CN108341807B - Piperazine amide compound containing benzodioxane skeleton and preparation method and application thereof - Google Patents
Piperazine amide compound containing benzodioxane skeleton and preparation method and application thereof Download PDFInfo
- Publication number
- CN108341807B CN108341807B CN201810129153.4A CN201810129153A CN108341807B CN 108341807 B CN108341807 B CN 108341807B CN 201810129153 A CN201810129153 A CN 201810129153A CN 108341807 B CN108341807 B CN 108341807B
- Authority
- CN
- China
- Prior art keywords
- piperazine
- amide compound
- product
- piperazine amide
- benzodioxane
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of non-steroidal anti-inflammatory drugs, and particularly relates to a piperazine amide compound containing benzodioxane skeleton, and a preparation method and application thereof. The piperazine amide compound containing the benzodioxane skeleton is prepared by mixing 1, 4-benzodioxane formylhydrazine, potassium hydroxide and methanol, dripping carbon disulfide in an ice water bath, performing reflux reaction, spin-drying a solvent, adding water, filtering, and acidifying filtrate to obtain a product a; mixing a substitute of piperazine, triethylamine and dichloromethane, dropwise adding chloroacetyl chloride in an ice water bath, reacting, and filtering to obtain a product b; and mixing the product a, the product b, potassium hydroxide and methanol, and reacting to obtain the catalyst. The piperazine amide compound containing the benzodioxane skeleton is simple to synthesize, convenient to purify, high in yield and good in stability in air; the preparation method is simple and feasible, and is suitable for industrial production. In addition, the invention has better anti-inflammatory activity and can be used for preparing non-steroidal anti-inflammatory drugs.
Description
Technical Field
The invention belongs to the technical field of non-steroidal anti-inflammatory drugs, and particularly relates to a piperazine amide compound containing benzodioxane skeleton, and a preparation method and application thereof.
Background
Inflammation is a self-defense mechanism of the body against infection, and is mainly manifested by red swelling, edema, pain, fever, and the like. Non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, ibuprofen, naproxen, and fenbufen, are the first-line drugs most commonly used clinically to treat inflammation. According to incomplete statistics, 1 hundred million people use the medicine all over the world. The problem of adverse reactions and side effects of NSAIDs is also prominent as first-line drugs for anti-inflammatory and analgesic use. Therefore, the research and development of the non-steroidal anti-inflammatory drug with high efficiency and small side effect has important significance.
The benzodioxan backbone has a very broad biological activity, and molecular design and synthetic process studies of this class of compounds have been the focus of interest, such as those disclosed in Sun, J.; Wang, S.; Sheng, G.H.; L ian, Z.M.; L iu, 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.; Rafaani, G.; Carrieri, A.; Amantini, C.; L mediali, R.; Santoni G.; Poesi E.; E. L eonardi, A.J.2008. J.2008. 9, J.59. J.9, J.9. Shield Bulll., U.S.J.487 to No. J.9, and U.S.A. J.A. 5, and No. J.11, J.P.P.P.A. D. 5, to disclose the use of the aforementioned steroid.
Piperazine derivatives have attracted much attention because of their various biological activities, such as Khaled, r.r., abdellifa, a.m., Edward, e.g., anti-cancer, anti-bacterial, anti-depression, anti-hypertension, anti-inflammatory and analgesic activities, such as L et.2014, 24, 5015-.
By utilizing the active framework splicing principle, the synergistic anti-inflammatory activity of the benzodioxane framework and the piperazine framework is exerted, the piperazine derivative based on the benzodioxane framework is synthesized, and the anti-inflammatory activity of the piperazine derivative is researched, so that the piperazine derivative has a good application prospect. No reports on piperazine amide compounds containing a benzodioxane skeleton have been found.
Disclosure of Invention
The invention aims to provide a piperazine amide compound containing a benzodioxane skeleton, which has strong anti-inflammatory activity and good stability; the invention also provides a preparation method and application thereof.
The piperazine amide compound containing the benzodioxane skeleton has the following structural formula:
wherein R is one of the following structures:
the preparation method of the piperazine amide compound containing the benzodioxane skeleton comprises the following steps:
(1) mixing 1, 4-benzodioxan formyl hydrazine, potassium hydroxide and methanol, dripping carbon disulfide in an ice-water bath, performing reflux reaction, spin-drying a solvent, adding water, filtering, and acidifying filtrate to obtain a product a;
(2) mixing a substitute of piperazine, triethylamine and dichloromethane, dropwise adding chloroacetyl chloride in an ice water bath, reacting, and filtering to obtain a product b;
(3) and mixing the product a, the product b, potassium hydroxide and methanol, and reacting to obtain the piperazine amide compound containing the benzodioxane skeleton.
Wherein:
in the step (1), the dosage ratio of the 1, 4-benzodioxan formyl hydrazine, the potassium hydroxide, the carbon disulfide and the methanol is 1:1.2-1.5:10:5-7, wherein the 1, 4-benzodioxan formyl hydrazine, the potassium hydroxide and the carbon disulfide are counted in millimole, and the methanol is counted in milliliter.
In the step (1), the dropping time of the carbon disulfide is 15-20 minutes.
In the step (1), the reflux reaction time is 8-10 hours.
In the step (2), the dosage ratio of the substituent of piperazine, chloracetyl chloride, triethylamine and dichloromethane is 1:1.2-1.5:1.2-1.5:4, wherein the substituent of piperazine, chloracetyl chloride and triethylamine are calculated by millimole, and the dichloromethane is calculated by milliliter.
In the step (2), the substitute of piperazine is one of o-methoxyphenylpiperazine, m-methoxyphenylpiperazine, p-methoxyphenylpiperazine, o-chlorophenylpiperazine, m-chlorophenylpiperazine, o-fluorophenylpiperazine, 2-pyridylpiperazine or m-trifluoromethylphenylpiperazine.
In the step (2), the dripping time of the chloracetyl chloride is 3-5 minutes; the reaction time is 10-12 hours.
In the step (3), the using amount ratio of the product a to the product b to the potassium hydroxide to the methanol is 1:1:1.5:8, wherein the product a, the product b and the potassium hydroxide are calculated by millimoles, and the methanol is calculated by milliliter; the reaction time is 4-6 hours.
The piperazine amide compound containing the benzodioxane skeleton is used for preparing the non-steroidal anti-inflammatory drug.
The reaction equation of the present invention is as follows:
wherein R is one of the following structures:
the invention has the following beneficial effects:
the piperazine amide compound containing the benzodioxane skeleton is simple to synthesize, 1, 4-benzodioxane formylhydrazine and carbon disulfide are subjected to cyclization reaction to obtain a benzodioxane sulfydryl derivative, acyl chloride with higher activity in chloroacetyl chloride and unsubstituted amino in the monosubstituted piperazine derivative are subjected to nucleophilic substitution reaction to obtain a piperazine amide intermediate, and α -chloride in the piperazine amide intermediate is subjected to nucleophilic substitution reaction with sulfydryl in the benzodioxane sulfydryl derivative to obtain the piperazine amide compound containing the benzodioxane skeleton.
Detailed Description
The present invention is further described below with reference to examples.
Example 1
Preparation of 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thione) -1- (4- (2-methoxyphenyl) piperazine) ethanone, its molecular formula is:
(1) dissolving 10mmol of 1, 4-benzodioxan formyl hydrazine and 12mmol of potassium hydroxide in 50m L methanol, dropwise adding 100mmol of carbon disulfide in an ice water bath, controlling the dropwise addition within 15 minutes, carrying out reflux reaction for 8 hours after the carbon disulfide is dropwise added, spin-drying a solvent, adding water for dissolution, filtering, adding hydrochloric acid into a filtrate for acidification, and filtering to obtain a product a;
(2) dissolving 8mmol of o-methoxyphenyl piperazine and 9.6mmol of triethylamine in 32m L dichloromethane, slowly dropwise adding 9.6mmol of chloroacetyl chloride under the ice bath condition, controlling the dropwise adding within 3 minutes, stirring under the ice bath condition for reaction for 10 hours, and filtering to obtain a product b;
(3)4mmol of the product a, 4mmol of the product b and 6mmol of potassium hydroxide are dissolved in 32m L methanol, stirred at normal temperature, reacted for 4 hours and then filtered to obtain the 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thione) -1- (4- (2-methoxyphenyl) piperazine) ethanone.
The compound is verified by nuclear magnetism, mass spectrum and element analysis, and the result shows that the compound has a correct structure, and the data is as follows:
nuclear magnetism1H NMR(400MHz,CDCl3)：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％。
Example 2
Preparation of 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thione) -1- (4- (3-methoxyphenyl) piperazine) ethanone, its molecular formula is:
(1) dissolving 10mmol of 1, 4-benzodioxan formyl hydrazine and 13mmol of potassium hydroxide in 60m L methanol, dropwise adding 100mmol of carbon disulfide in an ice water bath, completing dropwise addition within 18 minutes, performing reflux reaction for 9 hours after completing dropwise addition of the carbon disulfide, spin-drying a solvent, adding water for dissolution, filtering, adding hydrochloric acid into filtrate for acidification, and filtering to obtain a product a;
(2)8mmol of m-methoxyphenyl piperazine and 11mmol of triethylamine are dissolved in 32m L dichloromethane, 11mmol of chloroacetyl chloride is slowly dripped under the ice bath condition, the dripping is finished within 4 minutes, the mixture is stirred and reacts for 11 hours under the ice bath condition, and the product b is obtained after filtration;
(3)4mmol of the product a, 4mmol of the product b, 6mmol of potassium hydroxide are dissolved in 32m L methanol, reacted for 5 hours at normal temperature and filtered to obtain the 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thioketone) -1- (4- (3-methoxyphenyl) piperazine) ethanone.
The compound is verified by nuclear magnetism, mass spectrum and element analysis, the result shows that the structure is correct, and the data is as follows:
nuclear magnetism1H NMR(400MHz,CDCl3)：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％。
Example 3
Preparation of 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thione) -1- (4- (4-methoxyphenyl) piperazine) ethanone, its molecular formula is:
(1) dissolving 10mmol of 1, 4-benzodioxan formyl hydrazine and 15mmol of potassium hydroxide in 70m L methanol, dropwise adding 100mmol of carbon disulfide in an ice water bath, completing dropwise addition within 20 minutes, performing reflux reaction for 10 hours after completing dropwise addition of the carbon disulfide, spin-drying a solvent, adding water for dissolution, filtering, adding hydrochloric acid into filtrate for acidification, and filtering to obtain a product a;
(2)8mmol of p-methoxyphenyl piperazine and 12mmol of triethylamine are dissolved in 32m L dichloromethane, 12mmol of chloroacetyl chloride is slowly dripped under the ice bath condition, the dripping is finished within 5 minutes, the mixture is stirred and reacts for 12 hours under the ice bath condition, and the product b is obtained after filtration;
(3)4mmol of the product a, 4mmol of the product b, 6mmol of potassium hydroxide are dissolved in 32m L methanol, reacted for 6 hours at normal temperature and filtered to obtain the 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thioketone) -1- (4- (4-methoxyphenyl) piperazine) ethanone.
The compound is verified by nuclear magnetism, mass spectrum and element analysis, the result shows that the structure is correct, and the data is as follows:
nuclear magnetism1H NMR(400MHz,CDCl3)：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 Spectrometry 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％。
Example 4
Preparation of 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thione) -1- (4- (2-chlorophenyl) piperazine) ethanone of the formula:
the o-methoxyphenylpiperazine was changed to o-chlorophenylpiperazine in example 1, and the rest of the procedure was the same as in example 1, to give 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thione) -1- (4- (2-chlorophenyl) piperazine) ethanone.
The compound is verified by nuclear magnetism, mass spectrum and element analysis, the result shows that the structure is correct, and the data is as follows:
nuclear magnetism1H NMR(400MHz,CDCl3)：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 Spectrometry 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％。
Example 5
Preparation of 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thione) -1- (4- (2-fluorophenyl) piperazine) ethanone of the formula:
the o-methoxyphenylpiperazine of example 1 was changed to o-fluorophenylpiperazine, and the remaining steps were the same as in example 1, to give 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thione) -1- (4- (2-fluorophenyl) piperazine) ethanone.
The compound is verified by nuclear magnetism, mass spectrum and element analysis, the result shows that the structure is correct, and the data is as follows:
nuclear magnetism1H NMR(400MHz,CDCl3)：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 Spectrometry 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％。
Example 6
Preparation of 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thione) -1- (2-pyridylpiperazine) ethanone of the formula:
the intermediate methoxyphenylpiperazine of example 2 was changed to 2-pyridylpiperazine, and the remaining steps were the same as in example 2 to give 2- (5- (2, 3-dihydrobenzo [1,4] dioxane) -1,3, 4-oxadiazole-2-thione) -1- (2-pyridylpiperazine) ethanone.
The compound is verified by nuclear magnetism, mass spectrum and element analysis, the result shows that the structure is correct, and the data is as follows:
nuclear magnetism1H NMR(400MHz,CDCl3)：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 Spectrometry 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 properties, yield and melting point data of the piperazine amide compounds containing benzodioxane skeleton in examples 1 to 6 are shown in table 1.
TABLE 1 data sheet
| Serial number | Traits | Yield (%) | Melting Point (. degree.C.) |
| Example 1 | White powder | 75.5 | 171.0-172.5 |
| Example 2 | White powder | 78.3 | 158.6-159.0 |
| Example 3 | White powder | 76.3 | 197.1-198.3 |
| Example 4 | Brown powder | 65.2 | 173.4-174.6 |
| Example 5 | Brown powder | 82.3 | 154.1-155.5 |
| Example 6 | Brown powder | 82.3 | 156.2-157.0 |
Example 7
The anti-inflammatory activity of the piperazine amide compounds containing benzodioxane skeletons in examples 1 to 6 was examined by the following specific steps:
18-22 g of KM mice were adaptively maintained for one week and randomly divided into a blank control group, a positive control group and an experimental group, each group consisting of 7 mice, all the mice were fasted without water for 20 hours before the experiment, the mice in the blank control group, the positive control group and the experimental group were administered with physiological saline, diclofenac sodium and the piperazine amide compound containing a benzodioxane skeleton of examples 1-6, respectively, by gavage, after 1 hour of gavage, 40. mu.l of xylene was evenly applied to both sides of the right ear of the mice to cause inflammation, the left ear was not treated, after 1 hour, the mice were decapped, both ears were cut, the ear pieces of the same part of both ears were punched out with a punch, and the mice were weighed on an analytical balance, and the difference between the left and right ear pieces of the same mice was used as a swelling value (average swelling value of the blank control group-average swelling value of the administration group)/average swelling value of the blank control group × 100%, and the data are shown in Table 2.
TABLE 2 anti-inflammatory Activity test results for examples 1-6, positive control and blank control
| Serial number | Swelling number (mg) | Swelling inhibition ratio (%) |
| Example 1 | 4.34±0.24 | 68.02 |
| Example 2 | 6.81±0.54 | 49.82 |
| Example 3 | 5.83±0.74 | 57.04 |
| Example 4 | 6.36±0.45 | 59.15 |
| Example 5 | 6.79±0.70 | 49.96 |
| Example 6 | 7.36±1.31 | 45.76 |
| Positive control group | 6.51±0.95 | 52.03 |
| Blank control group | 13.57±1.09 | — |
Claims (10)
1. A piperazine amide compound containing benzodioxane skeleton is characterized in that the structural formula is as follows:
wherein R is one of the following structures:
performing cyclization reaction on the 1, 4-benzodioxan formyl hydrazine and carbon disulfide to obtain a benzodioxan sulfydryl derivative;
carrying out nucleophilic substitution reaction on acyl chloride with higher activity in chloroacetyl chloride and unsubstituted amino in the monosubstituted piperazine derivative to obtain a piperazine amide intermediate;
α -chlorine in the piperazine amide intermediate and mercapto in the benzodioxan mercapto derivative are subjected to nucleophilic substitution reaction to obtain the piperazine amide compound containing the benzodioxan skeleton.
2. A method for producing a piperazine amide compound containing a benzodioxane skeleton according to claim 1, comprising the steps of:
(1) mixing 1, 4-benzodioxan formyl hydrazine, potassium hydroxide and methanol, dripping carbon disulfide in an ice-water bath, performing reflux reaction, spin-drying a solvent, adding water, filtering, and acidifying filtrate to obtain a product a;
(2) mixing a substitute of piperazine, triethylamine and dichloromethane, dropwise adding chloroacetyl chloride in an ice water bath, reacting, and filtering to obtain a product b;
(3) and mixing the product a, the product b, potassium hydroxide and methanol, and reacting to obtain the piperazine amide compound containing the benzodioxane skeleton.
3. The method for producing a piperazine amide compound having a benzodioxane skeleton according to claim 2, wherein: in the step (1), the dosage ratio of the 1, 4-benzodioxan formyl hydrazine, the potassium hydroxide, the carbon disulfide and the methanol is 1:1.2-1.5:10:5-7, wherein the 1, 4-benzodioxan formyl hydrazine, the potassium hydroxide and the carbon disulfide are calculated by millimole, and the methanol is calculated by milliliter.
4. The method for producing a piperazine amide compound having a benzodioxane skeleton according to claim 2, wherein: in the step (1), the dropping time of the carbon disulfide is 15-20 minutes.
5. The method for producing a piperazine amide compound having a benzodioxane skeleton according to claim 2, wherein: in the step (1), the reflux reaction time is 8-10 hours.
6. The method for producing a piperazine amide compound having a benzodioxane skeleton according to claim 2, wherein: in the step (2), the dosage ratio of the substituent of piperazine, chloracetyl chloride, triethylamine and dichloromethane is 1:1.2-1.5:1.2-1.5:4, wherein the substituent of piperazine, chloracetyl chloride and triethylamine are calculated by millimole, and the dichloromethane is calculated by milliliter.
7. The method for producing a piperazine amide compound having a benzodioxane skeleton according to claim 2, wherein: in the step (2), the substitute of piperazine is one of o-methoxyphenylpiperazine, m-methoxyphenylpiperazine, p-methoxyphenylpiperazine, o-chlorophenylpiperazine, m-chlorophenylpiperazine, o-fluorophenylpiperazine, 2-pyridylpiperazine or m-trifluoromethylphenylpiperazine.
8. The method for producing a piperazine amide compound having a benzodioxane skeleton according to claim 2, wherein: in the step (2), the dripping time of the chloracetyl chloride is 3-5 minutes; the reaction time is 10-12 hours.
9. The method for producing a piperazine amide compound having a benzodioxane skeleton according to claim 2, wherein: in the step (3), the using amount ratio of the product a to the product b to the potassium hydroxide to the methanol is 1:1:1.5:8, wherein the product a, the product b and the potassium hydroxide are calculated by millimoles, and the methanol is calculated by milliliters; the reaction time is 4-6 hours.
10. The use of the benzodioxane skeleton-containing piperazine amide compound according to claim 1, wherein: is used for preparing the non-steroidal anti-inflammatory drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810129153.4A CN108341807B (en) | 2018-02-08 | 2018-02-08 | Piperazine amide compound containing benzodioxane skeleton and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810129153.4A CN108341807B (en) | 2018-02-08 | 2018-02-08 | Piperazine amide compound containing benzodioxane skeleton and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108341807A CN108341807A (en) | 2018-07-31 |
| CN108341807B true CN108341807B (en) | 2020-07-28 |
Family
ID=62958730
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810129153.4A Active CN108341807B (en) | 2018-02-08 | 2018-02-08 | Piperazine amide compound containing benzodioxane skeleton and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108341807B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE271045T1 (en) * | 1998-09-03 | 2004-07-15 | Kyowa Hakko Kogyo Kk | OXYGEN-CONTAINING HETEROCYCLIC COMPOUNDS |
| CN102690261B (en) * | 2011-03-25 | 2015-02-25 | 南京大学 | Preparation method of 1,4-benzodioxan-containing 1,3,4-oxadiazole derivatives and use of the 1,4-benzdioxan-containing 1,3,4-oxadiazole derivatives in anti-cancer drugs |
| CN103087053A (en) * | 2011-11-03 | 2013-05-08 | 南京大学 | Preparation of oxadiazole compound and application thereof to anti-inflammatory treatment |
| CN103382204B (en) * | 2013-04-07 | 2016-03-23 | 南京农业大学 | Containing the preparation method and its usage of 1,3,4-oxadiazole derivative of benzo Isosorbide-5-Nitrae-Evil dioxane |
| CN104292224B (en) * | 2014-09-24 | 2016-07-06 | 贵州大学 | Containing replacing 1,3,4-thiophene () diazole thioether benzothiazole amide derivatives and its preparation method and application |
| CN105777731B (en) * | 2016-04-22 | 2018-10-16 | 山东理工大学 | The bridged piperazine derivatives and its preparation method and application of Han You oxadiazoles |
-
2018
- 2018-02-08 CN CN201810129153.4A patent/CN108341807B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN108341807A (en) | 2018-07-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3920918A1 (en) | Methods and compositions for modulating splicing | |
| CN107033087B (en) | 1H-indazole-4-amine compounds and use thereof as IDO inhibitors | |
| WO2020163544A1 (en) | Methods and compositions for modulating splicing | |
| JP2022521467A (en) | Methods and compositions for regulating splicing | |
| CN104557588B (en) | Caffeic acid and the homodimer of ferulic acid, its preparation method and pharmaceutical composition thereof | |
| CN101289481A (en) | Synthesis of N-aryl-3-(4-beta-D-allopyranoside phenyl)-5-formyl isoxazole-4-methane amide | |
| JP2012514018A (en) | Toluidine sulfonamides and their use | |
| JP2012514019A (en) | Toluidinesulfonamides and their use as inhibitors | |
| CN104592195A (en) | A preparing process of alogliptin benzoate | |
| CN108341807B (en) | Piperazine amide compound containing benzodioxane skeleton and preparation method and application thereof | |
| CN104080335B (en) | Some chemical entities, composition and method | |
| CN111018738B (en) | Paeonol derivative, pharmaceutical preparation, preparation method and application | |
| TWI834819B (en) | Methods of making high enantioselective secondary alcohols | |
| CN108358928A (en) | A kind of preparation method of (6S) -5-methyltetrahydrofolate calcium | |
| WO2004087164A1 (en) | 8-nitro-tryptanthrin and other tryptanthrin derivatives used for the treatment of diseases caused by highly proliferating cells | |
| CN116284018A (en) | Preparation method and application of furo [2,3-b ] quinoline derivative | |
| CN113493374B (en) | SIRT1 receptor agonist and medicine containing same | |
| CN102060875B (en) | Quinazoline derivative, and preparation method and application thereof | |
| CN102875499B (en) | The preparation method of 3-aminomethyl trimethylene oxide and organic acid salt thereof | |
| CN100567304C (en) | Methylsulfonic acid 10-O-(dimethyl amido ethyl) Ginkgolide B semihydrate crystal and preparation method thereof | |
| CN115710253B (en) | Aminobenzimidazole-containing derivatives, and preparation and application thereof | |
| WO2014046224A1 (en) | Coumarin derivative | |
| CN113277980B (en) | Tolvaptan impurity and preparation method thereof | |
| JPH02502728A (en) | N-naphthoylglycine as an aldose reductase inhibitor | |
| TW201245197A (en) | Substituted [(5h-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)piperazin-1-yl]-2,2-dimethylpropanoic acid compounds as dual activity H1 inverse agonists/5-HT2A antagonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |