CN104370892B - 1-(7-Methoxvbenzofuran-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl) propenyl - Google Patents
1-(7-Methoxvbenzofuran-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl) propenyl Download PDFInfo
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- CN104370892B CN104370892B CN201410581451.9A CN201410581451A CN104370892B CN 104370892 B CN104370892 B CN 104370892B CN 201410581451 A CN201410581451 A CN 201410581451A CN 104370892 B CN104370892 B CN 104370892B
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- HAIRJNLSNQUYBY-ZDLGFXPLSA-N CC(C)(C1)Oc2c1cc(C(/C(/[n]1ncnc1)=C/c(cccc1)c1OC)O)cc2OC Chemical compound CC(C)(C1)Oc2c1cc(C(/C(/[n]1ncnc1)=C/c(cccc1)c1OC)O)cc2OC HAIRJNLSNQUYBY-ZDLGFXPLSA-N 0.000 description 1
- 0 CC(C)(C1)Oc2c1cc(C(C([n]1ncnc1)=Cc1ccccc1OC)O)cc2* Chemical compound CC(C)(C1)Oc2c1cc(C(C([n]1ncnc1)=Cc1ccccc1OC)O)cc2* 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—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
- 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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- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- C07B2200/13—Crystalline forms, e.g. polymorphs
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Abstract
The present invention relates to 1 (7 methoxyl groups 2 shown in chemical structural formula chemical constitution formula I and I, 2 dimethyl 2,3 Dihydrobenzofuranes 5 bases) 3 (2 methoxyphenyl) 2 (1,2,4 triazole 1 base) 2 propylene 1 alcohol or its salt:(E) 1 (7 methoxyl group 2,2 dimethyl 2,3 Dihydrobenzofuranes 5 base) 3 (2 methoxyphenyls) 2 (1,2,4 triazole 1 bases) molecular structure of 2 propylene 1 alcohol is shown in accompanying drawing, its crystal belongs to monoclinic system, and space group is P21;1 (7 methoxyl groups 2,2 dimethyl 2,3 Dihydrobenzofuranes 5 bases) 3 (2 methoxyphenyl) 2 (1,2,4 triazole 1 base) 2 propylene 1 alcohol or its salt has the activity of anti-human cervical cancer cell (Hela).
Description
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-methoxyphenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol and preparation method thereof
With as the application preparing cancer therapy drug.
Background technology
Chen Wen etc. [Org.Biomol.Chem., 2011,9,4,250 4255] are prepared for a series of containing imidazolyl heterocycle
Coumaran class noval chemical compound, and it is many to human breast cancer cell (MCF-7), human lung carcinoma cell (A549) etc. to test it
Planting the cytotoxicity of human tumor cells, human breast cancer cell (MCF-7), human lung carcinoma cell (A549) are had relatively by part of compounds
Good inhibitory activity, the active best compound IC to human breast cancer cell (MCF-7)50Reach 5.78 μMs.Nagaraju etc.
[Bioorg.Med.Chem.Lett., 2012,22,4,314 4317] ties in the 4-position of coumaran and 7-position
Structure is modified and is obtained a series of benzofuran ketene derivant and to test it thin to Human Prostate Cancer Cells (PC-3), people's pulmonary carcinoma
The inhibitory activity of the multiple cancerous cell such as born of the same parents (NCI-H460), finds that prostate gland cancer cell (PC-3) is had fabulous by part of compounds
Inhibitory activity.Tao Weifeng [Nankai University, Master's thesis, 2002] describe alkene oxazolone (alcohol) compounds containing pyridine radicals
Preparation and bactericidal activity.
Chinese patent describes the preparation of 4-(benzofuran-5-base)-2-benzyl imino thiazole and answering as antitumor drug thereof
With [ZL 201010533786.5], 4-(benzofuran-5-base)-2-benzyl imino thiazole and the application as antitumor drug thereof
[ZL201010533786.5,2012.7.25 authorize] and 2-(2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base) morpholine and
Preparation method and application [201210106643.5,2014.7.23 authorize].
Summary of the invention
It is an object of the invention to provide 1-(7-methoxyl group-2,2-dimethyl-2, the 3-dihydrobenzene shown in chemical constitution formula I or II
And furan-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol or its salt:
Its salt is selected from: hydrochlorate, hydrobromate, sulfate, nitrate, phosphate, mesylate, benzene sulfonate,
Tosilate, malate, lactate, succinate or butene dioic acid salt.
The present invention provide 1-(benzofuran-5-the base)-3-phenyl-2-(1,2,4-triazol-1-yl) shown in chemical constitution formula I or II-
The preparation method of 2-propylene-1-alcohol, it is characterised in that its preparation reaction is as follows:
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxy is obtained by column chromatography for separation
Base phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol and (Z)-1-(7-methoxyl group-2,2-dimethyl-2,3-dihydrobenzene
And furan-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol.
Object of the present invention is to provide (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-
Methoxyphenyl) monocrystal of-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol, its crystal belongs to monoclinic system, and space group is
P 21;Cell parameter is:β=101.758 (5) °;Z=2,Dc=1.312Mg/m3, F (000)=432, μ=0.09mm-1, 3161 considerable measuring point [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,
Object of the present invention is to provide (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-
Methoxyphenyl) preparation method of monocrystal of-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol, it is characterised in that (E)-1-(7-
Methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl)-2-
Propylene-1-alcohol dissolves in organic solvent, and the solution room temperature that obtains places slowly volatilization, separate out after 3~5 days (E)-1-(7-methoxyl group-2,
2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol list
Crystal.
Object of the present invention is to provide (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-
Methoxyphenyl) preparation method of monocrystal of-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol, it is characterised in that You Jirong
Agent one in methanol, ethanol, acetone, ethyl acetate or petroleum ether or two kinds.
Object of the present invention is to provide (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-
Methoxyphenyl) monocrystal of-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol: its molecular structure Atom numbering is as follows:
The present invention compared with prior art has the advantage that 1-(7-methoxyl group-2,2-dimethyl-2, the 3-that the present invention provides
Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol or its salt has anti-human
The activity of cervical cancer cell (Hela).
Accompanying drawing explanation
Fig. 1 be (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,
2,4-triazol-1-yls) molecular structure of-2-propylene-1-alcohol crystals.
Fig. 2 be (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,
2,4-triazol-1-yls) the crystal accumulation figure of-2-propylene-1-alcohol crystals.
Detailed description of the invention
Following example are intended to illustrate rather than limitation of the invention further.
Embodiment 1
(Z/E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,
4-triazol-1-yl) preparation of-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, and reflux 6h.Reaction
Finishing, reactant liquor is washed through washing, saturated common salt, is dried, and precipitation, column chromatography for separation obtains (Z/E)-1-(7-methoxyl group-2,2-
Dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-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-methoxybenzene
Base)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone, 1.6mmol sodium borohydride and 20ml dehydrated alcohol, 40 DEG C of reactions
0.5h, decompression distillation precipitation, column chromatography for separation obtains (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-
Base)-3-(2-methoxyphenyl)-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-methoxyphenyl)-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-methoxyphenyl)-2-(1,2,4-triazole
-1-base)-2-propylene-1-alcohol: m.p.141~144 DEG C,1H NMR (400MHz, CDCl3) δ: 1.49 (s, 6H, 2 × CH3),
2.98 (s, 2H, CH2), 3.79 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 5.67 (s, 1H, CH), 6.58~6.74
(m, 2H, C6H24,6-H), 6.76~7.24 (m, 4H, C6H4), 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-dihydrobenzo furan
Mutter-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol: m.p.154~157 DEG C,1H NMR
(400MHz, CDCl3) δ: 1.52 (s, 6H, 2 × CH3), 3.02 (s, 2H, CH2), 3.61 (s, 3H, OCH3),
3.71 (s, 3H, OCH3), 5.92 (s, 1H, CH), 6.68~6.74 (m, 2H, C6H2), 6.78~7.20 (m, 4H,
C6H4), 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-methoxyphenyl)-2-(1,2,
4-triazol-1-yl)-2-propylene-1-alcohol, to dissolve with ethanol, the solution room temperature obtained places slowly volatilization, separates out after 5~6 days
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazole
-1-base)-2-propylene-1-alcohol monocrystal.
Embodiment 3
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-
Triazol-1-yl) preparation of-2-propylene-1-alcohol monocrystalline
0.5g (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,
2,4-triazol-1-yls)-2-propylene-1-alcohol, to dissolve with methanol, the solution room temperature obtained places slowly volatilization, analyses after 5~6 days
Go out (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-tri-
Azoles-1-base)-2-propylene-1-alcohol monocrystal.
Embodiment 4
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-
Triazol-1-yl) preparation of-2-propylene-1-alcohol monocrystalline
0.5g (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,
2,4-triazol-1-yls)-2-propylene-1-alcohol, with acetone solution, the solution room temperature obtained is placed slowly volatilization, is analysed after 5~6 days
Go out (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-tri-
Azoles-1-base)-2-propylene-1-alcohol monocrystal.
Embodiment 5
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-
Triazol-1-yl) preparation of-2-propylene-1-alcohol monocrystalline
0.5g (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,
2,4-triazol-1-yls)-2-propylene-1-alcohol, to dissolve with ethanol-acetone, the solution room temperature obtained is placed and is slowly volatilized, 5~6 days
Rear precipitation (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,
4-triazol-1-yl)-2-propylene-1-alcohol monocrystal.
Embodiment 6
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-
Triazol-1-yl)-2-propylene-1-alcohol crystals structure determination
Choose 0.42 × 0.40 × 0.32mm3Monocrystalline, on BRUKER SMART APEX 1000CCD diffractometer
Collect diffraction data, utilize Mo K alpha ray (λ=0.071073nm) of graphite monochromator monochromatization, at 150 (2) K
Under withScan mode collects diffraction data.The SAINTPLUS program of utilization Bruker is by data convert, simultaneously
SADABS program is used to carry out empirical absorption correction.Application SHELXS-97 and SHELXL-97 program
[Sheldrick, G.M.SHELXS97 and SHELXL97, University ofGermany, 1997] straight
Connection resolves and refined structure.All of non-hydrogen atom uses complete matrix method of least square to carry out structure refinement.All non-hydrogen
Atom all does anisotropy refine.Theoretical hydrogenation, hydrogen atom isotropism thermal parameter correction.Crystal data and structural parameters
List table 1 in.
Table 1 (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,
2,4-triazol-1-yls) crystal data of-2-propylene-1-alcohol and structural parameters
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-
Triazol-1-yl) the non-hydrogen atom coordinate of-2-propylene-1-alcohol and thermal parameter be listed in table 2, and part bond distance and bond angle are listed in table 3 and table 4.
Table 2 (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,
4-triazol-1-yl) the non-hydrogen atom coordinate of-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) |
Table 3 (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,
4-triazol-1-yl) the part bond distance of-2-propylene-1-alcohol crystals
Table 4 (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,
2,4-triazol-1-yls) part bond angle [°] of-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)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-
Triazol-1-yl)-2-propylene-1-alcohol crystals molecular structure as shown in Figure 1;Structure cell accumulation graph is as shown in Figure 2.
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-
Triazol-1-yl)-2-propylene-1-alcohol crystals belongs to monoclinic system, and space group is P 21.Cell parameter is: β=101.758 (5) °;Z=2,Dc=1.312Mg/m3,
F (000)=432, μ=0.09mm-1, 3161 considerable measuring points [I > 2 σ (I)], the considerable final discrepancy factor of measuring point refine
R1=0.0353, wR2=0.0769, (Δ/σ)max=0.001, S=1.05, (Δ ρ)max=0.20,
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,
4-triazol-1-yl) in-2-propylene-1-alcohol crystals structure, intermolecular is to maintain stablizing of crystal structure by π-π effect.
Embodiment 7
1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazole
-1-base)-2-propylene-1-alcohol or its salt active anticancer 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
Analytic process is with living cells metabolite reducing agent tetrazolium bromide [3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl bromination tetrazole;
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT] based on.MTT is one
Plant the dyestuff that can accept hydrogen atom.Dehydrogenase relevant to NADP in living cells mitochondrion intracellular can be by yellow
MTT changes into insoluble hepatic first a ceremonial jade-ladle, used in libation (formazon), and dead cell is then without this function.Dissolve with DMSO
After formazon, under certain wavelength, measure optical density value by microplate reader, both can quantitatively measure the survival rate of cell.According to
The sample inhibitory action to tumor cell is observed in 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-methoxyphenyl)-2-(1,
2,4-triazol-1-yls)-2-propylene-1-alcohol or its salt:
Cell line: cervical cancer tumer line Hela (offer of Xiangya Medical College, Zhongnan Univ cell bank).
Reagent: tetrazolium bromide (MTT), RPMI RPMI-1640, new-born calf serum, antibiotic (U.S.'s hero's life technology
Company);Pancreatin (AMRESCO company of the U.S.);96 well culture plates (hero Life Technologies, Inc. of the U.S.);Dimethyl sulfoxide is (beautiful
Sigma company of state).
Instrument: HFsafe-1500 type superclean bench, HF151UV type CO2(power Shen, Shanghai scientific instrument are limited for incubator
Company);XSP-15C type inverted microscope (Shanghai rectangular optical instrument company limited);Multiskan MK3 type microplate reader is (beautiful
Thermo company of state);Ultra-pure water preparing instrument (Milli-Q company of the U.S.).
Experimental implementation: sample is for the test of cancerous cell.In experimentation, per sample (p.s.) arranges 5 Concentraton gradient
(1.000 μm ol/mL, 0.300 μm ol/mL, 0.100 μm ol/mL, 0.030 μm ol/mL and 0.010 μm ol/mL), often
Four parallel samples of individual concentration, often parallel 3 times of group experiment, and reached a conclusion by the comparison of blank group.Microplate reader detection is each
Hole OD value, detects wavelength 570nm.
3. antitumor activity evaluation
1) cell inhibitory rate calculates:
2)IC50Value calculates
Sample solution concentration logarithm value and cell inhibitory rate linear regression, utilize software SPSS to calculate sample and suppress the half of cell
Concentration IC50Value.(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,
2,4-triazol-1-yls)-2-propylene-1-alcohol and (Z)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-
Methoxyphenyl)-2-(1,2,4-the triazol-1-yl)-2-propylene-1-alcohol IC to Hela cancerous cell50Be respectively 0.0369mM and
0.0929mM.(E/Z)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxybenzene
Base)-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, the 3-Dihydrobenzofuranes-5-base)-3-(2-shown in chemical constitution formula I and II
Methoxyphenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol or its salt:
Its salt is selected from: hydrochlorate, hydrobromate, sulfate, nitrate, phosphate, mesylate, benzene sulfonate, right
Toluene fulfonate, malate, lactate, succinate or butene dioic acid salt.
2. 1-(benzofuran-5-base)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol described in claim 1
Preparation method, it is characterised in that its preparation reaction is as follows:
(E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxy is obtained by column chromatography for separation
Base phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol and (Z)-1-(7-methoxyl group-2,2-dimethyl-2,3-dihydrobenzene
And furan-5-base)-3-(2-methoxyphenyl)-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-methoxyphenyl)-2-(1,2,
4-triazol-1-yl) monocrystal of-2-propylene-1-alcohol, its crystal belongs to monoclinic system, and space group is P 21;Cell parameter is: β=101.758 (5) °;Z=2,Dc
=1.312Mg/m3, F (000)=432, μ=0.09mm-1, 3161 considerable measuring points [I > 2 σ (I)], considerable measuring point essence
Repair final discrepancy factor R1=0.0353, wR2=0.0769, (Δ/σ)max=0.001, S=1.05,
4. (E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(the 2-methoxy described in claim 3
Base phenyl) preparation method of monocrystal of-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol, it is characterised in that (E)-1-(7-methoxy
Base-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl)-2-propylene
-1-alcohol dissolves in organic solvent, and the solution room temperature obtained places slowly volatilization, separates out (E)-1-(7-methoxyl group-2,2-after 3~6 days
Dimethyl-2,3-Dihydrobenzofuranes-5-base) list of-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol
Crystal.
5. the preparation method of the monocrystal described in claim 4, it is characterised in that organic solvent selected from methanol, ethanol, third
One in ketone, ethyl acetate or petroleum ether or two kinds.
6. 1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(the 2-methoxyl group described in claim 1
Phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol or the application in preparing anti-human cervical cancer medicine of its salt.
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