CN108341807A - Piperazine acidamide compound of the skeleton containing benzodioxan and its preparation method and application - Google Patents
Piperazine acidamide compound of the skeleton containing benzodioxan and its preparation method and application Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention belongs to non-steroidal anti-inflammatory drugs technical fields, and in particular to a kind of piperazine acidamide compound of the skeleton containing benzodioxan and its preparation method and application.The piperazine acidamide compound of the skeleton containing benzodioxan is prepared as mixing Isosorbide-5-Nitrae benzodioxan formylhydrazine with potassium hydroxide, methanol, and carbon disulfide, then back flow reaction are added dropwise under ice-water bath, is spin-dried for solvent, water is added to filter, acidification of filtrate obtains product a；By the substituent of piperazine, triethylamine and dichloromethane mix, and chloracetyl chloride is added dropwise under ice-water bath, react, and filtering obtains product b；Again by product a, product b, potassium hydroxide and methanol mixing, it is obtained by the reaction.The piperazine acidamide compound synthesis of present invention skeleton containing benzodioxan is simple, and convenient for purification, yield is higher, and property stable in the air is good；Preparation method is simple and practicable, is suitble to industrialized production.In addition, the present invention has preferable anti-inflammatory activity, it can be used for the preparation of non-steroidal anti-inflammatory drugs.
Description
Technical field
The invention belongs to non-steroidal anti-inflammatory drugs technical fields, and in particular to a kind of piperazine amide of the skeleton containing benzodioxan
Class compound and its preparation method and application.
Background technology
Inflammation is a kind of host defence mechanism of the body to infection, is mainly shown as redness, oedema, pain and fever etc..
Non-steroid anti-inflammatory drug (NSAIDs) such as Indomethacin, brufen, naproxen and fenbufen are that clinic is most commonly used to treatment inflammation
First-line drug.According to incompletely statistics, the whole world has people more than 100,000,000 using such drug.As the fiest-tire medication of anti-inflammatory and antalgic,
The adverse reaction of NSAIDs and side-effect problem are also more prominent.Therefore research and development have efficient and Small side effects non-steroidal anti-inflammatories
Drug has great importance.
Benzodioxan skeleton has very extensive bioactivity, the MOLECULE DESIGN and synthesis technology of such compound are ground
Study carefully hot spot always of people's attention.Such as Sun, J.；Wang,S.；Sheng,G.H.；Lian,Z.M.；Liu,H.Y.；Zhu,
H.L.Bioorg.Med.Chem.2016,24,5626-5632；Quaglia,W.；Piergentili,A.；Del Bello,F.；
Farande,Y.；Giannella,M.；Pigini,M.；Rafaiani,G.；Carrieri,A.；Amantini,C.；
Lucciarini,R.；Santoni,G.；Poggesi,E.；Leonardi,A.J.Med.Chem.2008,51,6359-6370；
Harrak,Y.；Rosell,G.；Daidone,G.；Plescia,S.；Schillaci,D.；Pujol,
M.D.Bioorg.Med.Chem.2007,15,4876-4890.Above documents disclose the compounds of the skeleton containing benzodioxan
Application in nonsteroidal anti-inflammatory drug field.
Piperazine ring is a kind of basic group, easily forms multiple ionic bonds or hydrogen bond with other molecules, can also be adjusted well
The acid-base balance constant and lipid of drug.It is introduced into drug molecule, can effectively increase the water solubility of drug
And alkalinity, improve the pharmacokinetic property of molecule.Bridged piperazine derivatives are because with anticancer, antibacterial, antidepression, anti-hypertension, disappearing
Inflammation analgesic etc. multiple biological activities and get more and more people's extensive concerning.Such as Khaled, R.R.；Abdellatifa,A.M.；
Edward,E.K.Bioorg.Med.Chem.Lett.2014,24,5015-5021；Li,G.；Wang,D.M.；Sun,M.N.；
Li,G.Y.；Hu,J.F.；Zhang,Y.,Yuan,Y.H.；Ji,H.J.；Chen,N.H.；Liu,G.J.Med.Chem.2010,
53,1741-1754.Application above documents disclose bridged piperazine derivatives in nonsteroidal anti-inflammatory drug field.
Splice principle using active skeleton, plays the collaboration anti-inflammatory activity of benzodioxan skeleton and piperazine skeleton, synthesis
Bridged piperazine derivatives based on benzodioxan skeleton simultaneously carry out research with preferable application prospect to its anti-inflammatory activity.At present also
Find no the report for the piperazine acidamide compound for closing the skeleton containing benzodioxan.
Invention content
A kind of the object of the present invention is to provide anti-inflammatory activities strong, the good skeleton containing benzodioxan of stability piperazine amide
Class compound；Present invention simultaneously provides preparation methods and application.
The piperazine acidamide compound of the skeleton of the present invention containing benzodioxan, structural formula are as follows：
Wherein R is with one of lower structure：
The preparation method of the piperazine acidamide compound of the skeleton of the present invention containing benzodioxan, including following step
Suddenly：
(1) Isosorbide-5-Nitrae-benzodioxan formylhydrazine is mixed with potassium hydroxide, methanol, carbon disulfide is added dropwise under ice-water bath, then
Back flow reaction is spin-dried for solvent, and water is added to filter, acidification of filtrate, obtains product a；
(2) substituent of piperazine, triethylamine and dichloromethane are mixed, chloracetyl chloride is added dropwise under ice-water bath, reacted, mistake
Filter, obtains product b；
(3) product a, product b, potassium hydroxide and methanol mixing, reaction are obtained into the piperazine acyl of the skeleton containing benzodioxan
Aminated compounds.
Wherein：
In step (1), Isosorbide-5-Nitrae-benzodioxan formylhydrazine, potassium hydroxide, carbon disulfide, methanol amount ratio be 1:1.2-
1.5:10:5-7, wherein Isosorbide-5-Nitrae-benzodioxan formylhydrazine, potassium hydroxide, carbon disulfide are in terms of mM number, and methanol is with milliliter
Meter.
In step (1), the time for adding of carbon disulfide is 15-20 minutes.
In step (1), reflux time is 8-10 hours.
In step (2), the substituent of piperazine, chloracetyl chloride, triethylamine, dichloromethane amount ratio be 1:1.2-1.5:
1.2-1.5:4, wherein the substituent of piperazine, chloracetyl chloride, triethylamine are in terms of mM number, and dichloromethane is in terms of milliliter.
In step (2), the substituent of piperazine is o-methoxyphenyl piperazine, m-methoxyphenyl piperazine, to methoxybenzene
Base piperazine, Chloro-O-Phenyl piperazine, chlorophenylpiperazine, o-fluorophenyl piperazine, 2- Pyridylpiperazines or m-trifluoromethylphenyl piperazine
One kind in piperazine.
In step (2), the time for adding of chloracetyl chloride is 3-5 minutes；Reaction time is 10-12 hours.
In step (3), product a, product b, potassium hydroxide, methanol amount ratio be 1:1:1.5:8, wherein product a, production
Object b, potassium hydroxide are in terms of mM number, and methanol is in terms of milliliter；Reaction time is 4-6 hours.
The piperazine acidamide compound of the skeleton of the present invention containing benzodioxan is used for the preparation of non-steroidal anti-inflammatory drugs.
The reaction equation of the present invention is as follows：
Wherein R is with one of lower structure：
Beneficial effects of the present invention are as follows：
The piperazine acidamide compound synthesis of the skeleton containing benzodioxan of the present invention is simple, Isosorbide-5-Nitrae-benzodioxan formyl
Hydrazine obtains benzodioxan mercapto derivatives with carbon disulfide annulation；In chloracetyl chloride the higher acid chloride of activity with singly take
Piperazine amide intermediate is obtained by nucleophilic substitution for unsubstituted amino in bridged piperazine derivatives；Piperazine amide intermediate
In α-chlorine then in benzodioxan mercapto derivatives sulfydryl occur nucleophilic substitution obtain bone containing benzodioxan
The piperazine acidamide compound of frame.The piperazine acidamide chemical combination of piperazine amide intermediate and the skeleton containing benzodioxan in the present invention
Object purification is simple, and yield is higher, and property stable in the air is good；Preparation method is simple and practicable, is suitble to industrialized production.In addition,
The present invention has preferable anti-inflammatory activity, can be used for the preparation of non-steroidal anti-inflammatory drugs.
Specific implementation mode
The present invention is described further with reference to embodiments.
Embodiment 1
2- (5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (4- (2- methoxybenzenes
Base) piperazine) ethyl ketone preparation, molecular formula is：
(1) 10mmol Isosorbide-5-Nitraes-benzodioxan formylhydrazine, 12mmol potassium hydroxide are dissolved in 50mL methanol, in ice-water bath
100mmol carbon disulfide is added dropwise, control drips off in 15 minutes, and after dripping carbon disulfide, back flow reaction 8 hours is spin-dried for molten
Agent is dissolved in water, filters, and filtrate adds hydrochloric acid to be acidified, and filtering obtains product a；
(2) 8mmol o-methoxyphenyls piperazine, 9.6mmol triethylamines are dissolved in 32mL dichloromethane, are delayed under condition of ice bath
Slow that 9.6mmol chloracetyl chlorides are added dropwise, control drips off in 3 minutes；It is stirred to react under condition of ice bath 10 hours, filters, produced
Object b；
(3) 4mmol products a, 4mmol products b, 6mmol potassium hydroxide is dissolved in 32mL methanol, and stirring at normal temperature is reacted 4 hours
After filter to obtain 2- (5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (4- (2- methoxybenzenes
Base) piperazine) ethyl ketone.
The compound is verified through nuclear-magnetism, mass spectrum, elemental analysis, the results showed that structure is correct, and data are as follows：
Nuclear-magnetism1H NMR(400MHz,CDCl3)δ：3.08 (s, 2H), 3.13 (s, 2H), 3.78 (s, 2H), 3.86 (s, 2H),
3.89 (s, 3H), 4.29-4.33 (m, 4H), 4.43 (s, 2H), 6.89-7.08 (m, 5H), 7.49-7.52 (m, 2H).
Mass spectrum ESI-MS：959.33([2M+Na]+)。
Elemental analysis Anal.Calcd for C23H24N4O5S：C,58.96；H,5.16；N,11.96.Found：C,
59.15；H,5.13；N, 12.01%.
Embodiment 2
2- (5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (4- (3- methoxybenzenes
Base) piperazine) ethyl ketone preparation, molecular formula is：
(1) 10mmol Isosorbide-5-Nitraes-benzodioxan formylhydrazine, 13mmol potassium hydroxide is dissolved in 60mL methanol, in ice-water bath
100mmol carbon disulfide is added dropwise, is dripped off in 18 minutes.After dripping carbon disulfide, back flow reaction 9 hours is spin-dried for solvent, adds water
Dissolving, filtering, filtrate add hydrochloric acid to be acidified, and filter, obtain product a；
(2) 8mmol m-methoxyphenyls piperazine, 11mmol triethylamines are dissolved in 32mL dichloromethane, are delayed under condition of ice bath
It is slow that 11mmol chloracetyl chlorides are added dropwise, it is dripped off in 4 minutes.It is stirred to react under condition of ice bath 11 hours, filters, obtain product b；
(3) 4mmol products a, 4mmol product b, 6mmol potassium hydroxide are dissolved in 32mL methanol, mistake after normal-temperature reaction 5 hours
Filter to obtain 2- (5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (4- (3- methoxyphenyls) piperazines
Piperazine) ethyl ketone.
The compound is verified through nuclear-magnetism, mass spectrum, elemental analysis, the results showed that structure is correct, and data are as follows：
Nuclear-magnetism1H NMR(400MHz,CDCl3)δ：3.16 (t, 2H), 3.29 (s, 2H), 3.81 (s, 5H), 3.88 (s, 2H),
4.29-4.34 (m, 4H), 4.39 (s, 2H), 6.50-6.59 (m, 3H), 6.95 (d, 1H), 7.21 (t, 1H), 7.48-7.52 (m,
2H)。
Mass spectrum ESI-MS：491.33([M+Na]+)。
Elemental analysis Anal.Calcd for C23H24N4O5S：C,58.96；H,5.16；N,11.96.Found：C,
58.78；H,5.14；N, 11.98%.
Embodiment 3
2- (5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (4- (4- methoxybenzenes
Base) piperazine) ethyl ketone preparation, molecular formula is：
(1) 10mmol Isosorbide-5-Nitraes-benzodioxan formylhydrazine, 15mmol potassium hydroxide is dissolved in 70mL methanol, in ice-water bath
100mmol carbon disulfide is added dropwise, is dripped off in 20 minutes.After dripping carbon disulfide, back flow reaction 10 hours is spin-dried for solvent, adds
Water dissolution, filtering, filtrate add hydrochloric acid to be acidified, and filtering obtains product a；
(2) 8mmol p-methoxyphenyls piperazine, 12mmol triethylamines are dissolved in 32mL dichloromethane, are delayed under condition of ice bath
It is slow that 12mmol chloracetyl chlorides are added dropwise, it is dripped off in 5 minutes.It is stirred to react under condition of ice bath 12 hours, filters, obtain product b；
(3) 4mmol products a, 4mmol product b, 6mmol potassium hydroxide are dissolved in 32mL methanol, mistake after normal-temperature reaction 6 hours
Filter to obtain 2- (5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (4- (4- methoxyphenyls) piperazines
Piperazine) ethyl ketone.
The compound is verified through nuclear-magnetism, mass spectrum, elemental analysis, the results showed that structure is correct, and data are as follows：
Nuclear-magnetism1H NMR(400MHz,CDCl3)δ：3.07 (t, 2H), 3.12 (t, 2H), 3.75 (t, 2H), 3.78 (s, 3H),
3.82 (t, 2H), 4.29-4.34 (m, 4H), 4.41 (s, 2H), 6.84-6.96 (m, 5H), 7.48-7.52 (m, 2H).
Mass spectrum ESI-MS:491.25([M+Na]+)。
Elemental analysis Anal.Calcd for C23H24N4O5S：C,58.96；H,5.16；N,11.96.Found：C,
59.20；H,5.14；N, 11.99%.
Embodiment 4
2- (5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (4- (2- chlorphenyls) piperazines
Piperazine) ethyl ketone preparation, molecular formula is：
O-methoxyphenyl piperazine in embodiment 1 is changed to Chloro-O-Phenyl piperazine, remaining step obtains 2- with embodiment 1
(5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (4- (2- chlorphenyls) piperazine) ethyl ketone.
The compound is verified through nuclear-magnetism, mass spectrum, elemental analysis, the results showed that structure is correct, and data are as follows：
Nuclear-magnetism1H NMR(400MHz,CDCl3)δ：2.25 (t, 2H), 3.15 (t, 2H), 3.81 (t, 2H), 3.84 (t, 2H),
4.31-4.35 (m, 4H), 4.44 (s, 2H), 6.97 (d, 2H), 7.04-7.06 (m, 2H), 7.41 (d, 1H), 7.51-7.54 (m,
2H)。
Mass spectrum ESI-MS:495.17([M+Na]+)。
Elemental analysis Anal.Calcd for C22H21ClN4O4S：C,55.87；H,4.48；N,11.85.Found：C,
56.09；H,4.46；N, 11.90%.
Embodiment 5
2- (5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (4- (2- fluorophenyls) piperazines
Piperazine) ethyl ketone preparation, molecular formula is：
O-methoxyphenyl piperazine in embodiment 1 is changed to o-fluorophenyl piperazine, remaining step obtains 2- with embodiment 1
(5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (4- (2- fluorophenyls) piperazine) ethyl ketone.
The compound is verified through nuclear-magnetism, mass spectrum, elemental analysis, the results showed that structure is correct, and data are as follows：
Nuclear-magnetism1H NMR(400MHz,CDCl3)δ：3.12 (t, 2H), 3.19 (t, 2H), 3.81 (t, 2H), 3.88 (t, 2H),
4.29-4.34 (m, 4H), 4.41 (s, 2H), 6.14-7.12 (m, 5H), 7.49-7.52 (m, 2H).
Mass spectrum ESI-MS:479.33([M+Na]+)
Elemental analysis Anal.Calcd for C22H21FN4O4S：C,57.88；H,4.64；N,12.27.Found：C,
58.05；H,4.62；N, 12.31%.
Embodiment 6
2- (5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (2- Pyridylpiperazines)
The preparation of ethyl ketone, molecular formula are：
2 intermediate methoxyphenylpiperazderivatives of embodiment are changed to 2- Pyridylpiperazines, remaining step obtains 2- with embodiment 2
(5- (2,3- dihydrobenzos [1,4] dioxanes) -1,3,4- oxadiazole -2- thioketones) -1- (2- Pyridylpiperazines) ethyl ketone.
The compound is verified through nuclear-magnetism, mass spectrum, elemental analysis, the results showed that structure is correct, and data are as follows：
Nuclear-magnetism1H NMR(400MHz,CDCl3)δ：3.49 (s, 2H), 3.75 (s, 4H), 3.82 (s, 2H), 4.35-4.33
(m, 4H), 4.40 (s, 2H), 6.70 (m, 2H), 6.95 (d, 2H), 7.51 (m, 3H).
Mass spectrum ESI-MS:901.17([2M+Na]+)。
Elemental analysis Anal.Calcd for C21H21N5O4S:C,57.39；H,4.82；N,15.94.Found：C,
57.60；H,4.80；N, 115.97%.
The character of the piperazine acidamide compound of the skeleton containing benzodioxan, yield, melting point data such as table in embodiment 1-6
1。
1 tables of data of table
| Serial number | Character | Yield (%) | Fusing point (DEG C) |
| Embodiment 1 | White powder | 75.5 | 171.0-172.5 |
| Embodiment 2 | White powder | 78.3 | 158.6-159.0 |
| Embodiment 3 | White powder | 76.3 | 197.1-198.3 |
| Embodiment 4 | Brown powder | 65.2 | 173.4-174.6 |
| Embodiment 5 | Brown powder | 82.3 | 154.1-155.5 |
| Embodiment 6 | Brown powder | 82.3 | 156.2-157.0 |
Embodiment 7
The anti-inflammatory activity of the piperazine acidamide compound of the skeleton containing benzodioxan in embodiment 1-6 is detected, is had
Steps are as follows for body：
18-22 grams of KM mouse adaptability is raised one week, and blank control group, positive controls and experimental group are randomly divided into,
Every group of 7 mouse.The preceding 20 hours all mouse of experiment are deprived of food but not water.Blank control group, positive controls and experimental group are small
Mouse gives the piperazine acyl of the skeleton containing benzodioxan in physiological saline, C14H10Cl2NNaO2 and embodiment 1-6 respectively in a manner of gavage
Aminated compounds.After gavage 1 hour, 40 microlitres of caused by dimethylbenzene xylene inflammation are uniformly smeared in mouse right ear two sides, left ear does not do any place
Reason.Mouse is taken off neck after 1 hour to put to death, ears is cut, the auricle at the same position of two ears is swept away with card punch, is claimed on assay balance
Weight, using the difference of same mouse or so auricle as swelling value.Swelling inhibiting rate=(the blank control group swelling value-administration group that is averaged is flat
Equal swelling value)/blank control group is averaged swelling value × 100%, data such as table 2.
The anti-inflammatory activity test result of 2 embodiment 1-6 of table, positive controls and blank control group
| Serial number | Swelling value (mg) | Swelling inhibiting rate (%) |
| Embodiment 1 | 4.34±0.24 | 68.02 |
| Embodiment 2 | 6.81±0.54 | 49.82 |
| Embodiment 3 | 5.83±0.74 | 57.04 |
| Embodiment 4 | 6.36±0.45 | 59.15 |
| Embodiment 5 | 6.79±0.70 | 49.96 |
| Embodiment 6 | 7.36±1.31 | 45.76 |
| Positive controls | 6.51±0.95 | 52.03 |
| Blank control group | 13.57±1.09 | — |
Claims (10)
1. a kind of piperazine acidamide compound of skeleton containing benzodioxan, it is characterised in that its structural formula is as follows：
Wherein R is with one of lower structure：
2. a kind of preparation method of the piperazine acidamide compound of the skeleton described in claim 1 containing benzodioxan, feature
It is to include the following steps：
(1) Isosorbide-5-Nitrae-benzodioxan formylhydrazine is mixed with potassium hydroxide, methanol, carbon disulfide is added dropwise under ice-water bath, then flow back
Reaction, is spin-dried for solvent, water is added to filter, acidification of filtrate obtains product a；
(2) substituent of piperazine, triethylamine and dichloromethane are mixed, chloracetyl chloride is added dropwise under ice-water bath, reacted, filtering obtains
To product b；
(3) product a, product b, potassium hydroxide and methanol mixing, reaction are obtained into the piperazine acidamide of the skeleton containing benzodioxan
Compound.
3. the preparation method of the piperazine acidamide compound of the skeleton according to claim 2 containing benzodioxan, feature
It is：In step (1), Isosorbide-5-Nitrae-benzodioxan formylhydrazine, potassium hydroxide, carbon disulfide, methanol amount ratio be 1:1.2-
1.5:10:5-7, wherein Isosorbide-5-Nitrae-benzodioxan formylhydrazine, potassium hydroxide, carbon disulfide by mM in terms of, methanol is with milliliter
Meter.
4. the preparation method of the piperazine acidamide compound of the skeleton according to claim 2 containing benzodioxan, feature
It is：In step (1), the time for adding of carbon disulfide is 15-20 minutes.
5. the preparation method of the piperazine acidamide compound of the skeleton according to claim 2 containing benzodioxan, feature
It is：In step (1), reflux time is 8-10 hours.
6. the preparation method of the piperazine acidamide compound of the skeleton according to claim 2 containing benzodioxan, feature
It is：In step (2), the substituent of piperazine, chloracetyl chloride, triethylamine, dichloromethane amount ratio be 1:1.2-1.5:1.2-
1.5:4, wherein the substituent of piperazine, chloracetyl chloride, triethylamine by mM in terms of, dichloromethane is in terms of milliliter.
7. the preparation method of the piperazine acidamide compound of the skeleton according to claim 2 containing benzodioxan, feature
It is：In step (2), the substituent of piperazine is o-methoxyphenyl piperazine, m-methoxyphenyl piperazine, p-methoxyphenyl piperazine
In piperazine, Chloro-O-Phenyl piperazine, chlorophenylpiperazine, o-fluorophenyl piperazine, 2- Pyridylpiperazines or m-trifluoromethyl phenylpiperazine
One kind.
8. the preparation method of the piperazine acidamide compound of the skeleton according to claim 2 containing benzodioxan, feature
It is：In step (2), the time for adding of chloracetyl chloride is 3-5 minutes；Reaction time is 10-12 hours.
9. the preparation method of the piperazine acidamide compound of the skeleton according to claim 2 containing benzodioxan, feature
It is：In step (3), product a, product b, potassium hydroxide, methanol amount ratio be 1:1:1.5:8, wherein product a, product b,
Potassium hydroxide by mM in terms of, methanol is in terms of milliliter；Reaction time is 4-6 hours.
10. a kind of application of the piperazine acidamide compound of the skeleton described in claim 1 containing benzodioxan, feature exist
In：Preparation for non-steroidal anti-inflammatory drugs.
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| CN114751868A (en) * | 2022-04-22 | 2022-07-15 | 山东理工大学 | Diaryl-substituted triazole acetic acid compound and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114751868A (en) * | 2022-04-22 | 2022-07-15 | 山东理工大学 | Diaryl-substituted triazole acetic acid compound and preparation method and application thereof |
| CN114751868B (en) * | 2022-04-22 | 2024-04-12 | 山东理工大学 | Diaryl substituted triazole acetic acid compound, and preparation method and application thereof |
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