CN105622558A - Acylhydrazone derivative containing benzofuran ring and preparation method and application of acylhydrazone derivative - Google Patents
Acylhydrazone derivative containing benzofuran ring and preparation method and application of acylhydrazone derivative Download PDFInfo
- Publication number
- CN105622558A CN105622558A CN201610100379.2A CN201610100379A CN105622558A CN 105622558 A CN105622558 A CN 105622558A CN 201610100379 A CN201610100379 A CN 201610100379A CN 105622558 A CN105622558 A CN 105622558A
- Authority
- CN
- China
- Prior art keywords
- benzofuran ring
- preparation
- alkyl
- acylhydrazone derivative
- pharmaceutically acceptable
- 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
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an acylhydrazone derivative which is as indicated in the structural formula (I) and contains a benzofuran ring, pharmaceutically acceptable salt of the acylhydrazone derivative, a preparation method and medicine composition of the acylhydrazone derivative and application of the acylhydrazone derivative to preparation of influenza virus neuraminidase inhibitor.The structural formula can be found in the specification, wherein R is selected from hydrogen, deuterium, C1-C2 alkyl and C3-C5 straight chain alkyl or C3-C5 branched chain alkyl; R1 is selected from C1-C2 alkyl and C3-C17 straight chain alkyl or C3-C17 branched chain alkyl.
Description
Technical field
The present invention relates to class noval chemical compound and preparation method thereof and application; The specifically preparation containing the acyl hydrazone derivative of benzofuran ring and the application as influenza virus neuraminidase inhibitor.
Background technology
The anti-influenza virus medicament listed as neuraminidase inhibitor mainly has zanamivir (Zanamivir), GS-4104 (Oseltamivir) and Peramivir (Peramivir).
Duarte etc. [Bioorg.Med.Chem., 2007,15:2421-2433] have synthesized the acylhydrazone containing piperonyl cyclonene, it has been found that it has good anti-inflammatory activity.
Acylhydrazone structure is introduced in indole ring by Ye Ying etc. [organic chemistry, 2009,29 (6): 993-997], and antibacterial activity test shows, the indole acylhydrazone MIC to staphylococcus aureus50Value and MBC value respectively 0.612 �� g/mL and 1.10 �� g/mL, lower than the antibacterials profit azoles amine (1��8 �� g/mL) used by clinic, Linezolid (1��4 �� g/mL) and amikacin (1.56 �� g/mL).
Basu etc. [JournalofVirology, 2009,83 (4): 1881-1891] report the anti-influenza virus activity of compound N SC125044. Duarte etc. [Bioorg.Med.Chem., 2012,20:487-497] have synthesized a series of 2-(2-hydroxybenzoyl) hydrazone compound on this basis, it has been found that they all have certain anti-influenza virus activity.
Barman etc. [Eur.J.Med.Chem., 2014,71:81-90] have synthesized a series of naphthalene-ring containing acyl hydrazone derivative, and test its inhibitory activity to influenza A virus, it has been found that when having hydroxyl to replace for 2 of naphthalene nucleus, and activity is better. Shih etc. [J.Biomed.Sci, 2010,17:13] describe the BPR1P0034 inhibitory activity for various subtype influenza virus, it has been found that suitable for its inhibitory activity of part hypotype and positive control zanamivir.
Chinese invention patent [CN103360315] has synthesized the assorted oxygen acetyl hydrazone of a series of virtue containing pyrazoles, and tests its inhibitory activity to H1N1 influenza virus, the EC of outstanding compound50Less than 10 ��Ms. Fedichev etc. [PLOSCurrentsInfluenza.2011] describe the inhibitory action for multiple subtype influenza virus of the acyl hydrazone derivative containing 1,2,4-triazole.
Summary of the invention
Present invention solves the technical problem that and be to provide a class containing the acyl hydrazone derivative of benzofuran ring, its preparation method, pharmaceutical composition and purposes.
For solving the technical problem of the present invention, the present invention provides following technical scheme:
The first aspect of technical solution of the present invention there is provided a class such as acyl hydrazone derivative containing benzofuran ring shown in chemical constitution formula I and pharmaceutically acceptable salt thereof:
Wherein R is selected from: hydrogen, deuterium, C1��C2Alkyl, C3��C5Straight chained alkyl or C3��C5Branched alkyl; R1It is selected from: C1��C2Alkyl, C3��C17Straight chained alkyl or C3��C17Branched alkyl; The acyl hydrazone derivative chemistry containing benzofuran ring shown in formula I is called 1-[4-hydroxyl/alkoxyl-3-(2-methyl benzofuran-5-base) phenyl]-2-acetone fat acylhydrazone.
The preparation method that the second aspect of technical solution of the present invention there is provided the acyl hydrazone derivative described in first aspect containing benzofuran ring, it is characterised in that its preparation reaction is as follows:
Wherein R is selected from: hydrogen, deuterium, C1��C2Alkyl, C3��C5Straight chained alkyl or C3��C5Branched alkyl; R1It is selected from: C1��C2Alkyl, C3��C17Straight chained alkyl or C3��C17Branched alkyl.
The third aspect of technical solution of the present invention is to provide the pharmaceutical composition containing compound described in first aspect and pharmaceutically acceptable salt thereof, this pharmaceutical composition contains the acyl hydrazone derivative containing benzofuran ring and the pharmaceutically acceptable salt thereof of the present invention of therapeutically effective amount, and optional containing pharmaceutical carrier. Wherein said pharmaceutical carrier refers to the pharmaceutical carrier that pharmaceutical field is conventional; This pharmaceutical composition can be prepared according to method well known in the art. Can pass through, by the compounds of this invention and pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable solids or liquid excipient and/or adjuvant combination, to make any dosage form being suitable to human or animal's use. The compounds of this invention and pharmaceutically acceptable salt content in its pharmaceutical composition thereof are generally 0.1%��95% percentage by weight.
The compounds of this invention and pharmaceutically acceptable salt or the pharmaceutical composition containing it thereof can be administered in a unit, route of administration can be intestinal or non-bowel, such as oral, intravenous injection, intramuscular injection, subcutaneous injection, nasal cavity, oral mucosa, eye, lung and respiratory tract, skin, vagina, rectum etc.
Form of administration can be liquid dosage form, solid dosage forms or semisolid dosage form. Liquid dosage form can be solution (including true solution and colloid solution), Emulsion (including o/w type, w/o type and emulsion), suspensoid, injection (including aqueous injection, injectable powder and transfusion), eye drop, nasal drop, lotion and liniment etc.; Solid dosage forms can be tablet (including ordinary tablet, enteric coatel tablets, buccal tablet, dispersible tablet, chewable tablet, effervescent tablet, oral cavity disintegration tablet), capsule (including hard capsule, soft capsule, enteric coated capsule), granule, powder, micropill, drop pill, suppository, membrane, paster, gas (powder) mist agent, spray etc.; Semisolid dosage form can be ointment, gel, paste etc.
The compounds of this invention and pharmaceutically acceptable salt thereof can be made ordinary preparation, also make is slow releasing preparation, controlled release preparation, targeting preparation and various particulate delivery system.
In order to the compounds of this invention and pharmaceutically acceptable salt thereof are made tablet, it is possible to widely use various excipient well known in the art, including diluent, adhesive, wetting agent, disintegrating agent, lubricant, fluidizer. Diluent can be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline Cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate etc.; Wetting agent can be water, ethanol, isopropanol etc.; Binding agent can be starch slurry, dextrin, syrup, Mel, glucose solution, microcrystalline Cellulose, mucialga of arabic gummy, gelatine size, sodium carboxymethyl cellulose, methylcellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, Polyethylene Glycol etc.; Disintegrating agent can be dried starch, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, sodium bicarbonate and citric acid, polyoxyethylene sorbitol fatty acid ester, dodecyl sodium sulfate etc.; Lubricant and fluidizer can be Pulvis Talci, silicon dioxide, stearate, tartaric acid, liquid paraffin, Polyethylene Glycol etc.
Tablet can also be made coated tablet further, for instance sugar coated tablet, thin membrane coated tablet, ECT, or double-layer tablet and multilayer tablet.
In order to administration unit is made capsule, it is possible to effective ingredient the compounds of this invention and pharmaceutically acceptable salt thereof are mixed with diluent, fluidizer, mixture is placed directly within hard capsule or soft capsule. Also effective ingredient the compounds of this invention and pharmaceutically acceptable salt thereof first can be made granule or micropill with diluent, adhesive, disintegrating agent, then be placed in hard capsule or soft capsule. For preparing each diluent of the compounds of this invention and pharmaceutically acceptable salt tablet thereof, adhesive, wetting agent, disintegrating agent, fluidizer kind can also be used for preparing the capsule of the compounds of this invention and pharmaceutically acceptable salt thereof.
For the compounds of this invention and pharmaceutically acceptable salt thereof are made injection, it is possible to adjust agent, osmotic pressure regulator with water, ethanol, isopropanol, propylene glycol or their mixture as solvent addition solubilizing agent commonly used in the art in right amount, cosolvent, pH. Solubilizing agent or cosolvent can be poloxamer, lecithin, HP-��-CD etc.; PH adjustment agent can be phosphate, acetate, hydrochloric acid, sodium hydroxide etc.; Osmotic pressure regulator can be sodium chloride, mannitol, glucose, phosphate, acetate etc. As prepared lyophilized injectable powder, mannitol, glucose etc. also can be added as proppant.
Additionally, if desired, coloring agent, preservative, spice, correctives or other additive can also be added in pharmaceutical preparation.
For reaching medication purpose, strengthening therapeutic effect, the medicine of the present invention or pharmaceutical composition can be administered by any known medication.
The fourth aspect of technical solution of the present invention is to provide described in first aspect present invention containing pharmaceutical composition application in preparing influenza virus neuraminidase inhibitor described in the acyl hydrazone derivative of benzofuran ring and pharmaceutically acceptable salt and the third aspect thereof.
Advantageous Effects:
The acyl hydrazone derivative containing benzofuran ring of the present invention is the compound with influenza neuraminidase inhibitory activity of a class new construction type.
Detailed description of the invention
Following example are intended to illustrate the present invention rather than limitation of the invention further.
Embodiment 1
The preparation of 1-[4-hydroxyl-3-(2-methyl benzofuran-5-base) phenyl]-2-acetone
(1) preparation of 4-pi-allyl-2-(2-methyl benzofuran-5-base) phenol
Autoclave adds 10mmol honokiol, 0.2mmolPdCl2, 2.0mmolNaOAc, 56mlDMA/H2O (6:1), logical 8atmO2, react 16h in 60 DEG C. After reaction terminates, add the dilution of 100ml water, by 3 �� 30ml extraction into ethyl acetate, anhydrous Na2SO4Dry, vacuum distillation recovered solvent. Crude product purifies through column chromatography, obtains yellow oily liquid 4-pi-allyl-2-(2-methyl benzofuran-5-base) phenol, yield 86.0%.1HNMR(400MHz,CDCl3) ��: 7.53 (d, J=1.5Hz, 1H, benzofuran ring 4-H), 7.50 (d, J=8.4Hz, 1H, benzofuran ring 7-H), 7.26 (dd, J=8.4,1.5Hz, 1H, benzofuran ring 6-H), 7.10��7.07 (m, 2H, C6H33,5-H), 6.94 (d, J=8.8Hz, 1H, C6H36-H), 6.41 (s, 1H, benzofuran ring 3-H), 5.98 (ddt, J=16.9,10.0,6.7Hz, 1H ,=CH), 5.21 (s, 1H, OH), 5.13��5.03 (m, 2H ,=CH2), 3.36 (d, J=6.7Hz, 2H, CH2), 2.49 (s, 3H, CH3)��
(2) preparation of 1-[4-hydroxyl-3-(2-methyl benzofuran-5-base) phenyl]-2-acetone
Autoclave adds 10mmol4-pi-allyl-2-(2-methyl benzofuran-5-base) phenol, 0.15mmolPdCl2, 40mlDMA/H2O (4:1), logical 8atmO2, react 10h in 60 DEG C. After reaction terminates, add the dilution of 100ml water, by 3 �� 30ml extraction into ethyl acetate, anhydrous Na2SO4Dry, vacuum distillation recovered solvent. Crude product purifies through column chromatography, obtains white solid 1-[4-hydroxyl-3-(2-methyl benzofuran-5-base) phenyl]-2-acetone, yield 63.9%; Fusing point 118��121 DEG C;1HNMR (400MHz, CDCl3) ��: 7.52 (d, J=1.6Hz, 1H, benzofuran ring 4-H), 7.49 (d, J=8.4Hz, 1H, benzofuran ring 7-H), 7.25 (dd, J=8.4,1.8Hz, 1H, benzofuran ring 6-H), 7.10��7.07 (m, 2H, C6H33,5-H), 6.97 (d, J=7.8Hz, 1H, C6H36-H), 6.41 (s, 1H, benzofuran ring 3-H), 5.35 (br, 1H, OH), 3.66 (s, 2H, CH2), 2.49 (s, 3H, benzofuran ring 2-CH3), 2.18 (s, 3H, CH3)��
Embodiment 2
The preparation of 1-[4-hydroxyl-3-(2-methyl benzofuran-5-base) phenyl]-2-acetone acetyl hydrazone
0.5mmol1-[4-hydroxyl-3-(2-methyl benzofuran-5-base) phenyl]-2-acetone, 1.0mmol acethydrazide, add 0.2ml glacial acetic acid with 20ml ethanol after dissolving, after reacting 5h in 50 DEG C, adding 50ml ethanol, decompression is distilled to residue 5ml solution, and TLC monitoring reaction is complete. Adding a large amount of water, fully shake, stand, precipitate out solid, filter, filter cake washes with water, dries to obtain faint yellow solid 1-[4-hydroxyl-3-(2-methyl benzofuran-5-base) phenyl]-2-acetone acetyl hydrazone, yield 58.9%; Fusing point 92��95 DEG C.1HNMR(400MHz,CDCl3) ��: 7.57-7.53 (m, 2H, benzofuran ring 4,7-H), 7.28��7.24 (m, 1H, benzofuran ring 6-H), 7.10��7.08 (m, 1H, C6H33-H), 7.06��7.02 (m, 1H, C6H35-H), 6.98��6.94 (m, 1H, C6H36-H), 6.43 (s, 1H, benzofuran ring 3-H), 5.70 (br, 1H, OH), 5.38 (br, 1H, NH), 3.66 (s, 1H, CH2), 3.52 (s, 2H, CH2), 2.50 (s, 3H, COCH3), 2.49 (s, 3H, benzofuran ring 2-CH3), 2.35 (s, 3H, CH3)��
Embodiment 3
The resisiting influenza virus neuraminidase activity of the acyl hydrazone derivative containing benzofuran ring
1. experimental principle
Compound MUNANA is the specific substrate of neuraminidase, and the metabolite produced under neuraminidase effect is under 360nm irradiates and excites, it is possible to producing 450nm fluorescence, the change of fluorescence intensity can react neuraminidase activity delicately. Enzyme both is from A/PR/8/34 (H1N1) virus stain.
2. experimental technique
In enzyme reaction system, finite concentration sample and influenza virus god NA are suspended in reaction buffer (pH6.5), add fluorogenic substrate MUNANA and start reaction system, 37 DEG C hatch 40 minutes after, add reaction terminating liquid and terminate reaction. Under the Parameter Conditions that excitation wavelength 360nm and transmitting wavelength are 450nm, measure fluorescence intensity level. The fluorescence intensity of reaction system can reflect the activity of enzyme. Minimizing amount according to fluorescence intensity can the computerized compound suppression ratio to NA activity.
3. detection sample: embodiment compound.
4. Activity Results
Preferred 1-[4-hydroxyl-3-(2-methyl benzofuran-5-base) phenyl]-2-acetone acetyl hydrazone honokiol in response system during detectable concentration 40.0 �� g/mL to the suppression ratio of neuraminidase respectively 40.87% and 4.37%.
Neuraminidase is had good inhibitory activity by the acyl hydrazone derivative containing benzofuran ring, and inhibitory activity is better than honokiol, can be applicable to prepare neuraminidase inhibitor.
Claims (4)
1. shown in a class chemical constitution formula I the acyl hydrazone derivative containing benzofuran ring and pharmaceutically acceptable salt:
Wherein R is selected from: hydrogen, deuterium, C1��C2Alkyl, C3��C5Straight chained alkyl or C3��C5Branched alkyl; R1It is selected from: C1��C2Alkyl, C3��C17Straight chained alkyl or C3��C17Branched alkyl.
2. the preparation method of the acyl hydrazone derivative containing benzofuran ring described in claim 1, it is characterised in that its preparation reaction is as follows:
In formula, R, R1Definition as claimed in claim 1.
3. the application in preparing influenza virus neuraminidase inhibitor of the acyl hydrazone derivative containing benzofuran ring described in claim 1.
4. a pharmaceutical composition, including carrier available at least one compound of claim 1 and pharmacopedics.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610100379.2A CN105622558B (en) | 2016-02-24 | 2016-02-24 | Acyl hydrazone derivative of the ring containing benzofuran and preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610100379.2A CN105622558B (en) | 2016-02-24 | 2016-02-24 | Acyl hydrazone derivative of the ring containing benzofuran and preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105622558A true CN105622558A (en) | 2016-06-01 |
| CN105622558B CN105622558B (en) | 2017-12-29 |
Family
ID=56037942
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610100379.2A Expired - Fee Related CN105622558B (en) | 2016-02-24 | 2016-02-24 | Acyl hydrazone derivative of the ring containing benzofuran and preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105622558B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108272786A (en) * | 2018-04-17 | 2018-07-13 | 南华大学 | The medical usage of 1- [3- (benzofuran -5- bases) phenyl] -2- acetone benzoyl hydrazones |
| CN109096231A (en) * | 2018-09-12 | 2018-12-28 | 长沙理工大学 | 4- allyl -2- (benzofuran -5- base) phenol and its application |
| CN110183349A (en) * | 2019-06-11 | 2019-08-30 | 湖南大学 | Oxalyl hydazone derivative and the preparation method and application thereof |
| CN110950825A (en) * | 2018-09-27 | 2020-04-03 | 湖南大学 | 6- (piperazinemethyl) -2- (benzofuran-5-yl) phenol and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101223120A (en) * | 2005-02-23 | 2008-07-16 | 杰克·L·阿比瑟 | Honokiol derivatives for the treatment of proliferative disorders |
| WO2013056003A2 (en) * | 2011-10-12 | 2013-04-18 | Yale University | Catechol diethers as potent anti-hiv agents |
| CN103127040A (en) * | 2011-11-29 | 2013-06-05 | 天津市国际生物医药联合研究院 | Application of cortex magnolia officinal extract in preparing medicine for healing and preventing acquired immune deficiency syndrome |
-
2016
- 2016-02-24 CN CN201610100379.2A patent/CN105622558B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101223120A (en) * | 2005-02-23 | 2008-07-16 | 杰克·L·阿比瑟 | Honokiol derivatives for the treatment of proliferative disorders |
| WO2013056003A2 (en) * | 2011-10-12 | 2013-04-18 | Yale University | Catechol diethers as potent anti-hiv agents |
| CN103127040A (en) * | 2011-11-29 | 2013-06-05 | 天津市国际生物医药联合研究院 | Application of cortex magnolia officinal extract in preparing medicine for healing and preventing acquired immune deficiency syndrome |
Non-Patent Citations (1)
| Title |
|---|
| 张建国 等: "神经氨酸酶抑制剂的研究进展", 《化学与生物工程》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108272786A (en) * | 2018-04-17 | 2018-07-13 | 南华大学 | The medical usage of 1- [3- (benzofuran -5- bases) phenyl] -2- acetone benzoyl hydrazones |
| CN108272786B (en) * | 2018-04-17 | 2022-05-27 | 南华大学 | Medical application of 1- [3- (benzofuran-5-yl) phenyl ] -2-acetone benzoyl hydrazone |
| CN109096231A (en) * | 2018-09-12 | 2018-12-28 | 长沙理工大学 | 4- allyl -2- (benzofuran -5- base) phenol and its application |
| CN110950825A (en) * | 2018-09-27 | 2020-04-03 | 湖南大学 | 6- (piperazinemethyl) -2- (benzofuran-5-yl) phenol and application thereof |
| CN110950825B (en) * | 2018-09-27 | 2023-01-03 | 湖南大学 | 6- (piperazinemethyl) -2- (benzofuran-5-yl) phenol and application thereof as anti-cancer drug |
| CN110183349A (en) * | 2019-06-11 | 2019-08-30 | 湖南大学 | Oxalyl hydazone derivative and the preparation method and application thereof |
| CN110183349B (en) * | 2019-06-11 | 2021-04-30 | 湖南大学 | Oxalyl hydrazone derivative and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105622558B (en) | 2017-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105622558A (en) | Acylhydrazone derivative containing benzofuran ring and preparation method and application of acylhydrazone derivative | |
| CN105693665A (en) | Aryl formyl hydrazone derivative including benzofuran ring and preparing method and medical application of aryl formyl hydrazone derivative | |
| CN105777664B (en) | Carboxylate of 2 (2 benzyl hydrazono-) thiazole 5 and preparation method thereof and medical usage | |
| CN108440468B (en) | 2- (benzofuran-5-yl) phenol and application thereof as anticancer drug | |
| CN107987033B (en) | Application of vanillin and isomer thereof in preparation of NA inhibitor | |
| CN105541859B (en) | Dihydrofuran and chromanone derivatives and preparation method thereof and medical usage | |
| CN108503604A (en) | (4- alkyl -5- acyl group -2- thiazoles) hydazone derivative and its medical usage | |
| CN111153898A (en) | Thiourea derivative and preparation method and application thereof | |
| CN110229081B (en) | 2, 4-dinitrophenylhydrazone derivative and preparation method and application thereof | |
| CN105541591B (en) | 1‑（The aryl phenyl of 4 hydroxyl 3）2 acetone and preparation method and application | |
| JP2009292789A (en) | Method for producing sialic acid derivative and its use as influenza virus inhibitor | |
| CN108047160A (en) | 2- (2- benzyls hydrazono-) -5- acyl groups thiazoles and its medical usage | |
| CN105669589A (en) | 2-(5-Acylthiazole-2-imino)-4-thiazolidinone and preparation method and application thereof | |
| CN102382076B (en) | Arone and aryl amide compound and preparation method thereof and medicinal usage | |
| CN115925640A (en) | ((3-carbamoyl-5-fluoropyrazin-2-yl) oxy) methyl isobutyrate and preparation method and application thereof | |
| KR102352728B1 (en) | Methods for reducing triglyceride, total cholesterol and low density lipoprotein blood levels | |
| CN107141267B (en) | N- (5- acyl group thiazol-2-yl) amide and the preparation method and application thereof | |
| CN109053606B (en) | 4- (4-hydroxyphenylmethyleneamino) -1,2, 4-triazole-5-thione and application thereof | |
| CN108689961B (en) | 2- (5-nitrothiazol-2-yl) imino-4-thiazolinone derivative and preparation method and application thereof | |
| CN110183349B (en) | Oxalyl hydrazone derivative and preparation method and application thereof | |
| CN111100074B (en) | Pyridazine hydrazone derivative and preparation method and application thereof | |
| CN107286149A (en) | N‑（The base of 5 piperonyl thiazole 2）Piperidyl amide and its application | |
| TW201302736A (en) | Cathepsin C inhibitors | |
| CN107118176B (en) | N-(5- benzyl thiazol-2-yl) morpholinyl amide and its medical usage | |
| CN111138377B (en) | Vanilamide derivative and 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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20171229 |