CN105585563A - 1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)propenol and application thereof - Google Patents

1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)propenol and application thereof Download PDF

Info

Publication number
CN105585563A
CN105585563A CN201410573025.0A CN201410573025A CN105585563A CN 105585563 A CN105585563 A CN 105585563A CN 201410573025 A CN201410573025 A CN 201410573025A CN 105585563 A CN105585563 A CN 105585563A
Authority
CN
China
Prior art keywords
alkyl
propylene
alcohol
phenyl
benzofuran
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201410573025.0A
Other languages
Chinese (zh)
Other versions
CN105585563B (en
Inventor
胡艾希
李婉
杨子辉
丁娜
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hunan University
Original Assignee
Hunan University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hunan University filed Critical Hunan University
Priority to CN201410573025.0A priority Critical patent/CN105585563B/en
Publication of CN105585563A publication Critical patent/CN105585563A/en
Application granted granted Critical
Publication of CN105585563B publication Critical patent/CN105585563B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to 1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propen-1-ol represented by a chemical structural formula I or II shown in the description or salts thereof and an application of the 1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propen-1-ol or salts thereof in preparation of anti-cancer drugs, wherein R is selected from hydrogen, deuterium, C1-C2alkyl and C3-C4alkyl; X1 and X5 each is selected from hydrogen, deuterium, C1-C2alkyl, C3-C4alkyl, hydroxyl, C1-C2alkoxyl, C3-C4alkoxyl, fluorine, chlorine, bromine or nitro; X3 is selected from hydrogen, deuterium, C1-C2alkyl, C3-C4alkyl, hydroxyl, C1-C2alkoxyl, C3-C4alkoxyl, fluorine, chlorine, bromine or nitro; and X2 and X4 each is selected from hydrogen, deuterium, C1-C2alkyl, C3-C4alkyl or nitro.

Description

1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl) propenyl and application thereof
Technical field
The present invention relates to compound that a class is new and its preparation method and application, specifically 1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol and preparation method thereof with it as the application of preparing cancer therapy drug.
Background technology
Overmeyer etc. [Mol.Cancer, 2011,10:69], taking chalcone (1) as parent, carry out structure of modification and have synthesizedA series of chalcone analogs (2～4), compound 2[Pharm.Biol., 2012,50 (12), 1551 – 1560] have oneFixed anti-human chronic myelocytic leukemia (K562) activity, compound 3[Bioorg.&Med.Chem., 2009,17,8168 – 8173] there is anti-inflammatory, anti-oxidant and antibacterial activity, and originally nontoxic to normal cell based. Compound 4[Mol.Cancer, 2011,10:69] can cause the apoptosis of glioblastoma cell. ChenWen etc. [Org.Biomol.Chem.,2011,9,4250 – 4255] synthesize a series of coumaran imidazole salt compounds 5, and tested it to human milkThe cytotoxicity of the various human tumour cells such as adenocarcinoma cell (MCF-7), human lung carcinoma cell (A549), wherein compound 5a coupleThe IC of human breast cancer cell (MCF-7) and human lung carcinoma cell (A549)50Be respectively 7.95 μ M and 12.35 μ M.
Nagaraju etc. [Bioorg.Med.Chem.Lett., 2012,22,4314 – 4317] are closed as initiation material by resorcinolThe benzofuranyl propenone analog derivative 6～11 becoming, and tested that it is thin to Human Prostate Cancer Cells (PC-3), people's lung cancerThe inhibition activity of the multiple cancer cells such as born of the same parents (NCI-H460), part of compounds is to prostate gland cancer cell (PC-3) and lung carcinoma cell(NCI-H460) there is good inhibition active. Tao Weifeng [Nankai University, Master's thesis, 2002] has described containing pyridine radicals and threeThe propylene oxazolone (12) of azoles base, propylene azoles alcohol (13) compounds synthetic, compound 12 has certain bactericidal activity, chemical combinationThing 13 has plant growth regulation.
Chinese patent has been described the preparation of 4-(benzofuran-5-yl)-2-benzyl imino thiazole and answering as antineoplastic thereofWith [ZL201010533786.5], 4-(benzofuran-5-yl)-2-benzyl imino thiazole and as the application of antineoplastic[ZL201010533786.5,2012.7.25 authorize] and 2-(2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl) morpholine andPreparation method and application [ZL201210106643.5,2014.7.23 authorizes].
Summary of the invention
The object of this invention is to provide the 1-shown in chemical structural formula I or II (benzofuran-5-yl)-3-phenyl-2-(1,2,4-Triazol-1-yl)-2-propylene-1-alcohol or its salt:
Wherein, R is selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl; X1、X5Be selected from: hydrogen,Deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl orBranched alkoxy, fluorine, chlorine, bromine or nitro; X3Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or side chainAlkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl or branched alkoxy, fluorine, chlorine, bromine or nitro; X2、X4Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, or nitro; Its salt is selected from: hydrochloride,Hydrobromate, sulfate, nitrate, phosphate, mesylate, benzene sulfonate, tosilate, malate,Lactate, succinate or butene dioic acid salt.
Shown in formula I-1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol is (Z)-1-(benzeneAnd furans-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol; Shown in formula II-1-(benzofuran-5-yl)-3-Phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol is (E)-1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazole-1-Base)-2-propylene-1-alcohol.
The object of this invention is to provide the 1-shown in chemical structural formula III or IV (benzofuran-5-yl)-3-phenyl-2-(1,2,4-Triazol-1-yl)-2-propylene-1-alcohol:
Wherein, X1、X5Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl or branched alkoxy, fluorine, chlorine, bromine or nitro; X3Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl or side chain alcoxylBase, fluorine, chlorine, bromine or nitro; X2、X4Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl,Or nitro.
The object of this invention is to provide the 1-shown in chemical structural formula V or VI (benzofuran-5-yl)-3-phenyl-2-(1,2,4-Triazol-1-yl)-2-propylene-1-alcohol:
Wherein, X1、X5Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl or branched alkoxy, fluorine, chlorine, bromine or nitro; X3Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl or side chain alcoxylBase, fluorine, chlorine, bromine or nitro; X2、X4Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl,Or nitro.
The object of this invention is to provide the 1-shown in chemical structural formula VII or VIII (benzofuran-5-yl)-3-phenyl-2-(1,2,4-Triazol-1-yl)-2-propylene-1-alcohol:
Wherein, X1、X5Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl or branched alkoxy, fluorine, chlorine, bromine or nitro; X3Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl or side chain alcoxylBase, fluorine, chlorine, bromine or nitro; X2、X4Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl,Or nitro.
The invention provides (benzofuran-5-yl)-3-phenyl-2-of the 1-shown in chemical structural formula I or II (1,2,4-triazol-1-yl)-The preparation method of 2-propylene-1-alcohol, is characterized in that its preparation feedback is as follows:
Wherein, R is selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl; X1、X5Be selected from: hydrogen,Deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl orBranched alkoxy, fluorine, chlorine, bromine or nitro; X3Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or side chainAlkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl or branched alkoxy, fluorine, chlorine, bromine or nitro; X2、X4Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, or nitro;
The invention provides (benzofuran-5-yl)-3-phenyl-2-of the 1-shown in chemical structural formula I～VIII (1,2,4-triazol-1-yl)-2-Propylene-1-alcohol is in the application of preparing in antineoplastic.
The present invention compared with prior art tool has the following advantages: the invention provides the 1-(benzofuran-5-shown in chemical formula IBase)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol has anti-human cervical cancer cell (Hela), human breast cancer cellAnd the activity of human lung carcinoma cell (A549) (MCF-7).
Detailed description of the invention
Following examples are intended to illustrate the present invention instead of limitation of the invention further.
Embodiment 1
(Z/E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-aminomethyl phenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B1 and (E)-B1]
3.5mmol1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(1,2,4-triazole) ethyl ketone (D1), 5.2Mmol benzaldehyde and 30mL chloroform, stir, drip catalytic amount piperidines, backflow 6h. After reaction finishes, reactant liquor warpWashing, saturated common salt washing, dry, precipitation, column chromatography for separation obtains product A 1.
In 100ml there-necked flask, add 0.79mmol compd A 1,1.6mmol sodium borohydride, 20ml absolute ethyl alcohol,40 DEG C of reaction 15min, decompression distillation precipitation, column chromatography for separation obtains product, yield 89.2%. (E)-B1:m.p.120～125 DEG C,1HNMR(400MHz，CDCl3)δ:1.49(s，6H，2×CH3)，2.28(s，3H，CH3)，2.98(s，2H，CH2)，3.80(s，3H，OCH3)，5.60(s，1H，CH)，6.65(s，1H，C6H24-H)，6.71(d，J＝8.0Hz，2H，C6H43,5-H)，6.72(s，1H，C6H26-H)，6.84(s，1H，CCH)，7.01(d，J＝8.0Hz，2H，C6H42,6-H), 7.61 (s, 1H, triazole ring 3-H), 8.08 (s, 1H, triazole ring 5-H); (Z)-B1:m.p.69～71 DEG C,1HNMR(400MHz，CDCl3)δ:1.48(s，6H，2×CH3)，2.27(s，3H，CH3)，2.99(s，2H，CH2)，3.81(s，3H，OCH3)，5.12(s，1H，CH)，6.68(s，1H，C6H24-H)，6.72(d，J＝8.0Hz，2H，C6H43，5-H)，6.82(s，1H，C6H26-H)，6.92(d，J＝8.0Hz，2H，C6H42，6-H)，7.06(s, 1H, CCH), 7.46 (s, 1H, triazole ring 3-H), 7.98 (s, 1H, triazole ring 5-H).
Embodiment 2
(Z/E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(2-methoxyphenyl)-2-(1,2,4-triazole-1-yl) preparation of-2-propylene-1-alcohol [(Z)-B2 and (E)-B2]
Operation is with embodiment 1. Reaction 0.5h, yield 86.7%. (E)-B2:m.p.141～144 DEG C,1HNMR(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)-B2:m.p. 154～157℃，1HNMR(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 3
(Z/E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-fluorophenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B3 and (E)-B3]
Operation is with embodiment 1. Reaction 0.5h, yield 85.0%. (E)-B3: liquid,1HNMR(400MHz，CDCl3)δ:1.28(s，6H，2×CH3)，2.89(s，2H，CH2)，3.71(s，3H，OCH3)，5.22(s，1H，CH)，6.34(s，1H，C6H24-H)，6.55(s，1H，C6H26-H)，6.88～7.00(m，4H，C6H4)，7.40(s，1H，CCH), 7.55 (s, 1H, triazole ring 3-H), 7.61 (s, 1H, triazole ring 5-H); (Z)-B3:m.p.75～78 DEG C,1HNMR(400MHz，CDCl3)δ:1.33(s，6H，2×CH3)，2.90(s，2H，CH2)，3.96(s，3H，OCH3)，5.24(s，1H，CH)，6.35(s，1H，C6H24-H)，6.56(s，1H，C6H26-H)，7.35～7.40(m，4H，C6H4), 7.52 (s, 1H, CCH), 7.55 (s, 1H, triazole ring 3-H), 7.61 (s, 1H, triazole ring 5-H).
Embodiment 4
(Z/E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(2-chlorphenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B4 and (E)-B4]
Operation is with embodiment 1. Reaction 0.5h, yield 87.1%. (E)-B4:m.p.83～84 DEG C,1HNMR(400MHz，CDCl3)δ:1.46(s，6H，2×CH3)，2.94(s，2H，CH2)，3.78(s，3H，OCH3)，5.96(s，1H，CH)，6.67～6.80(m，2H，C6H24,6-H)，7.32(m，4H，C6H4)，7.07(s，1H，CCH)，8.01(s，1H, triazole ring 3-H), 8.49 (s, 1H, triazole ring 5-H); (Z)-B4:m.p.69～72 DEG C,1HNMR(400MHz，CDCl3)δ:1.49(s，6H，2×CH3)，2.98(s，2H，CH2)，3.84(s，3H，OCH3)，5.83(s，1H，CH)，6.68～6.74(m，2H，C6H24,6-H)，7.32～7.51(m，4H，C6H4)，7.40(s，1H，CCH)，8.00 (s, 1H, triazole ring 3-H), 8.24 (s, 1H, triazole ring 5-H).
Embodiment 5
(Z/E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-chlorphenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B5 and (E)-B5]
Operation is with embodiment 1. Reaction 0.5h, yield 76.7%. (E)-B5:m.p.78～81 DEG C,1HNMR(400MHz，CDCl3)δ:1.48(s，6H，2×CH3)，2.97(s，2H，CH2)，3.78(s，3H，OCH3)，5.08(br，1H，OH)，5.57(s，1H，CH)，6.62(s，1H，C6H24-H)，6.85(s，1H，C6H26-H)，6.85(d，J＝8.0Hz，2H，C6H43,5-H)，7.17(d，J＝8.0Hz，2H，C6H42,6-H)，7.58(s，1H，CCH)，8.01(s，1H, triazole ring 3-H), 8.20 (s, 1H, triazole ring 5-H); (Z)-B5:m.p.82～84 DEG C,1HNMR(400MHz，CDCl3)δ:1.50(s，6H，2×CH3)，3.00(s，2H，CH2)，3.81(s，3H，OCH3)，4.42(br，1H，OH)，5.03～5.04(m，1H，CH)，6.53(s，1H，C6H24-H)，6.63(s，1H，C6H26-H)，6.83(d，J＝8.0Hz，2H，C6H43,5-H)，7.16(d，J＝8.0Hz，2H，C6H42,6-H)，7.26(s，1H，CCH)，7.70 (s, 1H, triazole ring 3-H), 8.02 (s, 1H, triazole ring 5-H).
Embodiment 6
(Z/E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(2,4-dichlorophenyl)-2-(1,2,4-triazole-1-yl) preparation of-2-propylene-1-alcohol [(Z)-B6 and (E)-B6]
Operation is with embodiment 1. Reaction 0.5h, yield 76.7%. (E)-B6:m.p.72～75 DEG C,1HNMR(400MHz，CDCl3)δ:1.49(s，6H，2×CH3)，2.98(s，2H，CH2)，3.83(s，3H，OCH3)，5.68(s，1H，CH)，6.62～6.71(m，2H，C6H24,6-H)，6.75～7.42(m，3H，C6H3)，7.52(s，1H，CCH)，8.00 (s, 1H, triazole ring 3-H), 8.43 (s, 1H, triazole ring 5-H); (Z)-B6:m.p.84～87 DEG C,1HNMR(400MHz，CDCl3)δ:1.47(s，6H，2×CH3)，2.95(s，2H，CH2)，3.77(s，3H，OCH3)，5.84(s，1H，CH)，6.56～6.68(m，2H，C6H24,6-H)，7.15～7.77(m，3H，C6H3)，7.80(s，1H，CCH)，8.58 (s, 1H, triazole ring 3-H), 8.99 (s, 1H, triazole ring 5-H).
Embodiment 7
(Z/E)-1-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(3-nitrobenzophenone)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B7 and (E)-B7]
Operation is with embodiment 1. Reaction 0.5h, yield 84.9%. (E)-B7: liquid,1HNMR(400MHz，CDCl3)δ:1.35(s，6H，2×CH3)，2.50(s，2H，CH2)，3.64(s，3H，OCH3)，5.76(s，1H，CH)，6.00(br，1H，OH)，6.50(s，1H，C6H24-H)，6.61(s，1H，C6H26-H)，7.46～7.80(m，4H，C6H4), 7.96 (s, 1H, CCH), 8.02 (s, 1H, triazole ring 3-H), 8.48 (s, 1H, triazole ring 5-H); (Z)-B7:m.p.91～94℃，1HNMR(400MHz，CDCl3)δ:1.39(s，6H，2×CH3)，2.96(s，2H，CH2)，3.70(s，3H，OCH3)，4.82(s，1H，CH)，5.62(br，1H，OH)，6.67(s，1H，C6H24-H)，6.77(s，1H，C6H26-H)，7.45～7.90(m，4H，C6H4)，7.86(s，1H，CCH)，8.31(s，1H，Triazole ring 3-H).
Embodiment 8
(Z/E)-1-(7-ethyoxyl-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-aminomethyl phenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B8 and (E)-B8]
Operation is with embodiment 1. Reaction 0.5h, yield 80.0%. (E)-B8:m.p.57～60 DEG C,1HNMR(400MHz，CDCl3)δ:1.41(t，J＝8.0Hz，3H，CH3)，1.50(s，6H，2×CH3)，2.24(s，3H，CH3)，2.98(s，2H，CH2)，4.05(q，J＝8.0Hz，2H，CH2)，4.38～4.40(m，1H，OH)，5.09～5.10(m，1H，CH)，6.68～6.70(m，2H，C6H2)，6.72(d，J＝8.0Hz，2H，C6H42,6-H)，6.96(d，J＝8.0Hz，2H，C6H43,5-H), 7.45 (s, 1H, triazole ring 3-H), 7.94 (s, 1H, triazole ring 5-H); (Z)-B8:m.p.59～62℃，1HNMR(400MHz，CDCl3)δ:1.37(t，J＝8.0Hz，3H，CH3)，1.47(s，6H，2×CH3)，2.40(s，3H，CH3)，2.93(s，2H，CH2)，4.03(q，J＝8.0Hz，2H，CH2)，5.90(s， 1H，OH)，6.12(s，1H，CH)，6.62～6.64(m，2H，C6H2)，7.09～7.30(m，4H，C6H4)，7.96(s, 1H, triazole ring 3-H), 8.37 (s, 1H, triazole ring 5-H).
Embodiment 9
(Z/E)-1-(7-ethyoxyl-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(2-methoxyphenyl)-2-(1,2,4-triazole-1-yl) preparation of-2-propylene-1-alcohol [(Z)-B9 and (E)-B9]
Operation is with embodiment 1. Reaction 0.5h, yield 66.7%. (E)-B9:m.p.163～165 DEG C,1HNMR(400MHz，CDCl3)δ:1.37(t，J＝7.2Hz，3H，CH3)，1.47(s，6H，2×CH3)，2.94(s，2H，CH2)，3.89(s，3H，CH3)，4.12(q，J＝7.2Hz，2H，CH2)，6.01(s，1H，CH)，6.69(s，1H，C6H24-H)，6.74(s，1H，C6H26-H)，6.95～7.02(m，4H，C6H4)，7.31(s，1H，C＝CH)，7.97(s，1H，Triazole ring 3-H), 8.44 (s, 1H, triazole ring 5-H); (Z)-B9:m.p.165～168 DEG C,1HNMR(400MHz，CDCl3)δ:1.37(t，J＝7.2Hz，3H，CH3)，1.48(s，6H，2×CH3)，2.97(s，2H，CH2)，3.95(s，3H，CH3)，4.09(q，J＝7.2Hz，2H，CH2)，5.67(s，1H，CH)，6.58～6.79(m，2H，C6H2)，6.95～7.02(m，4H，C6H4), 7.39 (s, 1H, C=CH), 7.60 (s, 1H, triazole ring 3-H), 8.02 (s, 1H, triazole ring5-H)。
Embodiment 10
(Z/E)-1-(7-ethyoxyl-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-fluorophenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B10 and (E)-B10]
Operation is with embodiment 1. Reaction 0.5h, yield 60.0%. (E)-B10:m.p.48～51 DEG C,1HNMR(400MHz，CDCl3)δ:1.38(t，J＝7.2Hz，3H，CH3)，1.48(s，6H，2×CH3)，2.95(s，2H，CH2)，4.04(q，J＝7.2Hz，2H，CH2)，6.06(s，1H，CH)，6.66(s，1H，C6H2，4-H)，6.73(s，1H，C6H26-H)，7.09～7.41(m，4H，C6H4), 7.38 (s, 1H, C=CH), 7.98 (s, 1H, triazole ring 3-H),8.43 (s, 1H, triazole ring 5-H); (Z)-B10:m.p.40～43 DEG C,1HNMR(400MHz，CDCl3)δ:1.40(t，J＝7.2Hz，3H，CH3)，1.48(s，6H，2×CH3)，2.97(s，2H，CH2)，4.07(q，J＝7.2Hz，2H，CH2)，6.59(s，1H，CH)，6.65(s，1H，C6H24-H)，6.72(s，1H，C6H26-H)，7.09～7.41(m， 4H，C6H4), 7.24 (s, 1H, C=CH), 7.63 (s, 1H, triazole ring 3-H), 8.04 (s, 1H, triazole ring 5-H)
Embodiment 11
(E)-1-(7-ethyoxyl-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(2,4-dichlorophenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(E)-B11]
Operation is with embodiment 1. Reaction 0.5h, yield 87.5%. (E)-B11:m.p.63～65 DEG C,1HNMR(400MHz，CDCl3)δ:1.24～1.25(m，3H，CH3)，1.42(s，6H，2×CH3)，2.94(s，2H，CH2)，3.14～3.31(m，2H，CH2)，4.03(q，J＝7.6Hz，2H，CH2)，5.96(s，1H，CH)，6.71～7.03(m，2H，C6H2)，7.30～7.45(m，4H，C6H4), 7.52 (s, 1H, C=CH), 8.08 (s, 1H, triazole ring 3-H), 8.24(s, 1H, triazole ring 5-H).
Embodiment 12
(Z/E)-1-(7-ethyoxyl-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-bromophenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B12 and (E)-B12]
Operation is with embodiment 1. Reaction 0.5h, yield 72.7%. (E)-B12:m.p.65～69 DEG C,1HNMR(400MHz，CDCl3)δ:1.39(t，J＝8.0Hz，3H，CH3)，1.49(s，6H，2×CH3)，2.97(s，2H，CH2)，4.05(q，J＝8.0Hz，2H，CH2)，5.58(s，1H，OH)，6.05(s，1H，CH)，6.64～6.69(m，2H，C6H2)，6.70～6.84(m，2H，C6H43,5-H)，7.35(d，J＝8.0Hz，2H，C6H42,6-H)，7.54～7.56(m, 1H, CCH), 7.60 (s, 1H, triazole ring 3-H), 8.09 (s, 1H, triazole ring 5-H); (Z)-B12:m.p.81～85℃，1HNMR(400MHz，CDCl3)δ:1.41(t，J＝8.0Hz，3H，CH3)，1.50(s，6H，2×CH3)，2.99(s，2H，CH2)，4.08(q，J＝8.0Hz，2H，CH2)，4.43(s，1H，OH)，5.11(s，1H，CH)，6.67～6.71(m，2H，C6H2)，6.71～6.72(m，2H，C6H43,5-H)，7.28(d，J＝8.0Hz，2H，C6H42,6-H), 7.52～7.55 (m, 1H, CCH), 7.70 (s, 1H, triazole ring 3-H), 8.00 (s, 1H, triazole ring 5-H).
Embodiment 13
(Z/E)-1-(7-ethyoxyl-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-nitrobenzophenone)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B13 and (E)-B13]
Operation is with embodiment 1. Reaction 0.5h, receives 73.3%. (E)-B13:m.p.127～130 DEG C,1HNMR(400MHz，CDCl3)δ:1.41(t，J＝8.0Hz，3H，CH3)，1.49(s，6H，2×CH3)，2.98(s，2H，CH2)，4.05(q，J＝8.0Hz，2H，CH2)，5.63(s，1H，CH)，6.64(s，1H，C6H24-H)，6.72(s，1H，C6H26-H)，7.02(d，J＝8.0Hz，2H，C6H42,6-H)，7.44～7.60(m，2H，C6H43,5-H)，7.67(s，1H，CCH), 8.07 (s, 1H, triazole ring 3-H), 8.11 (s, 1H, triazole ring 5-H); (Z)-B13:m.p.55～58 DEG C,1HNMR(400MHz，CDCl3)δ:1.40～1.44(m，3H，CH3)，1.50(s，6H，2×CH3)，2.99(s，2H，CH2)，4.10～4.14(m，2H，CH2)，4.63(s，1H，OH)，5.15(s，1H，CH)，6.69～6.73(m，2H，C6H2)，7.00～7.34(m，4H，C6H4)，7.52～7.54(m，1H，CCH)，8.03～8.07(m，2H，Triazole ring 3,5-H).
Embodiment 14
(Z+E)-1-(7-propoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-aminomethyl phenyl)-2-(1,2,4-triazole-1-yl) preparation of-2-propylene-1-alcohol [B14]
Operation is with embodiment 1. Reaction 0.5h, yield 63.6%. B14:m.p.55～58 DEG C,1HNMR(400MHz，CDCl3)δ:0.92～0.95(m，3H，CH3)，1.36(s，6H，2×CH3)，1.61～1.67(m，2H，CH2)，2.92(s，2H，CH2)，3.80～3.86(m，2H，CH2)，4.70～4.75(m，1H，OH)，5.88～5.90(m，1H，CH)，6.48(s，1H，C6H24-H)，6.59(s，1H，C6H26-H)，6.85(d，J＝8.0Hz，2H，C6H42,6-H)，6.95(d，J＝8.0Hz，2H，C6H43,5-H), 7.26～7.27 (m, 1H, C=CH), 7.83 (s, 1H, triazole ring3-H), 7.93 (s, 1H, triazole ring 5-H).
Embodiment 15
(Z/E)-1-(7-propoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(2-methoxyphenyl)-2-(1,2,4-triazole-1-yl) preparation of-2-propylene-1-alcohol [(Z)-B15 and (E)-B15]
Operation is with embodiment 1. Reaction 0.5h, yield 81.8%. (E)-B15:m.p.152～155 DEG C,1HNMR(400MHz，CDCl3)δ:1.00(t，J＝7.2Hz，3H，CH3)，1.48(s，6H，2×CH3)，1.79～1.82(m，2H，CH2)，2.96(s，2H，CH2)，3.79(s，3H，OCH3)，3.94～3.99(t，J＝7.2Hz，2H，CH2)，4.58(s，1H，OH)，5.66(s，1H，CH)，6.58～6.75(m，2H，C6H2)，6.79～7.03(m，4H，C6H4)，7.23(s, 1H, C=CH), 7.71 (s, 1H, triazole ring 3-H), 8.04 (s, 1H, triazole ring 5-H); (Z)-B15:m.p.92～95℃，1HNMR(400MHz，CDCl3)δ:1.01(t，J＝7.6Hz，3H，CH3)，1.51(s，6H，2×CH3)，1.80～1.83(m，2H，CH2)，3.01(s，2H，CH2)，3.16～3.22(d，J＝7.2Hz，2H，CH2)，3.27(q，J＝7.2Hz，1H，CH)，3.27(d，J＝9.2Hz，2H，CH2)，3.70(s，3H，CH3)，3.98(t，J＝7.2Hz，2H，CH2)，4.78(m，1H，OH)，5.13～5.17(m，1H，CH)，6.69(s，2H，C6H2)，6.70～7.16(m，4H，C6H4), 7.52 (s, 1H, C=CH), 7.62 (s, 1H, triazole ring 3-H), 7.93 (s, 1H, triazole ring5-H)。
Embodiment 16
(Z/E)-1-(7-propoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-fluorophenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B16 and (E)-B16]
Operation is with embodiment 1. Reaction 0.5h, yield 88.2%. (E)-B16:m.p.54～56 DEG C,1HNMR(400MHz，CDCl3)δ:0.96(t，3H，J＝7.2Hz，CH3)，1.46(s，6H，2×CH3)，1.75～1.82(m，2H，CH2)，2.95(s，2H，CH2)，3.71～3.74(m，2H，CH2)，5.58(s，1H，OH)，6.11(s，1H，CH)，6.66～6.74(m，2H，C6H2)，6.82～7.40(m，4H，C6H4)，7.71(s，1H，CCH)，8.09(s，1H，Triazole ring 3-H), 8.65 (s, 1H, triazole ring 5-H); (Z)-B16:m.p.145～48 DEG C,1HNMR(400MHz，CDCl3)δ:1.02(t，3H，J＝7.2Hz，CH3)，1.50(s，6H，2×CH3)，1.80～1.83(m，2H，CH2)，2.99(s，2H，CH2)，3.97～3.99(m，2H，CH2)，4.61(s，1H，OH)，4.93～4.95(m，1H，CH)，6.69～6.72(m，2H，C6H2)，6.86～7.35(m，4H，C6H4), 7.75 (s, 1H, CCH), 8.15 (s, 1H, triazole ring3-H), 8.39 (s, 1H, triazole ring 5-H).
Embodiment 17
(Z/E)-1-(7-propoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(2-chlorphenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B17 and (E)-B17]
Operation is with embodiment 1. Reaction 0.5h, yield 75.0%. (E)-B17:m.p.56～59 DEG C,1HNMR(400MHz，CDCl3)δ:0.98(t，J＝7.2Hz，3H，CH3)，1.46(s，6H，2×CH3)，1.74～1.78(m，2H，CH2)，2.93(s，2H，CH2)，3.92(t，J＝7.2Hz，2H，CH2)，5.92(s，1H，OH)，6.67(s，2H，C6H2)，7.00～7.47(m，4H，C6H4), 7.49 (s, 1H, C=CH), 8.02 (s, 1H, triazole ring 3-H), 8.52 (s, 1H,Triazole ring 5-H); (Z)-B17:m.p.146～148 DEG C,1HNMR(400MHz，CDCl3)δ:1.02(t，J＝7.2Hz，3H，CH3)，1.51(s，6H，2×CH3)，1.80～1.85(m，2H，CH2)，2.99(s，2H，CH2)，3.99(t，J＝7.2Hz，2H，CH2)，4.82～4.83(m，1H，OH)，5.19(s，1H，CH)，6.74～6.77(m，2H，C6H2)，7.00～7.35(m，4H，C6H4), 7.52 (s, 1H, C=CH), 8.13 (s, 1H, triazole ring 3-H), 8.29(s, 1H, triazole ring 5-H).
Embodiment 18
(Z/E)-1-(7-propoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-chlorphenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B18 and (E)-B18]
Operation is with embodiment 1. Reaction 0.5h, yield 71.4%. (E)-B18:m.p.40～43 DEG C,1HNMR(400MHz，CDCl3)δ:1.01(t，3H，J＝7.2Hz，CH3)，1.50(s，6H，2×CH3)，1.78～1.82(m，2H，CH2)，2.99(s，2H，CH2)，3.92～3.97(m，2H，CH2)，5.11～5.12(m，1H，CH)，6.70～6.72(m，2H，C6H24,6-H)，6.81(d，J＝8.0Hz，2H，C6H42,6-H)，7.14(d，J＝8.0Hz，2H，C6H43,5-H)，7.20 (s, 1H, CCH), 8.04～8.25 (m, 2H, triazole ring); (Z)-B18:m.p.56～58 DEG C,1HNMR(400MHz，CDCl3)δ:1.10(t，3H，J＝7.2Hz，CH3)，1.49(s，6H，2×CH3)，1.78～1.84(m，2H，CH2)，2.99(s，2H，CH2)，3.93～4.00(m，2H，OCH2)，4.34～4.37(m，1H，OH)，5.09～5.10(m，1H，CH)，6.65～6.70(m，2H，C6H24,6-H)，6.72(d，J＝8.2Hz，2H，C6H42,6-H)，7.12(d，J＝8.2Hz，2H，C6H43,5-H), 7.45 (s, 1H, CCH), 7.97～8.10 (m, 2H, triazole ring).
Embodiment 19
(Z/E)-1-(7-propoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(2,4-chlorphenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B19 and (E)-B19]
Operation is with embodiment 1. Reaction 0.5h, yield 91.7%, m.p.65～69 DEG C, 1.01 (t, J=6.8Hz, 3H,CH3)，1.49(s，6H，2×CH3)，1.81(m，2H，CH2)，2.96(s，2H，CH2)，3.95～3.97(m，2H，CH2)，4.71(br，1H，OH)，5.01(m，1H，CH)，5.18(s，1H，C＝CH)，6.58～6.73(m，2H，C6H24-H)，7.18(s，1H，C6H26-H)，7.28～7.50(m，3H，C6H3), 8.07 (s, 1H, triazolesRing 3-H), 8.46 (s, 1H, triazole ring 5-H).
Embodiment 20
(Z/E)-1-(7-propoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-bromophenyl)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B20 and (E)-B20]
Operation is with embodiment 1. Reaction 0.5h, yield 66.7%. (E)-B20:m.p.135～137 DEG C,1HNMR(400MHz，CDCl3)δ:0.99(t，J＝7.2Hz，3H，CH3)，1.49(s，6H，2×CH3)，1.74～1.78(m，2H，CH2)，2.95～2.97(m，2H，CH2)，3.93(t，J＝7.2Hz，2H，CH2)，5.59(s，1H，OH)，6.12(s，1H，CH)，6.66(s，1H，C6H24-H)，6.70～6.73(m，2H，C6H43,5-H)，6.83(s，1H，C6H26-H)，7.36～7.37(m，2H，C6H42,6-H), 7.75 (s, 1H, C=CH), 8.12 (s, 1H, triazole ring 3-H), 8.78 (s,1H, triazole ring 5-H); (Z)-B20:m.p.55～58 DEG C,1HNMR(400MHz，CDCl3)δ:0.97(t，J＝7.2Hz，3H，CH3)，1.51(s，6H，2×CH3)，1.77～1.80(m，2H，CH2)，2.97(s，2H，CH2)，3.94(t，J＝7.2Hz，2H，CH2)，5.60(s，1H，OH)，6.18(s，1H，CH)，6.67～6.70(m，2H，C6H2)，6.78～6.83(m，2H，C6H42,6-H)，7.31～7.35(m，2H，C6H43,5-H)，7.56(s，1H，C＝CH)，8.01 (s, 1H, triazole ring 3-H), 8.05 (s, 1H, triazole ring 5-H).
Embodiment 21
(Z/E)-1-(7-propoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(2-nitrobenzophenone)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B21 and (E)-B21]
Operation is with embodiment 1. Reaction 0.5h, yield 65.2%. (E)-B21:m.p.123～126 DEG C,1HNMR(400MHz，CDCl3)δ:0.98(t，J＝7.2Hz，3H，CH3)，1.44(s，6H，2×CH3)，1.72～1.76(m，2H，CH2)，2.90(s，2H，CH2)，3.87(t，J＝7.2Hz，2H，CH2)，5.18(s，1H，OH)，5.75(s，1H，CH)，6.58～6.59(m，2H，C6H2)，7.54～8.06(m，4H，C6H4)，8.06(s，1H，CCH)，8.24～8.26(m，1H, triazole ring 3-H), 8.64 (s, 1H, triazole ring 5-H); (Z)-B21:m.p.56～58 DEG C,1HNMR(400MHz，CDCl3)δ:1.02(t，J＝7.2Hz，3H，CH3)，1.48(s，6H，2×CH3)，1.80～1.82(m，2H，CH2)，2.97(s，2H，CH2)，4.02(m，2H，CH2)，5.00(s，1H，OH)，5.20(m，1H，CH)，5.75(s，1H，C＝CH)，6.68～6.70(m，1H，C6H24-H)，6.80(m，1H，C6H26-H)，7.43～7.93(m，4H，C6H4), 7.98 (s, 1H, triazole ring 3-H), 8.11～8.13 (m, 1H, triazole ring 5-H).
Embodiment 22
(Z/E)-1-(7-propoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(3-nitrobenzophenone)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B22 and (E)-B22]
Operation is with embodiment 1. Reaction 0.5h, yield 84.6%. (E)-B22:m.p.95～98 DEG C,1HNMR(400MHz，CDCl3)δ:1.02(t，J＝7.2Hz，3H，CH3)，1.50(s，6H，2×CH3)，1.78～1.83(m，2H，CH2)，2.98(s，2H，CH2)，3.49(t，J＝7.2Hz，2H，CH2)，4.69(s，1H，OH)，5.12～5.13(m，1H，CH)，6.70(s，2H，C6H2)，7.20～8.02(m，4H，C6H4)，7.91(s，1H，C＝CH)，8.10(s，1H，Triazole ring 3-H), 8.30 (s, 1H, triazole ring 5-H); (Z)-B22:m.p.115～118 DEG C,1HNMR(400MHz，DMSO-d6)δ:0.96(t，J＝7.2Hz，3H，CH3)，1.39(s，6H，2×CH3)，1.68～1.70(m，2H，CH2)，2.96(s，2H，CH2)，3.86～3.88(m，2H，CH2)，4.80(s，1H，CH)，4.81～4.83(m，1H，OH)，5.59(m，1H，C＝CH)，6.69(s，1H，C6H24-H)，6.76(s，1H，C6H26-H)，7.43～7.84(m，4H，C6H4), 7.95 (s, 1H, triazole ring 3-H), 8.30 (s, 1H, triazole ring 5-H).
Embodiment 23
(Z/E)-1-(7-propoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-nitrobenzophenone)-2-(1,2,4-triazole-1-Base) preparation of-2-propylene-1-alcohol [(Z)-B23 and (E)-B23]
Operation is with embodiment 1. Reaction 0.5h, yield 92.3%. (E)-B23:m.p.134～137 DEG C,1HNMR(400MHz，CDCl3)δ:0.88(t，3H，J＝7.2Hz，CH3)，1.42(s，6H，2×CH3)，1.77～1.80(m，2H，CH2)，2.96～2.97(m，2H，CH2)，3.94(t，J＝7.2Hz，2H，CH2)，5.63(s，1H，OH)，6.06(s，1H，CH)，6.65(s，1H，C6H24-H)，6.71～6.74(m，1H，C6H26-H)，7.01(s，1H，C＝CH)，7.43～8.09(m，4H，C6H4), 8.11 (s, 1H, triazole ring 3-H), 8.28 (s, 1H, triazole ring 5-H); (Z)-B23:m.p.99～101℃，1HNMR(400MHz，CDCl3)δ:1.02(t，3H，J＝7.2Hz，CH3)，1.25(s，6H，2×CH3)，1.81～1.82(m，2H，CH2)，2.96(s，2H，CH2)，3.97(t，J＝7.2Hz，2H，CH2)，4.71(s，1H，OH)，5.14(s，1H，CH)，6.70(s，2H，C6H2)，7.11～8.04(m，4H，C6H4)，8.04～8.06(m，2H, triazole ring).
Embodiment 24
1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol active anticancer is measured
1. antitumor activity principle
Mtt assay biological activity test claims again MTT colorimetric method, is a kind of method that detects cell survival and growth. MTTAnalytic approach is with living cells metabolin reducing agent tetrazolium bromide [3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl bromination tetrazole;3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide, MTT] be basis. MTT is onePlant the dyestuff that can accept hydrogen atom. What in living cells mitochondria, the dehydrogenase relevant to NADP can be by yellow in cellMTT changes into insoluble hepatic first a ceremonial jade-ladle, used in libation (formazon), and dead cell is without this function. Dissolve with DMSOAfter formazon, under certain wavelength, measure OD value with ELIASA, both can quantitatively measure the survival rate of cell. According toThe inhibitory action of sample to tumour cell observed in the variation of OD value.
2. antitumor activity experiment
Sample: 1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol or its salt:
Wherein, R is selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl; X1、X5Be selected from: hydrogen,Deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl orBranched alkoxy, fluorine, chlorine, bromine or nitro; X3Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or side chainAlkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl or branched alkoxy, fluorine, chlorine, bromine or nitro; X2、X4Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, or nitro.
Clone: cervical cancer tumer line Hela, lung adenocarcinoma cell is that MCF-7 and breast cancer cell line MCF-7 are (Central-South largeXue Xiangya medical college cell bank provides).
Reagent: tetrazolium bromide (MTT), RPMI1640 nutrient solution, NBCS, antibiotic (U.S. hero life technologyCompany); Pancreatin (AMRESCO company of the U.S.); 96 well culture plates (hero Life Technologies, Inc. of the U.S.); Dimethyl sulfoxide (DMSO) (U.S.Sigma company of state).
Instrument: HFsafe-1500 type superclean bench, HF151UV type CO2(power Shen, Shanghai scientific instrument are limited for incubatorCompany); XSP-15C type inverted microscope (Shanghai rectangular optical instrument Co., Ltd); MultiskanMK3 type ELIASA (U.S.Thermo company of state); Ultra-pure water preparing instrument (Milli-Q company of the U.S.).
Experimental implementation: sample is for the test of cancer cell. In an experimentation, per sample (p.s.) arranges 5 concentration gradients(1.000 μ mol/mL, 0.300 μ mol/mL, 0.100 μ mol/mL, 0.030 μ mol/mL and 0.010 μ mol/mL), everyFour parallel samples of individual concentration, test parallel 3 times for every group, and reach a conclusion by the contrast of blank group. ELIASA detects eachHole OD value, detects wavelength 570nm.
3. antitumor activity evaluation
1) cell inhibitory rate calculates:
2)IC50Value is calculated
Sample solution concentration logarithm value and cell inhibitory rate linear regression, utilize software SPSS to calculate sample the half of cell suppressedConcentration IC50Value. The IC of 1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol to cancer cell50In table 1～2.
The IC of table 1 (Z)-1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol to cancer cell50
The IC of table 2 (E)-1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol to cancer cell50
1-(7-propoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-3-(4-aminomethyl phenyl)-2-(1,2,4-triazole-1-Base) IC of-2-propylene-1-alcohol to human cervical carcinoma cell (Hela) and human lung carcinoma cell (A549)50Be respectively 44.0 and 93.2μmol/L。
Test result show (Z/E)-1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol orIts salt has good pressing down to human cervical carcinoma cell (Hela), human lung carcinoma cell (A549) and human breast cancer cell (MCF-7) respectivelySystem is active, can be used as the application of preparing anticarcinogen.

Claims (6)

1. (benzofuran-5-yl)-3-phenyl-2-of the 1-shown in chemical structural formula I or II (1,2,4-triazol-1-yl)-2-propylene-1-alcohol or its salt:
Wherein, R is selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl; X1、X5Be selected from: hydrogen,Deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl orBranched alkoxy, fluorine, chlorine, bromine or nitro; X3Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or side chainAlkyl, hydroxyl, C1～C2Alkoxyl, C3～C4Straight chain alkoxyl or branched alkoxy, fluorine, chlorine, bromine or nitro; X2、X4Be selected from: hydrogen, deuterium, C1～C2Alkyl, C3～C4Straight chained alkyl or branched alkyl, or nitro; Its salt is selected from: hydrochloride,Hydrobromate, sulfate, nitrate, phosphate, mesylate, benzene sulfonate, tosilate, malate,Lactate, succinate or butene dioic acid salt.
2. 1-claimed in claim 1 (benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol,It is characterized in that the compound shown in preferred chemical structural formula III or IV:
X in formula1～X5Definition as claimed in claim 1.
3. 1-claimed in claim 1 (benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol,It is characterized in that the compound shown in preferred chemical structural formula V or VI:
X in formula1～X5Definition as claimed in claim 1.
4. 1-claimed in claim 1 (benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcohol,It is characterized in that the compound shown in preferred chemical structural formula VII or VIII:
X in formula1～X5Definition as claimed in claim 1.
5. 1-claimed in claim 1 (benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propylene-1-alcoholPreparation method, is characterized in that its preparation feedback is as follows:
R in formula, X1～X5Definition as claimed in claim 1.
6. (benzofuran-5-yl)-3-phenyl-2-of the 1-described in any one (1,2,4-triazol-1-yl)-2-in claim 1～4Propylene-1-alcohol or its salt are in the application of preparing in cancer therapy drug.
CN201410573025.0A 2014-10-24 2014-10-24 1- (benzofuran -5- bases) -3- phenyl -2- (1,2,4- triazol-1-yls) propenyls and its application Active CN105585563B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410573025.0A CN105585563B (en) 2014-10-24 2014-10-24 1- (benzofuran -5- bases) -3- phenyl -2- (1,2,4- triazol-1-yls) propenyls and its application

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410573025.0A CN105585563B (en) 2014-10-24 2014-10-24 1- (benzofuran -5- bases) -3- phenyl -2- (1,2,4- triazol-1-yls) propenyls and its application

Publications (2)

Publication Number Publication Date
CN105585563A true CN105585563A (en) 2016-05-18
CN105585563B CN105585563B (en) 2018-09-21

Family

ID=55925504

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410573025.0A Active CN105585563B (en) 2014-10-24 2014-10-24 1- (benzofuran -5- bases) -3- phenyl -2- (1,2,4- triazol-1-yls) propenyls and its application

Country Status (1)

Country Link
CN (1) CN105585563B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104557888A (en) * 2015-01-23 2015-04-29 邵阳学院 Application of furan phenol allyl alcohol derivative used as herbicide
CN105859697A (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-propenol and application thereof
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 (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10287634A (en) * 1997-04-11 1998-10-27 Otsuka Pharmaceut Co Ltd Benzene derivatives
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
US20090192220A1 (en) * 2007-11-19 2009-07-30 Ore Pharmaceuticals Inc. Treatment for solid tumors
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

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10287634A (en) * 1997-04-11 1998-10-27 Otsuka Pharmaceut Co Ltd Benzene derivatives
WO2008040057A1 (en) * 2006-10-04 2008-04-10 Bionomics Limited Novel benzofuran potassium channel blockers and uses thereof
US20090192220A1 (en) * 2007-11-19 2009-07-30 Ore Pharmaceuticals Inc. Treatment for solid tumors
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

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CAPORUSCIO, FABIANA，ET AL: "Structure-Based Design of Potent Aromatase Inhibitors by High-Throughput Docking", 《JOURNAL OF MEDICINAL CHEMISTRY》 *
NAGARAJU, M.，ET AL: "Synthesis and selective cytotoxic activity of novel hybrid chalcones against prostate cancer cells", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105859697A (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-propenol and application thereof
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
CN105859697B (en) * 2015-01-19 2018-05-04 湖南大学 1- benzofuranols ether -3- phenyl -2- (1,2,4- triazol-1-yls) -2- propenyls and its application
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
CN104557888A (en) * 2015-01-23 2015-04-29 邵阳学院 Application of furan phenol allyl alcohol derivative used as herbicide

Also Published As

Publication number Publication date
CN105585563B (en) 2018-09-21

Similar Documents

Publication Publication Date Title
CN102675303B (en) 4-alkyl-2-arylamino-5-(1,2,4-triazole-1-group) thiazole and application thereof to preparation of medicaments for resisting cancer
Yadav et al. Synthesis, crystal structure and antimicrobial potential of some fluorinated chalcone-1, 2, 3-triazole conjugates
Vujasinović et al. Synthesis and biological validation of novel pyrazole derivatives with anticancer activity guided by 3D-QSAR analysis
CN104334546B (en) Novel ring-substituted N-pyridinyl amides as kinase inhibitors
Rajitha et al. Synthesis and pharmacological evaluations of novel 2H-benzo [b][1, 4] oxazin-3 (4H)-one derivatives as a new class of anti-cancer agents
CN105585563A (en) 1-(benzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)propenol and application thereof
CN105585562B (en) 1- (benzofuran -5- bases) -3- aryl -2- (triazol-1-yl) propenone and its application as anticarcinogen
CN110343033B (en) Magnolol series derivatives, and preparation method and application thereof
CN109438365A (en) N- (3- ((4- trifluoromethyl) -2- pyrimidine radicals) aminophenyl) -2,6- difluorobenzenesulfonamide derivative
CN104370892B (en) 1-(7-Methoxvbenzofuran-5-base)-3-(2-methoxyphenyl)-2-(1,2,4-triazol-1-yl) propenyl
de Souza-Fagundes et al. Correlation of structural features of novel 1, 2, 3-triazoles with their neurotoxic and tumoricidal properties
CN102070556A (en) 5-benzyl-4-alkyl-2-aminothiazole as well as preparation and application of 5-benzyl-4-alkyl-2-aminothiazole
CN102603728A (en) 4-alkyl-2-aryl amino-5-(1,2,4-triazol-1-yl)thiazole and preparation method and application thereof
Eldeken et al. Synthesis, biological activities and molecular docking analysis of a novel series of 11H-indeno [1, 2-b] quinoxalin-11-one derivatives
Zhang et al. Novel sphingosine kinase 1 inhibitor suppresses growth of solid tumor and inhibits the lung metastasis of triple-negative breast cancer
CN105367564A (en) N-[4-phenyl-5-(1,2,4-triazole-1-yl)thiazole-2-yl]amide and preparation and application thereof
CN104327055B (en) 1-(benzofuran-5-base)-2-(1,2,4-triazol-1-yl) ketoxime ether-acylamide and preparation method and application
CN104292219B (en) 1-(cumarone-5-base)-2-(1,2,4-triazol-1-yl) ketoxime heterocycle methyl ether and the application as anticarcinogen thereof
Chauhan et al. An approach to regioselective synthesis of pyrazole and isoxazole derivatives and study of their antimicrobial effect
CN103467368B (en) Medical application of N-pyridine methyl/ methoxyl-2-phenoxyl amide
Srinivas et al. Synthesis and Anticancer activity of 1, 2, 4-oxadiazol linked benzimidazole derivatives
CN104387373B (en) 1-(7-propoxy benzofuran-5-group)-3-(2-methoxyl phenyl)-2-(1,2,4-triazole-1- group)acrylketone
Al Otaibi et al. The influence of ionic liquids on the Knoevenagel condensation of 1 H-pyrrole-2-carbaldehyde with phenyl acetonitriles–cytotoxic 3-substituted-(1 H-pyrrol-2-yl) acrylonitriles
CN104327056B (en) The preparation method of 1-(benzofuran-5-base)-2-(1,2,4-triazol-1-yl) ketoxime ether and application thereof
CN103980152A (en) Benzamide compound with antitumor activity as well as preparation method and application thereof

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant