CN104387373A - 1-(7-propoxy benzofuran-5-group)-3-(2-methoxyl phenyl)-2-(1,2,4-triazole-1- group)acrylketone - Google Patents

1-(7-propoxy benzofuran-5-group)-3-(2-methoxyl phenyl)-2-(1,2,4-triazole-1- group)acrylketone Download PDF

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CN104387373A
CN104387373A CN201410581454.2A CN201410581454A CN104387373A CN 104387373 A CN104387373 A CN 104387373A CN 201410581454 A CN201410581454 A CN 201410581454A CN 104387373 A CN104387373 A CN 104387373A
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propoxy
dimethyl
ketone
propylene
phenyl
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CN104387373B (en
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胡艾希
杨子辉
李婉
闫忠忠
叶姣
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Hunan University
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    • C07—ORGANIC CHEMISTRY
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    • 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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Abstract

The invention relates to 1-(7-propoxy-2,2-dimethyl-2,3-dihydro benzofuran-5-group)-3-(2-methoxyl phenyl)-2-(1,2,4-triazole-1-group)-2-propylene-1-ketone of which the chemical formulas (Z)-I and (E)-II are shown in the description, as well as a salt, namely (Z)-1-(7-propoxy-2,2-dimethyl-2,3-dihydro benzofuran-5-group)-3-(2-methoxyl phenyl)-2-(1,2,4-triazole-1-group)-2-propylene-1-ketone of which the molecular structure is shown in the attached drawing. The single crystal belongs to a triclinic system, and the space group is P1. The invention further discloses application of the 1-(7-propoxy-2,2-dimethyl-2,3-dihydro benzofuran-5-group)-3-(2-methoxyl phenyl)-2-(1,2,4-triazole-1-group)-2-propylene-1-ketone or the salt thereof in preparing anti-cancer drugs.

Description

1-(7-propoxy-cumarone-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl) acrylketone
Technical field
The present invention relates to new compound and its preparation method and application, specifically (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone and preparation method thereof and single crystal structure.
Background technology
Chinese patent [CN102010405B, 2012.7.25 authorize] describe 4-(cumarone-5-base) preparation of-2-benzyl imino thiazole and the application as antitumor drug thereof, Chinese patent [CN 102786515B, 2014.7.23 authorize] describe 2-(2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base) morpholine preparation method and as prepare thymoleptic application.
The present invention is intended to synthesis (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone, and determine its crystalline structure.
Summary of the invention
Chemical structural formula (Z)-I and 1-(the 7-propoxy--2 shown in (E)-I are the object of the present invention is to provide, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone 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 object of the present invention is to provide 1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl) preparation method of-2-propylene-1-ketone, it is characterized in that its preparation feedback is as follows:
(E)-1-(7-propoxy--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-ketone [(E)-I] and (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone [(Z)-I].
The object of the present invention is to provide (Z)-1-(7-propoxy--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-ketone, it belongs to triclinic(crystalline)system, and spacer is unit cell parameters is: β=75.854 (3) °; Z=2, d c=1.285Mg/m3, F (000)=460, μ=0.09mm -1, 3434 considerable measuring points [I > 2 σ (I)], considerable measuring point refine final discrepancy factor R1=0.0410, wR2=0.0890, (Δ/σ) max=0.019, S=0.97, (Δ ρ) max=0.19,
The object of the present invention is to provide (Z)-1-(7-propoxy--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-ketone, molecular structure Atom numbering is as follows:
The object of the present invention is to provide (Z)-1-(7-propoxy--2, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl) preparation method of-2-propylene-1-ketone single crystal, it is characterized in that (Z)-1-(7-propoxy--2, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl)-2-propylene-1-ketone dissolves in methyl alcohol, in ethanol or acetone, the solution room temperature obtained places slowly volatilization, within 5 ~ 7 days, separate out (Z)-1-(7-propoxy--2 afterwards, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl)-2-propylene-1-ketone single crystal.
The object of the present invention is to provide (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone or its salt has antitumour activity.
Accompanying drawing explanation
Fig. 1 is the molecular structure of (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone crystal.
Fig. 2 is the crystal accumulation figure of (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone crystal.
Embodiment
Following examples are intended to the present invention instead of limitation of the invention further are described.
Embodiment 1
The preparation of 1-(7-propoxy--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) preparation of 1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-2-(1,2,4-triazole) ethyl ketone
The bromo-1-of 0.14mol 2-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base) ethyl ketone, 0.16mol 1,2,4-triazole, 4.0mmol PEG600,0.54mol salt of wormwood and 100mL ethyl acetate, backflow 1.5h.Reaction solution suction filtration obtains brown liquid, under condition of ice bath, drips 0.15mol nitric acid, obtains white precipitate, suction filtration, 500mL acetic acid ethyl dissolution, drips 30%NaOH, adjusts pH7, be stirred to solution clarification, separatory, gets organic phase, underpressure distillation, obtains 1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-2-(1,2,4-triazole) ethyl ketone, yield 85.3%, m.p.147 ~ 149 DEG C 1h NMR (400MHz, CDCl 3) δ: 1.03 (t, J=8.0Hz, 3H, CH 3), 1.26 (s, 6H, 2 × CH 3), 1.87 ~ 1.92 (m, 2H, CH 2), 3.09 (s, 2H, CH 2), 4.03 ~ 4.07 (m, 2H, CH 2), 5.66 (s, 2H, CH 2), 7.44 (s, 2H, C 6h 24-H), 7.51 (s, 2H, C 6h 26-H), 8.09 (s, 1H, triazole ring 3-H), 8.51 (s, 1H, triazole ring 5-H).
(2) preparation of (Z/E)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone
3.5mmol 1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-2-(1,2,4-triazole) ethyl ketone, 5.2mmol Benzaldehyde,2-methoxy and 30mL chloroform, stir, add piperidines, backflow 5h.Reaction is finished, reaction solution is through washing, saturated common salt is washed, dry, precipitation, column chromatography for separation obtains (E)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone [(E)-I] and (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone [(Z)-I], yield 59.5%.(E)-I: m.p.192 ~ 193 DEG C, 1h NMR (400MHz, CDCl 3) δ: 1.02 (t, J=7.2Hz, 3H, CH 3), 1.56 (s, 6H, 2 × CH 3), 1.83 ~ 1.88 (m, 2H, CH 2), 3.07 (s, 2H, CH 2), 3.80 (s, 3H, OCH 3), 4.04 (t, J=7.2Hz, 2H, OCH 2), 6.63 ~ 6.81 (m, 2H, C 6h 2), 6.89 ~ 7.40 (m, 4H, C 6h 4), 7.82 (s, 1H, C=CH), 8.21 (s, 1H, triazole ring 3-H), 8.34 (s, 1H, triazole ring 5-H); (Z)-I: m.p.58 ~ 60 DEG C, 1h NMR (400MHz, CDCl 3) δ: 0.99 (t, J=7.2Hz, 3H, CH 3), 1.47 (s, 6H, 2 × CH 3), 1.78 ~ 1.82 (m, 2H, CH 2), 2.89 (s, 2H, CH 2), 3.81 (s, 3H, OCH 3), 3.92 (t, J=7.2Hz, 2H, OCH 2), 6.72 ~ 6.80 (m, 2H, C 6h 2), 6.91 ~ 7.44 (m, 4H, C 6h 4), 7.41 (s, 1H, C=CH), 8.11 (s, 1H, triazole ring 3-H), 8.42 (s, 1H, triazole ring 5-H).
Embodiment 2
(Z) preparation of-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone single crystal
0.5g (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone, with dissolve with ethanol, the solution room temperature obtained places slowly volatilization, within 5 ~ 7 days, separate out (Z)-1-(7-propoxy--2 afterwards, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone single crystal.
Embodiment 3
(Z) preparation of-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone monocrystalline
0.5g (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone, with dissolve with methanol, the solution room temperature obtained places slowly volatilization, within 5 ~ 6 days, separate out (Z)-1-(7-propoxy--2 afterwards, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone single crystal.
Embodiment 4
(Z) preparation of-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone monocrystalline
0.5g (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone, with acetone solution, the solution room temperature obtained places slowly volatilization, within 5 ~ 6 days, separate out (Z)-1-(7-propoxy--2 afterwards, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone single crystal.
Embodiment 5
(Z) preparation of-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone monocrystalline
0.5g (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone, dissolve with ethanol-acetone, the solution room temperature obtained places slowly volatilization, within 5 ~ 6 days, separate out (Z)-1-(7-propoxy--2 afterwards, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone single crystal.
Embodiment 6
(Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone crystalline structure
(1) X-ray structure measures
Choose 0.36 × 0.24 × 0.21mm 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.SHELXS97and 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 (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone and structural parameter
(2) single crystal structure of (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone
(Z)-1-(7-propoxy--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-ketone and thermal parameter list in table 2, and part bond distance and bond angle list in table 3 and table 4.
Table 2 (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base) atomic coordinate (× 10 of-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone crystal 4) and thermal parameter
x y z U(eq)
C(1) 4155(2) 5288(2) 3769(1) 18(1)
C(2) 4697(2) 6579(2) 3297(1) 20(1)
C(3) 4098(2) 7718(2) 3781(1) 22(1)
C(4) 2986(2) 7570(2) 4757(1) 23(1)
C(5) 2458(2) 6305(2) 5249(1) 23(1)
C(6) 3034(2) 5180(2) 4755(1) 21(1)
C(7) 4873(2) 4141(2) 3238(1) 19(1)
C(8) 4517(2) 2842(2) 3371(1) 18(1)
C(9) 5567(2) 1798(2) 2884(1) 18(1)
C(10) 1041(2) 1839(2) 4613(2) 31(1)
C(11) 3011(2) 1360(2) 5026(1) 23(1)
C(12) 6709(2) 2182(2) 1838(1) 17(1)
C(13) 6453(2) 3117(2) 918(1) 18(1)
C(14) 7544(2) 3356(2) -60(1) 18(1)
C(15) 8872(2) 2708(2) -105(1) 18(1)
C(16) 9162(2) 1770(2) 801(1) 17(1)
C(17) 8049(2) 1495(2) 1767(1) 17(1)
C(18) 7601(2) 4198(2) -1213(1) 23(1)
C(19) 9224(2) 4189(2) -1788(1) 21(1)
C(20) 9905(2) 5458(2) -1671(2) 26(1)
C(21) 9591(2) 3878(2) -3003(1) 25(1)
C(22) 6541(2) 7887(2) 1939(2) 33(1)
C(23) 10831(2) 228(2) 1549(1) 23(1)
C(24) 12415(2) -143(2) 1210(2) 27(1)
C(25) 13367(2) 1012(2) 1194(2) 35(1)
N(1) 3205(1) 2310(1) 4091(1) 18(1)
N(2) 1914(1) 2628(2) 3806(1) 26(1)
N(3) 1652(1) 1041(2) 5390(1) 28(1)
O(1) 5491(1) 634(1) 3383(1) 22(1)
O(2) 9857(1) 3046(1) -1104(1) 22(1)
O(3) 10523(1) 1229(1) 644(1) 21(1)
O(4) 5817(1) 6632(1) 2352(1) 29(1)
The bond distance of table 3 (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone crystal
The bond angle [°] of table 4 (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone crystal
Chemical bond Bond angle [°] Chemical bond Bond angle [°]
C(6)-C(1)-C(2) 118.09(14) C(14)-C(18)-H(18A) 111.2
C(4)-C(3)-H(3) 120.3 C(14)-C(18)-H(18B) 111.2
C(8)-C(7)-C(1) 131.95(14) H(18A)-C(18)-H(18B) 109.1
C(8)-C(7)-H(7) 114.0 O(2)-C(19)-C(21) 105.92(13)
C(1)-C(7)-H(7) 114.0 C(21)-C(19)-C(20) 113.02(13)
C(7)-C(8)-N(1) 123.96(14) O(2)-C(19)-C(18) 104.89(11)
C(7)-C(8)-C(9) 121.35(13) C(21)-C(19)-C(18) 114.45(13)
N(1)-C(8)-C(9) 114.25(13) H(22B)-C(22)-H(22C) 109.5
O(1)-C(9)-C(12) 120.95(14) O(3)-C(23)-C(24) 106.99(13)
O(1)-C(9)-C(8) 118.82(14) O(3)-C(23)-H(23A) 110.3
C(12)-C(9)-C(8) 120.19(13) C(23)-C(24)-C(25) 112.83(14)
N(2)-C(10)-N(3) 116.03(14) H(24A)-C(24)-H(24B) 107.8
N(2)-C(10)-H(10) 122.0 C(24)-C(25)-H(25A) 109.5
C(13)-C(12)-C(9) 121.94(13) C(11)-N(1)-N(2) 109.24(12)
C(17)-C(12)-C(9) 117.20(13) C(11)-N(1)-C(8) 128.93(13)
C(13)-C(14)-C(18) 132.33(13) N(2)-N(1)-C(8) 121.42(12)
O(2)-C(15)-C(14) 114.36(14) C(10)-N(2)-N(1) 101.63(13)
O(3)-C(16)-C(17) 126.65(14) C(11)-N(3)-C(10) 102.12(14)
O(3)-C(16)-C(15) 116.16(13) C(16)-O(3)-C(23) 117.04(12)
C(14)-C(18)-C(19) 102.77(12) C(2)-O(4)-C(22) 118.03(13)
(Z) molecular structure of-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone crystal as shown in Figure 1; Structure cell accumulation graph as shown in Figure 2.
(Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone crystal belongs to triclinic(crystalline)system, and spacer is unit cell parameters is: β=75.854 (3) °; Z=2, d c=1.285Mg/m3, F (000)=460, μ=0.09mm-1,3434 considerable measuring points [I > 2 σ (I)], considerable measuring point refine final discrepancy factor R1=0.0410, wR2=0.0890, (Δ/σ) max=0.019, S=0.97, (Δ ρ) max=0.19,
At (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl) in-2-propylene-1-ketone crystalline structure, intermolecular is acted on by π-π maintaining the stable of crystalline structure.
Embodiment 7
(Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone antitumour activity measures
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: (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone.
Clone: cervical cancer tumer line Hela, human lung carcinoma cell (A549) and breast cancer cell line MCF-7 (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.
(Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone is to the IC of human cervical carcinoma (Hela) cell, people's lung cancer (A549) cell and human breast carcinoma (MCF-7) cell 50be respectively 0.0671 μm of ol/mL, 0.0100 μm of ol/mL and 0.0352 μm ol/mL.
Antitumour activity test result display (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone or its salt pair human cervical carcinoma cell (Hela), human lung carcinoma cell (A549) and human breast cancer cell (MCF-7) have good inhibit activities, can be used as the application preparing anticarcinogen.

Claims (5)

1. chemical structural formula (Z)-I and 1-(the 7-propoxy--2 shown in (E)-I, 2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone or its salt:
2. 1-according to claim 1 (7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl) preparation method of-2-propylene-1-ketone, it is characterized in that its preparation feedback is as follows:
(E)-1-(7-propoxy--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-ketone and (Z)-1-(7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone.
3. (Z)-1-(7-propoxy--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-ketone, it is characterized in that its belongs to triclinic(crystalline)system, spacer is unit cell parameters is: β=75.854 (3) °; Z=2, d c=1.285Mg/m3, F (000)=460, μ=0.09mm -1, 3434 considerable measuring points [I > 2 σ (I)], considerable measuring point refine final discrepancy factor R1=0.0410, wR2=0.0890, (Δ/σ) max=0.019, S=0.97, (Δ ρ) max=0.19,
4. (Z)-1-(7-propoxy--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-2-propylene-1-ketone single crystal, it is characterized in that (Z)-1-(7-propoxy--2, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl)-2-propylene-1-ketone dissolves in methyl alcohol, in ethanol or acetone, the solution room temperature obtained places slowly volatilization, within 5 ~ 7 days, separate out (Z)-1-(7-propoxy--2 afterwards, 2-dimethyl-2, 3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1, 2, 4-triazol-1-yl)-2-propylene-1-ketone single crystal.
5. 1-according to claim 1 (7-propoxy--2,2-dimethyl-2,3-Dihydrobenzofuranes-5-base)-3-(2-p-methoxy-phenyl)-2-(1,2,4-triazol-1-yl)-2-propylene-1-ketone or its salt preparing the application in cancer therapy drug.
CN201410581454.2A 2014-10-27 2014-10-27 1-(7-propoxy benzofuran-5-group)-3-(2-methoxyl phenyl)-2-(1,2,4-triazole-1- group)acrylketone Expired - Fee Related CN104387373B (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105859696A (en) * 2015-01-19 2016-08-17 湖南大学 1-furan phenolic ether-3-phenyl-2-(1,2,4-triazole-1-group)-2-acrylketone and application thereof

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008040057A1 (en) * 2006-10-04 2008-04-10 Bionomics Limited Novel benzofuran potassium channel blockers and uses thereof
CN101492426A (en) * 2009-03-11 2009-07-29 湖南大学 Thiazole schiff base containing nitryl, preparation and uses thereof
CN101845026A (en) * 2009-12-30 2010-09-29 湖南大学 5-(4-chlorophenylmethyl)-4-tertiary butyl thiazole derivatives and preparation method and application thereof
CN102010405A (en) * 2010-11-08 2011-04-13 湖南大学 4-(benzofuran-5-yl)-2-benzal aminothiazole and application of 4-(benzofuran-5-base)-2-benzal aminothiazole as antineoplastic agent
CN102675303A (en) * 2011-10-19 2012-09-19 湖南大学 4-alkyl-2-arylamino-5-(1,2,4-triazole-1-group) thiazole and application thereof to preparation of medicaments for resisting cancer
CN103145700A (en) * 2013-04-01 2013-06-12 湖南大学 2-(2-benzyl hydrazono)-4-(benzofuran-5-yl) thiazole and preparation method and application thereof
CN103570643A (en) * 2012-12-03 2014-02-12 湖南大学 N-[4-tertbutyl-5-(2-nitroethyl)thiazole-2-yl]benzamide, preparation method and application
CN105585562A (en) * 2014-10-24 2016-05-18 湖南大学 1-(benzofuran-5-yl)-3-aryl-2-(triazol-1-yl)-propenone and application thereof as anticancer drug

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008040057A1 (en) * 2006-10-04 2008-04-10 Bionomics Limited Novel benzofuran potassium channel blockers and uses thereof
CN101492426A (en) * 2009-03-11 2009-07-29 湖南大学 Thiazole schiff base containing nitryl, preparation and uses thereof
CN101845026A (en) * 2009-12-30 2010-09-29 湖南大学 5-(4-chlorophenylmethyl)-4-tertiary butyl thiazole derivatives and preparation method and application thereof
CN102010405A (en) * 2010-11-08 2011-04-13 湖南大学 4-(benzofuran-5-yl)-2-benzal aminothiazole and application of 4-(benzofuran-5-base)-2-benzal aminothiazole as antineoplastic agent
CN102675303A (en) * 2011-10-19 2012-09-19 湖南大学 4-alkyl-2-arylamino-5-(1,2,4-triazole-1-group) thiazole and application thereof to preparation of medicaments for resisting cancer
CN103570643A (en) * 2012-12-03 2014-02-12 湖南大学 N-[4-tertbutyl-5-(2-nitroethyl)thiazole-2-yl]benzamide, preparation method and application
CN103145700A (en) * 2013-04-01 2013-06-12 湖南大学 2-(2-benzyl hydrazono)-4-(benzofuran-5-yl) thiazole and preparation method and application thereof
CN105585562A (en) * 2014-10-24 2016-05-18 湖南大学 1-(benzofuran-5-yl)-3-aryl-2-(triazol-1-yl)-propenone and application thereof as anticancer drug

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
彭俊梅，等: "5-苄基-4-叔丁基-2-芳氨基噻唑氢溴酸盐的合成、表征及抗肿瘤活性", 《高等学校化学学报》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105859696A (en) * 2015-01-19 2016-08-17 湖南大学 1-furan phenolic ether-3-phenyl-2-(1,2,4-triazole-1-group)-2-acrylketone and application thereof
CN105859696B (en) * 2015-01-19 2018-05-25 湖南大学 1- benzofuranols ether -3- phenyl -2- (1,2,4- triazol-1-yl) -2- propenone and its application

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