)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol or its salt can be used for preparing anticarcinogen.

Claims (6)

1. 1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-the triazol-1-yl)-2-propylene-1-alcohol shown in chemical structural formula I and I or its salt:
Its salt is selected from: hydrochloride, hydrobromate, vitriol, nitrate, phosphoric acid salt, mesylate, benzene sulfonate, tosilate, malate, lactic acid salt, succinate or butene dioic acid salt.
2. the preparation method of 1-according to claim 1 (cumarone-5-base)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol, is characterized in that its preparation feedback is as follows:
(E)-1-(7-methoxyl group-2 is obtained by column chromatography for separation, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol and (Z)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol.
3. (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl) single crystal of-2-propylene-1-alcohol, its crystal belongs to oblique system, and spacer is P2 1; Unit cell parameters is: β=101.758 (5) °; Z=2, d c=1.312Mg/m 3, F (000)=432, μ=0.09mm -1, 3161 considerable measuring points [I > 2 σ (I)], considerable measuring point refine final discrepancy factor R1=0.0353, wR2=0.0769, (Δ/σ) max=0.001, S=1.05, (Δ ρ) max=0.20,
4. (E)-1-(7-methoxyl group-2 according to claim 3, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl) preparation method of single crystal of-2-propylene-1-alcohol, it is characterized in that (E)-1-(7-methoxyl group-2, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl)-2-propylene-1-alcohol dissolves in organic solvent, the solution room temperature obtained places slowly volatilization, within 3 ~ 6 days, separate out (E)-1-(7-methoxyl group-2 afterwards, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl) single crystal of-2-propylene-1-alcohol.
5. the preparation method of single crystal according to claim 4, is characterized in that organic solvent is selected from one in methyl alcohol, ethanol, acetone, ethyl acetate or sherwood oil or two kinds.
6. 1-according to claim 1 (7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol or its salt has the activity of anti-human cervical cancer cell (Hela).
CN201410581451.9A 2014-10-27 2014-10-27 1-(7-Methoxvbenzofuran-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl) propenyl Expired - Fee Related CN104370892B (en)

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CN111574466A (en) * 2020-06-05 2020-08-25 浙江工业大学 Novel allyl benzoate compound containing triazole as well as preparation method and application thereof
CN111620827A (en) * 2020-06-05 2020-09-04 浙江工业大学 Novel allyl ether compound containing triazole as well as preparation method and application thereof
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CN111620827B (en) * 2020-06-05 2021-09-21 浙江工业大学 Allyl ether compound containing triazole and preparation method and application thereof

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