CN103467452A - Benzamide compounds and application thereof - Google Patents

Benzamide compounds and application thereof Download PDF

Info

Publication number
CN103467452A
CN103467452A CN2013104136434A CN201310413643A CN103467452A CN 103467452 A CN103467452 A CN 103467452A CN 2013104136434 A CN2013104136434 A CN 2013104136434A CN 201310413643 A CN201310413643 A CN 201310413643A CN 103467452 A CN103467452 A CN 103467452A
Authority
CN
China
Prior art keywords
benzamide compound
compound
alkyl
haloalkyl
group
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
CN2013104136434A
Other languages
Chinese (zh)
Other versions
CN103467452B (en
Inventor
卢久富
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.)
Shaanxi University of Technology
Original Assignee
Shaanxi University of Technology
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 Shaanxi University of Technology filed Critical Shaanxi University of Technology
Priority to CN201310413643.4A priority Critical patent/CN103467452B/en
Publication of CN103467452A publication Critical patent/CN103467452A/en
Application granted granted Critical
Publication of CN103467452B publication Critical patent/CN103467452B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Landscapes

  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention belongs to the technical field of medicines, and particularly relates to novel benzamide compounds which can be applied to medicines and form salts by adding acid. The pharmacological activity screening results of part of compounds show that the novel benzamide compound has a very good inhibiting effect on MCF-7 (human breast cancer cells) and HeLa (human cervical cancer cells) and good development and application prospects in the terms of resisting tumors.

Description

A kind of benzamide compound and application thereof
Technical field:
The invention provides a series antineoplastic medicament structure, belong to medical technical field.
Background technology:
One of public health problem that malignant tumour is larger as the whole world, the health of harm humans greatly, and will become the first killer of the new millennium mankind.From world wide, global new cases of cancer 1,010 ten thousand in 2000, dead 6,200,000, existing cancer stricken case 2,240 ten thousand, pathogenesis of cancer number in 2008 and death toll rise to respectively 1,266 ten thousand and 7,560,000, and estimating 2015 will have 15,000,000 new cases.Simultaneously, malignant tumour is the serious disease of advanced industrial country no longer just, and developing country is faced with larger disease burden.Within 2008, Incidence number developing country accounts for 56%; The cancer patients of 2009 80% concentrates on middle and low income country, and by 2015, developing country estimated at 9,000,000 people and dies from cancer.China is as a developing power, due to the quickening of industrialization, urbanization and aging population process, and the existence of the problems such as bad mode of life and environmental pollution, the situation that malignant tumour faces is also more severe.The invention provides a kind of anti-tumor activity benzamides medicines structure that has, there is important development prospect.
Summary of the invention:
The object of the present invention is to provide the new benzamides compounds, this compounds pharmacologically active result shows that it has good restraining effect to tumor cell line.
A kind of benzamide compound, is characterized in that, its structural formula is as shown in general formula (1):
Figure BDA0000380417250000011
Wherein:
R 1and R 2be selected from hydrogen, halogen, cyano group, hydroxyl, haloalkyl, alkoxyl group, alkoxyalkyl, alkylamino radical or alkylamino radical alkyl; Described haloalkyl is be selected from the cyclic saturated hydrocarbon of 3～10 saturated carbon atoms formation or have the straight or branched saturated hydrocarbyl that 1～10 saturated carbon Sauerstoffatom forms, and halogen is fluorine, chlorine, the substituting group of bromine or iodine.R 3and R 4be selected from alkyl, the phenyl of phenyl or replacement.
Described haloalkyl is be selected from the cyclic saturated hydrocarbon of 3～6 saturated carbon atoms formation or have the straight or branched saturated hydrocarbyl that 1～6 saturated carbon atom forms.
Described R 3and R 4form following radicals together with the N connected with them: imidazolidyl, 2-imidazolidyl, 3-imidazolidyl, pyrryl, the 2H-pyrryl, 2-pyrrolinyl, pyrrolidyl, triazolyl, pyrazolyl, piperazinyl, pyridazinyl, pyrazinyl, triazinyl, morpholinyl, thio-morpholinyl, described group can be optionally by hydroxyl, halogen, alkyl, amino, haloalkyl, alkylthio alkyl, alkoxyalkyl, pyrimidyl replace or group as follows
Figure BDA0000380417250000021
wherein Y is S, O, NH or N-alkyl; R 1and R 2can be identical or different.
Described benzamide compound can be used for antitumor drug;
The application of foregoing benzamide compound in antitumor monomer medicine or pharmaceutical composition.
A kind of pharmaceutical composition, is characterized in that comprising foregoing benzamide compound.
One or more pharmaceutical carriers or vehicle, is characterized in that comprising foregoing benzamide compound.
The closing of this compound be take 2-(2-amino-5-(dimethylamino) phenyl)-N-(3-(trifluoromethyl) phenyl) Isonicotinamide and made as starting raw material route via I, and concrete synthetic route is as follows:
Figure BDA0000380417250000022
According to above-mentioned route of synthesis, can obtain the medicine of following structure:
Figure BDA0000380417250000031
Said medicine can add one or more pharmaceutical carriers or vehicle, is prepared into tablet, capsule, powder, pill, granule or emulsion.Show that by pharmacological activity test it has good restraining effect to tumor cell line.
Description of drawings
Fig. 1 is compound (1) H NMR collection of illustrative plates;
Fig. 2 is compound (2) H NMR collection of illustrative plates;
Fig. 3 is compound (3) H NMR collection of illustrative plates;
Fig. 4 is compound (4) H NMR collection of illustrative plates;
Fig. 5 is compound (5) H NMR collection of illustrative plates;
Fig. 6 is compound (6) H NMR collection of illustrative plates;
Fig. 7 is compound (7) H NMR collection of illustrative plates;
Fig. 8 is compound (8) H NMR collection of illustrative plates.
Embodiment:
The present invention will be contributed to understand by following example, but content of the present invention can not be limited to.
Embodiment 1: compound (1) synthetic
Figure BDA0000380417250000041
Adopt the mode of synthetic route I:
By 2-(2-amino-5-(dimethylamino) phenyl)-N-(3-(trifluoromethyl) phenyl) Isonicotinamide (4.42g, 10mmol) with the 20mL methylene dichloride, be dissolved in the 100mL round-bottomed flask, add again triethylamine (5.05g, 50mmol), frozen water is cooled to-20 ℃.Simultaneously by 3-(chloromethyl) Benzoyl chloride (2.27g, 12mmol) be dissolved in the methylene dichloride of 30mL, and it is slowly splashed in above-mentioned round-bottomed flask, time for adding is 25min, control temperature at-20～-30 ℃, drip and finish the rear stirring 2h that continues, then naturally rise to stirred overnight at room temperature, reaction is finished.With pure water 50mL * 3 washing reaction liquid; anhydrous sodium sulfate drying; the concentrating under reduced pressure organic phase; finally adopt the silica gel column chromatography separate mode to be purified; eluent is that petrol ether/ethyl acetate=3:1 obtains easily niacinamide 4.90g of brown oil 2-(2-(3-(chloromethyl) benzoyl)-5-(dimethylamino) phenyl)-N-(3-(trifluoromethyl) phenyl); productive rate 82.41%, (ES, m/z): 595.2[M+H] + 1, 597.2[M+H+2] + 1.
Above-mentioned brown oil is dissolved in and contains N, in the round-bottomed flask of dinethylformamide 50mL, add respectively again sodium hydride 200mg, 5mmol, 2.00N, 60% and 4-(2, 5, 8, 11, 14, 17, 20, the hot oxo penta-25 of 23-)-1H-indoles 4.94g, 2.9.88mmol, 1.2N, whole system stirs 2h at ambient temperature, add ethyl acetate 100mL dilution, use again saturated aqueous common salt 100mL * 2 extractions, anhydrous sodium sulfate drying, the concentrating under reduced pressure organic phase, finally adopt silica gel column chromatogram separating purification, eluent is petrol ether/ethyl acetate=3:1, obtain brown oily product (1) 14.17g, productive rate 47.82%, (ES, m/z): 1058.2[M+H] + 1, 1010.2[M+H+2] + 1.H?NMR(300MHz,CD 3OD)δ:8.85(s,1H),8.33(s,1H),8.18(s,J=5.4,1H),7.91(s,2H),7.54～7.73(m,9H),7.25(s,1H),6.99～7.07(m,2H),6.68(d,J=2.7,1H),6.59(d,J=7.2,1H),5.50(s,2H),4.72(s,2H),4.28(s,2H),3.93(s,2H),3.50～3.75(m,35H),1.31(s,2H)，1.20～1.25(m,6H)。See Fig. 1.
Adopting suitable raw material and reagent, is synthetic route I according to the synthetic method of embodiment 1, can make new benzamides compounds in embodiment 2～8.
Embodiment 2: compound (2) synthetic
Figure BDA0000380417250000051
(ES,m/z):1036.2[M+H] +1，1038.2[M+H+2] +1;H?NMR(300MHz,CDCl 3)δ:8.87～8.97(m,2H),8.46(s,1H),8.17(s,1H),7.91～8.00(m,3H),7.84(s,2H),7.49～7.68(m,10H),4.72(s,2H),3.73～3.80(m,5H),3.47～3.61(m,23H),3.33(d,J=1.2,1H),2.81～2.86(m,2H),2.43～2.47(m,2H),1.92～1.97(m,2H),1.21～1.26(m,6H)。See Fig. 2.
Embodiment 3: compound (3) synthetic
(ES,m/z):974.2[M+H] +1，976.2[M+H+2] +1;H?NMR(300MHz,CDCl 3)δ:8.98(d,J=5.1,1H),8.83(d,J=8.7,1H),8.43(s,1H),8.06(s,1H),7.92(d,J=5.1,1H),7.81～7.84(m,2H),7.50～7.72(m,7H),4.72(s,2H),3.70～3.77(m,5H),3.51～3.63(m,21H),3.22(s,3H),2.82～2.87(m,2H),2.52～2.56(m,2H),1.57～2.00(m,8H),1.24～1.41(m,9H)。See Fig. 3.
Embodiment 4: compound (4) synthetic
Figure BDA0000380417250000053
(ES,m/z):924.2[M+H] +1，926.2[M+H+2] +1;H?NMR(300MHz,CDCl 3)δ:14.03(s,1H),13.68(s,1H),9.50(s,1H),9.35(s,1H),9.18(d,J=8.7Hz,1H),8.92(s,1H),8.35(d,J=3.9Hz,1H),8.01～7.92(m,3H),7.74～7.66(m,2H),7.53～7.43(m,3H),7.53～7.43(m,3H),7.38～7.30(m,2H),7.18～7.13(m,3H),7.00(d,J=6.3Hz,1H),6.68(d,J=2.4Hz,1H),5.45(s,2H),4.76(d,J=5.1Hz,2H),3.70～3.64(m,16H),3.57～3.53(m,5H),3.40(s,5H),3.02(t,J=7.2Hz,2H),2.83(s,1H),2.07(t,J=6.9Hz,2H),1.29(t,J=6.0Hz,2H)。See Fig. 4.
Embodiment 5: compound (5) synthetic
Figure BDA0000380417250000061
(ES,m/z):1012.2[M+H] +1，1014.2[M+H+2] +1;H?NMR(300MHz,CDCl 3)δ:8.82(d,J=6.6Hz,1H),8.42(s,1H),8.24(d,J=11.1Hz,2H),8.04(s,1H),7.90(d,J=4.2Hz,1H),7.80～7.69(m,4H),7.66～7.49(m,6H),7.41(d,J=7.8Hz,1H),7.33(d,J=3.0Hz,1H),7.22(d,J=8.4Hz,1H),7.09(t,J=6.3Hz,1H),6.93(d,J=7.2Hz,1H),6.65(d,J=3.0Hz,1H),5.51(d,J=3.3Hz,2H),4.71(s,2H),4.71(s,2H),3.73(d,J=7.2Hz,4H),3.66～3.46(m,29H),2.98(t,J=7.5Hz,2H),1.98(t,J=7.2Hz,2H),1.22(t,J=3.9Hz,6H)。See Fig. 5.
Embodiment 6: compound (6) synthetic
Figure BDA0000380417250000062
(ES,m/z):1101.2[M+H] +1，1103.2[M+H+2] +1;HNMR(300MHz,CDCl 3)δ:8.73(d,J=9.6Hz,1H),8.37(s,1H),8.27(s,1H),8.04(s,1H),7.90(d,J=4.2Hz,1H),7.80～7.69(m,4H),7.66～7.49(m,6H),7.41(d,J=7.8Hz,1H),7.33(d,J=3.0Hz,1H),7.22(d,J=8.4Hz,1H),7.09(t,J=6.3Hz,1H),6.93(d,J=7.2Hz,1H),6.65(d,J=3.0Hz,1H),5.51(d,J=3.3Hz,2H),4.71(s,2H),3.72(d,J=7.2Hz,4H),3.66～3.46(m,28H),2.98(t,J=7.5Hz,2H),1.98(t,J=7.2Hz,2H),1.20(t,J=3.9Hz,6H)。See Fig. 6.
Embodiment 7: compound (7) synthetic
(ES,m/z):1026.2[M+H] +1，1028.2[M+H+2] +1;H?NMR(300MHz,CDCl 3)δ:8.76(d,J=9.0Hz,1H),8.35(s,1H),8.24(d,J=5.1Hz,1H),8.03(s,1H),7.90(d,J=7.2Hz,1H),7.72～7.66(m,4H),7.63～7.53(m,5H),7.34(d,J=3.3Hz,1H),7.22(d,J=8.1Hz,1H),7.09(t,J=6.3Hz,1H),6.93(d,J=7.2Hz,1H),6.65(d,J=3.0Hz,1H),5.52(s,2H),4.71(s,2H),3.78～3.66(m,6H),3.63～3.58(m,10H),3.56～3.53(m,10H),3.49～3.34(m,2H),2.98(t,J=7.5Hz,2H),2.51(t,J=6.0Hz,2H),1.97(t,J=7.5Hz,2H),1.20(t,J=7.2Hz,6H)。See Fig. 7.
Embodiment 8: compound (8) synthetic
Figure BDA0000380417250000072
(ES,m/z):1159.2[M+H] +1，11597.2[M+H+2] +1;H?NMR(300MHz,CDCl 3)δ:8.78(d,J=9.0Hz,1H),8.37(s,1H),8.25(d,J=5.1Hz,1H),8.14(s,1H),7.88(d,J=7.2Hz,1H),7.72(m,1H),7.65(m,4H),7.61(m,1H),;7.48(m,5H),7.30(d,J=3.0Hz,1H),7.20(d,J=8.1Hz,1H),7.06(t,J=7.8Hz,1H),6.90(d,J=6.9Hz,1H),6.63(d,J=3.0Hz,1H),5.48(s,2H),4.70(s,2H),3.75(m,1H),3.68(m,6H),3.61(m,1H),3.51(m,30H),3.47(m,1H),3.43(m,2H),2.95(t,J=7.5Hz,2H),2.53(t,J=6.3Hz,2H),1.96(t,J=7.2Hz,2H),1.20(t,J=7.2Hz,6H)。See Fig. 8.
Embodiment 6: the compound pharmacological evaluation
Testing compound as research object, adopts tetramethyl-azo azoles salt colorimetry, i.e. mtt assay to MCF-7 (human breast cancer cell) and HeLa (human cervical carcinoma cell) tumour cell.Active in half-inhibition concentration (IC 50) mean, unit is μ M.
Take the MCF-7 cell as example:
Get the MCF-7 cell of 0.25% tryptic digestion monolayer culture, with the RPMI1640 nutrient solution containing 10% foetal calf serum, be made into single cell suspension, be inoculated in 96 orifice plates, every hole 200 μ L(are containing 3 * 10 4～5 * 10 4individual cell).Culture plate is put into to the CO2 incubator, at 37 ℃, 5%CO 2under condition, add the testing compound of different concns after culturing cell is adherent, 4 concentration (1 * 10 of each compound test -5, 1 * 10 -6, 1 * 10 -7, 1 * 10 -8mol/L), control group adds and the isopyknic solvent of administration group.Continuation is at CO 2in incubator in 37 ℃, 5%CO 2cultivate 72h under condition.Every hole adds 20 μ LMTT solution (5mg/mL), continue to hatch 4h in 37 ℃, end to cultivate, discard culture supernatant in hole, every hole adds 150 μ LDMSO, gentle agitation 10min, select the 570nm wavelength, measure each hole absorbance value (OD value) on microplate reader, the inhibiting rate with following formula computerized compound to tumour cell, and calculate IC 50.Repeated test 3 times, average as net result.
Figure BDA0000380417250000081
Compound MCF-7(IC 50μM) HeLa(IC 50μM)
(1) 4.28 7.21
(2) 14.63 ＞100
(3) 19.44 ＞100
(4) 8.25 10.09
(5) 7.55 7.38
(6) 6.28 9.41
(7) 10.48 13.56
(8) 10.55 12.16
Known by above-mentioned data, it is active that 1 couple of MCF-7 of compound and HeLa tumour cell have obvious inhibition, and the value of further research is arranged; Compound 2 and 3 pairs of MCF-7 tumour cells have all shown that weak inhibition is alive, to almost unrestraint activity of HeLa tumour cell; Compound 8 and 10 pairs of two kinds of tumour cells have shown poor inhibition activity; All the other compounds have also shown different inhibition activity to two kinds of tumour cells.Show on pyrazole ring-NR of Structure-activity Relationship 3r 4for indole structure is the anti-tumor activity that is conducive to improve compound, but be connected into again alkylsulfonyl or carboxyl likely reduces its anti-tumor activity when it.
Should be understood that, for those of ordinary skills, can be improved according to the above description or convert, and all these improvement and conversion all should belong to the protection domain of claims of the present invention.

Claims (7)

1. a benzamide compound, is characterized in that, its structural formula is as shown in general formula (1):
Wherein:
R 1and R 2be selected from hydrogen, halogen, cyano group, hydroxyl, haloalkyl, alkoxyl group, alkoxyalkyl, alkylamino radical or alkylamino radical alkyl; Described haloalkyl is be selected from the cyclic saturated hydrocarbon of 3～10 saturated carbon atoms formation or have the straight or branched saturated hydrocarbyl that 1～10 saturated carbon Sauerstoffatom forms, and halogen is fluorine, chlorine, the substituting group of bromine or iodine.R 3and R 4be selected from alkyl, the phenyl of phenyl or replacement.
2. benzamide compound as claimed in claim 1, is characterized in that, described haloalkyl is be selected from the cyclic saturated hydrocarbon of 3～6 saturated carbon atoms formation or have the straight or branched saturated hydrocarbyl that 1～6 saturated carbon atom forms.
3. benzamide compound as claimed in claim 1, is characterized in that, described R 3and R 4form following radicals together with the N connected with them: imidazolidyl, 2-imidazolidyl, 3-imidazolidyl, pyrryl, the 2H-pyrryl, 2-pyrrolinyl, pyrrolidyl, triazolyl, pyrazolyl, piperazinyl, pyridazinyl, pyrazinyl, triazinyl, morpholinyl, thio-morpholinyl, described group can be optionally by hydroxyl, halogen, alkyl, amino, haloalkyl, alkylthio alkyl, alkoxyalkyl, pyrimidyl replace or group as follows wherein Y is S, O, NH or N-alkyl; R 1and R 2can be identical or different.
4. benzamide compound as claimed in claim 1, is characterized in that described benzamide compound can be used for antitumor drug.
5. the application of the described benzamide compound of claim 1-3 in antitumor monomer medicine or pharmaceutical composition.
6. a pharmaceutical composition, is characterized in that comprising the benzamide compound described in claim 1-3.
7. one or more pharmaceutical carriers or vehicle, is characterized in that comprising the benzamide compound described in claim 1-3.
CN201310413643.4A 2013-09-11 2013-09-11 A kind of benzamide compound and application thereof Expired - Fee Related CN103467452B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201310413643.4A CN103467452B (en) 2013-09-11 2013-09-11 A kind of benzamide compound and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201310413643.4A CN103467452B (en) 2013-09-11 2013-09-11 A kind of benzamide compound and application thereof

Publications (2)

Publication Number Publication Date
CN103467452A true CN103467452A (en) 2013-12-25
CN103467452B CN103467452B (en) 2015-11-18

Family

ID=49792528

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201310413643.4A Expired - Fee Related CN103467452B (en) 2013-09-11 2013-09-11 A kind of benzamide compound and application thereof

Country Status (1)

Country Link
CN (1) CN103467452B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103772262A (en) * 2014-02-24 2014-05-07 陕西理工学院 Isophthalamide compounds having anti-tumor activity and application thereof
CN108997176A (en) * 2018-07-27 2018-12-14 温州医科大学 A kind of chloro- N- substituted-phenyl -3- sulphonamidobenzamide class compound of 4- and its preparation and antitumor application thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003057225A2 (en) * 2001-12-26 2003-07-17 Genzyme Corporation Phosphate transport inhibitors
WO2012006475A1 (en) * 2010-07-07 2012-01-12 Ardelyx, Inc. Compounds and methods for inhibiting phosphate transport
WO2012054110A2 (en) * 2010-07-07 2012-04-26 Ardelyx, Inc. Compounds and methods for inhibiting phosphate transport

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003057225A2 (en) * 2001-12-26 2003-07-17 Genzyme Corporation Phosphate transport inhibitors
WO2012006475A1 (en) * 2010-07-07 2012-01-12 Ardelyx, Inc. Compounds and methods for inhibiting phosphate transport
WO2012054110A2 (en) * 2010-07-07 2012-04-26 Ardelyx, Inc. Compounds and methods for inhibiting phosphate transport

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103772262A (en) * 2014-02-24 2014-05-07 陕西理工学院 Isophthalamide compounds having anti-tumor activity and application thereof
CN103772262B (en) * 2014-02-24 2015-10-14 陕西理工学院 A kind of different phthalimide derivatives and application thereof with anti-tumor activity
CN108997176A (en) * 2018-07-27 2018-12-14 温州医科大学 A kind of chloro- N- substituted-phenyl -3- sulphonamidobenzamide class compound of 4- and its preparation and antitumor application thereof
CN108997176B (en) * 2018-07-27 2021-07-02 温州医科大学 4-chloro-N-substituted phenyl-3-sulfonyl aminobenzamide compound, and preparation and anti-tumor application thereof

Also Published As

Publication number Publication date
CN103467452B (en) 2015-11-18

Similar Documents

Publication Publication Date Title
CN103702561B (en) Opioid receptor ligands and methods of using and making same
CN102295635B (en) Antitumor medicament tetralin amide compounds and pharmaceutically acceptable salts thereof as well as preparation method and application of antitumor medicament tetralin amide compounds
Patel et al. Novel imidazopyrimidines-based molecules induce tetramerization of tumor pyruvate kinase M2 and exhibit potent antiproliferative profile
CN105985342A (en) Pyrimido pyrimidine dione derivative as EGFR inhibitor and application thereof
AU2013318672B2 (en) Means and method for treating solid tumours
CN109867675A (en) Compound derived from a kind of pyrrolopyrimidine, pharmaceutical composition with and application thereof
CN103467452B (en) A kind of benzamide compound and application thereof
CN104829613B (en) Diaryl-substituted pyrazolo ring derivative, preparation method thereof and application thereof in medical field
CN103145706A (en) Imidazopyridine compound with anti-inflammatory action and application thereof to preparation of anti-inflammatory medicament
CN104892580B (en) A kind of novel benzimidazole pyrimidinamine derivatives and its application
EP2832726A1 (en) (2-heteroarylamino)succinic acid derivative
CN104725372A (en) Tetracyclic indole alkaloid derivative as well as preparation method and application thereof
CN106986854B (en) A kind of bisabolane sequiterpene analogue and the preparation method and application thereof
KR102606167B1 (en) Fluorine-containing substituted benzothiophene compounds, pharmaceutical compositions and applications thereof
CN105541696B (en) A kind of antitumor compound and its preparation method and application
CN104327083A (en) Substituted-indanyl amide-type compounds and pharmaceutically acceptable salt and preparation method and application thereof
CN104311539B (en) A kind of acridine acylhydrazone and its production and use
CN103396400A (en) Pyrazole amide compounds, and preparation method and application thereof
CN103145739A (en) Pyrimido thiazole type compounds with anti-inflammatory effect and application thereof in preparation of anti-inflammatory medicaments
CN104177289B (en) Chlorine hexyloxyethoxy ethyl compound and its pharmaceutical composition and purposes
CN103833651B (en) Weary oxygen selective anti-tumor predrug indenes (1,2-b) quinoxaline-5,10-dioxy-11-ketoxime ether derivative
CN103755652B (en) A kind of sulfamide compound and application thereof
CN103739615B (en) A kind of ketone compounds and application thereof with anti-tumor activity
CN104402818B (en) A kind of compound or pharmaceutically acceptable salt thereof with tumour response release medicine and preparation, application
CN103910718B (en) Double cyclosubstituted pyrazolone azo compounds, preparation method and use

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20151118

Termination date: 20160911

CF01 Termination of patent right due to non-payment of annual fee