CN102786458A - Pyrrole formamide derivative, and preparation method and application thereof - Google Patents
Pyrrole formamide derivative, and preparation method and application thereof Download PDFInfo
- Publication number
- CN102786458A CN102786458A CN2012101797892A CN201210179789A CN102786458A CN 102786458 A CN102786458 A CN 102786458A CN 2012101797892 A CN2012101797892 A CN 2012101797892A CN 201210179789 A CN201210179789 A CN 201210179789A CN 102786458 A CN102786458 A CN 102786458A
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- Prior art keywords
- compound
- pyrrole
- ethanoyl
- cyclopropyl
- dimethyl
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- MBMVDJPJUUQRTC-UHFFFAOYSA-N formamide 1H-pyrrole Chemical class N1C=CC=C1.C(=O)N MBMVDJPJUUQRTC-UHFFFAOYSA-N 0.000 title 1
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 235000020985 whole grains Nutrition 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to compounds with a structure shown as a formula I or pharmaceutically acceptable salts thereof. R1, R2, R3, R4, R5 and R6 are defined as in the specification. The invention also provides a preparation method of the compounds with a structure shown as the formula I or pharmaceutically acceptable salts thereof, pharmaceutical compositions containing the compounds and pharmaceutically acceptable salts thereof, and application of betulinic acid analogues or solvates thereof as active ingredients to preparation of antineoplastic medicaments for treating lung cancer, prostate cancer, colon cancer, leukemia, breast cancer, liver cancer, gastric cancer, pancreatic cancer, human malignant glioma and brain tumor.
Description
Technical field
The invention belongs to medical technical field, or rather, relate to one type of compound with antitumor action.
Background technology
Cancer has become a big chronic disease of serious harm human health at present.The annual in the world according to statistics people who suffers from cancer has 9,000,000, and the patient who dies from cancer is 6,000,000, and cancer patients's death is almost just arranged p.s..China's cancer year number of the infected is about 1,200,000, and the number of dying from cancer is up to more than 900,000, and patient to be treated surpasses 1,500,000, and the trend that rises is year by year arranged.Therefore cancer has become the second largest killer who is only second to cardiovascular disorder at present.Treat tumour clinically, generally adopt operation, radiotherapy, chemotherapy three big therapies.Though embolic chemotherapy is comparatively quick, curative ratio is very low.The many cancer therapy drugs of clinical discovery exist tangible damage and toxic side effect to normal body, for example mutagenesis and genetoxic simultaneously.Therefore, seek effectively and cancer therapy drug with less body injury and toxic side effect has become the focus of new drug research.
Summary of the invention
One object of the present invention is, discloses the pyrroyl sulfonamide derivatives and the pharmaceutical salts thereof of one type of novel texture.
Another object of the present invention is, discloses the preparation method of one type of pyrroyl sulfonamide derivatives and pharmaceutical salts thereof.
A further object of the present invention is, openly contains the pyrroyl sulfonamide derivatives and pharmaceutical salts is the pharmaceutical composition of main active ingredient with one type.
A further object of the invention is, discloses one type of application that contains pyrroyl sulfonamide derivatives and pharmaceutical salts thereof as medicine for resisting malignant tumors, particularly in the purposes that is used to prepare aspect treatment mammary cancer, lung cancer, the cancer of the stomach medicine.
Combine the object of the invention at present, content of the present invention is set forth in detail.
The present invention is specifically related to the compound and the pharmacy acceptable salt thereof of formula I structure:
Wherein:
R
1, R
2, R
3, R
4For: C
1-C
6The straight or branched alkyl, C
3-C
6Naphthenic base;
R
5, R
6Be at the same time or separately: hydrogen, C
1-C
6Alkyl; Hydroxyl, halogen, C
1-C
4Alkoxyl group, the substituted C of itrate group
1-C
6Alkyl.
Preferred following compound and pharmacy acceptable salt thereof:
Wherein:
R
1, R
2, R
3, R
4For: methyl, ethyl, propyl group, sec.-propyl, cyclopropyl;
R
5, R
6Be at the same time or separately: hydrogen, chloroethyl, chloropropyl, hydroxyethyl, hydroxypropyl, alkoxyl oxygen alkyl ethyl, itrate group ethyl.
More preferably following its pharmacy acceptable salt of compound:
I-1.4-ethanoyl-N, N-two (2-chloroethyl)-1-cyclopropyl-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-2.4-ethanoyl-1-cyclopropyl-N, N-two (2-hydroxyethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-3.4-ethanoyl-1-cyclopropyl-N, N-two (2-methoxyethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-4.4-ethanoyl-N-(2-chloroethyl)-1-cyclopropyl-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-5.4-ethanoyl-1-cyclopropyl-N-(2-hydroxyethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-6.4-ethanoyl-1-cyclopropyl-N, N-two (2-itrate group ethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-7.4-ethanoyl-1-cyclopropyl-N-(2-itrate group ethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide
Formula I compound pharmacy acceptable salt refers to: compound and mineral acid, organic acid salify.Wherein preferred: hydrochloride, hydrobromate, hydriodate, vitriol, hydrosulfate, phosphoric acid salt, acetate, propionic salt, butyrates, lactic acid salt, mesylate, tosilate, PHENRAMINE MALEATE, benzoate, SUMATRIPTAN SUCCINATE, tartrate, Citrate trianion, fumarate, taurate, gluconate, amino acid salts.
The preparation route of formula I compound is following:
R
1, R
2, R
3, R
4, R
5, R
6Definition as previously mentioned.
Substituted 1H-pyrroles-3-formic acid (II) generates intermediate III with thionyl chloride reaction, intermediate III and substituted aminated compounds under the catalysis of acid binding agent ,-10～50 ℃ of reacting generating compound I.
Substituted 1H-pyrroles-3-formic acid (II), in the thionyl chloride solvent, refluxing down, reaction generates intermediate III.Intermediate III and substituted aminated compounds are at methylene dichloride, trichloromethane, acetone, N; In dinethylformamide or the toluene equal solvent; Under the catalysis with acid binding agents such as triethylamine, pyridine, salt of wormwood, yellow soda ash, sodium hydrogencarbonate, saleratus, sodium hydroxide or Pottasium Hydroxide ,-10～50 ℃ of reacting generating compound I.
Reaction makes all cpds or products therefrom is dissolved in DMF, acetone, methyl alcohol, ethanol, DMSO or the ether dropping inorganic acid, organic acid processes pharmacy acceptable salt.
Specifically be that all cpds is dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ETHYLE ACETATE or the DMSO, the dripping hydrochloric acid ether is processed hydrochloride to pH=2 under ice-water bath; Or all cpds is dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ETHYLE ACETATE or the DMSO, and adding and wait a mole taurine, heated and stirred gets its taurate; Or all cpds is dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ETHYLE ACETATE or the DMSO, drips the vitriol oil down to pH=3, process vitriol in ice-water bath, or the like.
This compounds is effective for the treatment human malignancies.Although compound of the present invention can be without the direct administration of any preparation, described all cpds preferably uses with the form of pharmaceutical prepn, and route of administration can be non-enteron aisle approach (like vein, muscle administration) and oral administration.
The preparation of pharmaceutical compositions of The compounds of this invention is following: use standard and conventional technology; Acceptable solid or liquid vehicle are combined, and make it at random with technology of pharmaceutics on acceptable auxiliary and vehicle combine to be prepared into particulate or microballoon.Solid dosage comprises tablet, discrete particles, capsule, slow releasing tablet, sustained release pellet or the like.Solid carrier can be at least a material, and it can serve as thinner, flavouring agent, solubilizing agent, lubricant, suspension agent, tackiness agent, disintegrating agent and coating agent.Inert solid carrier comprises trimagnesium phosphate, Magnesium Stearate, smoothers sugar, lactose, pectin, Ucar 35, Polysorbate 80, dextrin, starch, gelatin, cellulose substances for example methylcellulose gum, Microcrystalline Cellulose, low melt point paraffin, polyoxyethylene glycol, N.F,USP MANNITOL, theobroma oil etc.Liquid dosage form comprises solvent, suspension-s for example injection, pulvis or the like.
The amount of the active ingredient that contains in pharmaceutical composition and the unit dosage form (The compounds of this invention) can specifically be applied according to patient's the state of an illness, the situation of diagnosis; The amount of used compound or concentration are regulated in the scope of a broad; Usually, the weight range of active compound is 0.5%～90% (weight) of compsn.Another preferred range is 0.5%～70%.
Compound or its pharmacy acceptable salt with formula I structure of the present invention has the obvious suppression effect external to tumour.
External antitumor action
(1) experimental technique:
Adopt classical cytotoxic activity vitro detection method mtt assay, detect the cell proliferation toxicity of invention compound the human tumor cells of vitro culture.
(2) experiment material:
Laboratory sample: formula I compound is provided by contriver's self-control.Sample is with the DMSO hydrotropy during experiment, and serum-free DMEM substratum is diluted to desired concn, and sample segment solution is suspension.
Main agents: MTT, the packing of Amresco company, lot number: 04M0904; Complete DMEM substratum, Gibco Company products, lot number: 1290007; Calf serum, Lanzhou people's marine life, lot number: 20060509; Trypsinase, the packing of Amresco company, lot number: 016B0604; Fluorouracil Injection, 0.25g/10ml (propping up), lot number: 0512022, Tianjin gold credit amino acid ltd.
Laboratory apparatus: Bechtop, Suzhou Decontamination Equipment Plant; CO
2Incubator, Thermo company, model: HERA Cell150; Inverted microscope, Carl Zeiss company, model: Axiovert 200; Enzyme-linked immunosorbent assay instrument, TECAN company, model: Sunrise; Whizzer, Kerdro company, model: Heraeus.
Cell strain: SPCA1 human lung adenocarcinoma cell line, MCF7 human breast cancer cell, SGC-7901 gastric carcinoma cells, all available from Shanghai cell research institute of the Chinese Academy of Sciences.
(3) experimental procedure:
Cell cultures: tumor cell inoculation is containing 10% calf serum, in the DMEM nutrient solution of 100IU/ml penicillin G sodium salt and 100 μ g/ml Vetstreps, places 37 ℃, 100% relative humidity, contains 5%CO
2Incubator in, it is subsequent use after 3 times to go down to posterity.
Mtt assay is measured: the cell in the vegetative period of taking the logarithm; Behind 0.25% tryptic digestion (suspension cell need not digest); Be suspended in the DMEM nutrient solution that contains 10% calf serum, blow and beat into single cell suspension gently with the glass dropper, microscopically is with blood cell counts plate numeration viable cell.(cell concn is adjusted into 6～10 * 10 to the every hole of 96 well culture plates inoculating cell suspension 90 μ L
4Individual/ml), at 37 ℃, 100% relative humidity, contain 5%CO
2, 95% air incubator cultivate 24h after, every hole adds 10 μ L soups (final concentration is made as: 40 μ g/ml, 20 μ g/ml, 10 μ g/ml, 5 μ g/ml and five concentration of 2.5 μ g/ml).In addition, each concentration is established negative control (isoconcentration DMSO) and blank background (not adding cell), and each group is all established 6 multiple holes.Cultured continuously 24h again, every then hole adds the MTT solution 10 μ l of 5mg/ml, and after continuing to cultivate 4h, the careful suction removed supernatant (suspension cell needs earlier centrifugally, inhales and removes supernatant).Every hole adds 100 μ lDMSO, puts micro oscillator concussion 5min so that crystallization is dissolved fully, and the single wavelength colorimetric of ELIASA 492nm is measured the OD value.Calculate inhibitory rate of cell growth as evaluation index with following method.
Inhibiting rate (%)=[1-(experimental group OD average-blank control group OD average)/(control group OD average-blank control group OD average)] * 100%.According to inhibitory rate of cell growth, calculate IC with the straight-line regression method
50Value.
(4) experimental result:
IC to the tumour cell of vitro culture
50(μ g/ml)
(5) conclusion:
According to above-mentioned in vitro tests result, we can find out that the compound with formula I structure has more intense restraining effect to above-mentioned 3 kinds of human tumor cells.
Description of drawings
Fig. 1 is the structural formula figure of formula I compound.
Embodiment
Below in conjunction with embodiment the present invention is done further explanation, it is indicative that embodiment is merely, and means that never it limits scope of the present invention by any way.Described compound is through performance liquid chromatography (HPLC), and thin-layer chromatography (TLC) detects.Can adopt subsequently such as ir spectra (IR), nuclear magnetic resonance spectrum (
1H NMR,
13C NMR), mass spectrum (MS) etc. is further proved conclusively its structure.
Embodiment 1: intermediate III-1
In the reaction flask that stirring, condensing surface, TM are housed, add 22.1g (0.1mol) 4-ethanoyl-1-Trimetylene-2,5-dimethyl--1H-pyrroles-3-carboxylic acid dissolves it with the 200ml thionyl chloride, stirs back flow reaction 4h (the flaggy demonstration reacts completely).With the thionyl chloride evaporate to dryness, promptly get white solid (HPLC:99.7%).HRMS(m/z)[M+H]
+：241.0684。
Embodiment 2:4-ethanoyl-N, N-two (2-chloroethyl)-1-cyclopropyl-2,5-dimethyl--1H-pyrroles-3-acid amides (compound I-1)
, the reaction flask that stirring, temperature take into account condensing surface adds 23.9g (0.1mol) intermediate III-1,21.4g (0.12mol) two (2-chloroethyl) ammonia hydrochloric acid salt, 20.2g triethylamine and 200ml DMF in being housed; Stir, back flow reaction 5h, the TLC demonstration reacts completely; Saturated common salt water washing (50ml * 3), dichloromethane layer is used anhydrous sodium sulfate drying, filters; Remove solvent under reduced pressure; Promptly get faint yellow solid, post separates [moving phase: v (sherwood oil): v (ETHYLE ACETATE)=1: 1], can get white solid (HPLC:99.5%).HRMS(m/z)[M+H]
+：293.1279。
With reference to the method for embodiment 1, can synthetic compound I-2～I-5.
Embodiment 3:4-ethanoyl-1-cyclopropyl-N, N-two (2-itrate group ethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide (compound I-6)
In the reaction flask that stirring, condensing surface, TM are housed, add compound I-1 (2.9g; 0.01mol), anhydrous acetonitrile (30ml) dissolving adds Silver Nitrate (2.0g; 0.012mol) anhydrous acetonitrile (10ml); Lucifuge stirs refluxed 5h, and the TLC demonstration reacts completely postcooling to room temperature, the evaporated under reduced pressure solvent.Add methylene dichloride (20ml) in the residuum, stir 10min, filter the filtrate decompression solvent evaporated.Add absolute ethyl alcohol (30ml), evaporated under reduced pressure behind activated carbon decolorizing, reduced pressure at room temperature is spent the night, and obtains yellow transparent oily matter I-6 (3.6g, yield 90%), purity 99.2% (HPLC method).HRMS(m/z)[M+H]
+：339.1471。
Embodiment 4:4-ethanoyl-1-cyclopropyl-N-(2-itrate group ethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide (compound I-7)
In the reaction flask that stirring, condensing surface, TM are housed, 6.5ml nitrosonitric acid, 19.5ml aceticanhydride are mixed; Controlled temperature is at-15 ℃, to wherein dripping compound I-5 (2.7g, tetrahydrofuran solution 100ml 0.01mol); Drip and finish; Slowly rise to room temperature, reaction 4h drips the frozen water stopped reaction.Reaction mixture is used the 200ml acetic acid ethyl dissolution, washes with 200ml water, 200ml saturated sodium bicarbonate solution successively, washes with 200ml water, 200ml saturated nacl aqueous solution again.Organic layer is used anhydrous magnesium sulfate drying.Concentrating under reduced pressure, crude product get faint yellow oily thing 1.9g, yield 62%, purity 99.2% through column chromatography [v (sherwood oil): v (ETHYLE ACETATE)=1: 1] purifying.HRMS(m/z)[M+H]
+：310.1358。
Embodiment 5:
Compound I-1 one-tenth hydrochloride: get compound I-1 white solid product 2.0g, be dissolved in the 10ml absolute ethyl alcohol.Ice-water bath is cooled to 5 ℃, drip 11.1% ethanol solution hydrochloride to pH be 2, continue at stir about 1h under the ice-water bath.Filter, vacuum-drying gets the white solid powder.
Embodiment 6:
Compound I-6 one-tenth taurate: get compound I-6 yellow oil 2.0g, be dissolved in the 10ml anhydrous methanol.Be heated to the back adding that refluxes and wait a mole taurine, continue at the about 1.5h of stirring reaction down that refluxes.Reaction finishes, and under room temperature, leaves standstill 24h.Separate out light yellow crystallization, filter vacuum-drying.
Embodiment 7:
Compound I-7 one-tenth vitriol: get the faint yellow oily thing of compound I-7 2.0g, be dissolved in 15ml acetone.Ice-water bath is cooled to 0 ℃, drip concentrated sulfuric acid solution to pH be 3, continue at stir about 1h under the ice-water bath.Filter, get white solid.
Pharmaceutical composition for amide compound that the pyrroles of containing of the present invention is described more fully provides following FORMULATION EXAMPLE below, and said embodiment only is used for explanation, rather than is used to limit scope of the present invention.Said preparation can use any active compound and the salt thereof in the The compounds of this invention, preferably uses the compound described in the embodiment 1-6.
Embodiment 8:
Prepare hard gelatin capsule with following compositions:
Preparation technology: supplementary material is dry in advance, and it is subsequent use to cross 100 mesh sieves.After pressing recipe quantity mentioned component being mixed, be packed in the hard gelatin capsule.
Embodiment 9:
Prepare tablet with following compositions:
Preparation technology: supplementary material is dry in advance, and it is subsequent use to cross 100 mesh sieves.Earlier with the abundant mixing of the auxiliary material of recipe quantity.Bulk drug is added in the auxiliary material to increase progressively dilution method, and each abundant mixing of added-time 2～3 times guarantees medicine and the abundant mixing of auxiliary material; Cross 20 mesh sieves, dry 2h in 55 ℃ of ventilated drying ovens, dried particle cross the whole grain of 16 mesh sieves; Measure midbody content, mix compressing tablet on tabletting machine.
Embodiment 10:
The preparation of injection liquid:
Preparing method: get activeconstituents and join in the water for injection that dissolves polysorbate and Ucar 35, add medicinal basic adjusting pH value to 4～8 and make its dissolving.Add gac, whip attachment 30min, carbon removal, smart filter, embedding, sterilization.
Embodiment 11:
The preparation of injection lyophilized powder:
The taurate 100mg of compound I-2
Medicinal basic 0.1～7.0%
N.F,USP MANNITOL 55～85%
Preparing method: get activeconstituents and add water for injection, regulate pH value to 4～8 with medicinal basic and make its dissolving.Add N.F,USP MANNITOL again, carry out autoclaving by the requirement of injection, add gac, adopt filtering with microporous membrane, filtrating is carried out packing, adopts freeze-drying, makes loose block, seals, and promptly gets.
Claims (8)
1. the compound or its pharmacy acceptable salt that have formula I structure:
Wherein:
R
1, R
2, R
3, R
4For: C
1-C
6The straight or branched alkyl, C
3-C
6Naphthenic base;
R
5, R
6Be at the same time or separately: hydrogen, C
1-C
6Alkyl; Hydroxyl, halogen, C
1-C
4Alkoxyl group, the substituted C of itrate group
1-C
6Alkyl.
2. compound as claimed in claim 1 or its pharmacy acceptable salt, said compound is:
I-1.4-ethanoyl-N, N-two (2-chloroethyl)-1-cyclopropyl-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-2.4-ethanoyl-1-cyclopropyl-N, N-two (2-hydroxyethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-3.4-ethanoyl-1-cyclopropyl-N, N-two (2-methoxyethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-4.4-ethanoyl-N-(2-chloroethyl)-1-cyclopropyl-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-5.4-ethanoyl-1-cyclopropyl-N-(2-hydroxyethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-6.4-ethanoyl-1-cyclopropyl-N, N-two (2-itrate group ethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide
I-7.4-ethanoyl-1-cyclopropyl-N-(2-itrate group ethyl)-2,5-dimethyl--1H-pyrrole-3-carboxamide
3. formula I compound as claimed in claim 1 or its pharmacy acceptable salt, its pharmacy acceptable salt is: formula I compound and mineral acid, organic acid salify.
4. formula I compound as claimed in claim 3 or its pharmacy acceptable salt; Its pharmacy acceptable salt is: hydrochloride, hydrobromate, hydriodate, vitriol, hydrosulfate, phosphoric acid salt, acetate, propionic salt, butyrates, lactic acid salt, mesylate; Tosilate, PHENRAMINE MALEATE, benzoate, SUMATRIPTAN SUCCINATE, tartrate, Citrate trianion, fumarate, taurate.
5. the preparation method of the described formula I compound of claim 1; It is characterized in that: substituted 1H-pyrroles-3-formic acid (II); Generate intermediate III with thionyl chloride reaction, intermediate III and substituted aminated compounds under the catalysis of acid binding agent ,-10～50 ℃ of reacting generating compound I.
R
1, R
2, R
3, R
4, R
5, R
6Definition according to claim 1.
6. antitumor medicine composition, it comprises each compound or its pharmacy acceptable salt and one or more pharmaceutical carriers of claim 1-2 of treating significant quantity.
7. each compound or its pharmacy acceptable salt application aspect the preparation antitumor drug of claim 1-2.
8. application as claimed in claim 7 is used to prepare the purposes of the medicine aspect of treatment mammary cancer, lung cancer, cancer of the stomach.
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Cited By (2)
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|---|---|---|---|---|
| WO2016107544A1 (en) * | 2014-12-29 | 2016-07-07 | 成都先导药物开发有限公司 | Intermediate compound for preparing pyrrole amide compound and preparation method and use thereof |
| US10266489B2 (en) | 2014-12-29 | 2019-04-23 | Hitgen Ltd | Pyrrolic amide compound and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1280566A (en) * | 1997-11-13 | 2001-01-17 | 辉瑞产品公司 | The synthetic method of pyrrolamide |
| CN1484637A (en) * | 2000-11-08 | 2004-03-24 | �ӳɹ� | Pyrrole carboxamide and pyrrole thiocarboxamide and their application in pesticides |
| CN1491212A (en) * | 2001-02-09 | 2004-04-21 | �ӳɹ� | Application of pyrrole carboxamide as fungicide |
-
2012
- 2012-06-04 CN CN201210179789.2A patent/CN102786458B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1280566A (en) * | 1997-11-13 | 2001-01-17 | 辉瑞产品公司 | The synthetic method of pyrrolamide |
| CN1484637A (en) * | 2000-11-08 | 2004-03-24 | �ӳɹ� | Pyrrole carboxamide and pyrrole thiocarboxamide and their application in pesticides |
| CN1491212A (en) * | 2001-02-09 | 2004-04-21 | �ӳɹ� | Application of pyrrole carboxamide as fungicide |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016107544A1 (en) * | 2014-12-29 | 2016-07-07 | 成都先导药物开发有限公司 | Intermediate compound for preparing pyrrole amide compound and preparation method and use thereof |
| US10266489B2 (en) | 2014-12-29 | 2019-04-23 | Hitgen Ltd | Pyrrolic amide compound and preparation method and application thereof |
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