CN104926838A - 5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative and application - Google Patents
5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative and application Download PDFInfo
- Publication number
- CN104926838A CN104926838A CN201510286939.3A CN201510286939A CN104926838A CN 104926838 A CN104926838 A CN 104926838A CN 201510286939 A CN201510286939 A CN 201510286939A CN 104926838 A CN104926838 A CN 104926838A
- Authority
- CN
- China
- Prior art keywords
- triazole
- phenyl
- thiazine
- chloro
- fluorophenyl
- 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
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a 5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative with a general formula I, or a pharmaceutically acceptable aquo-complex and salts of the derivative; the derivative comprises a stereisomer or a tautomer, wherein R1 and R2 in the formula I are respectively independent hydrogen, methyl, halogen, hydroxyl, methoxyl, acetyl, propiono, nitro or alkoxy. The 5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative has an obvious inhibiting effect on acetylcholin esterase, and is used for improving the memory of a patient suffering from dementia and Alzheimer's disease. The invention also relates to a preparation method of the compound and an application in preparation of a drug for treating Senile Dementia.
Description
Technical field
The invention belongs to medical art, particularly relate to 5H-[1,2,4] triazole also [5,1-b] [1,3] thiazide derivative and preparation method thereof with as acetylcholinesterase depressant, for improving the application suffered from dull-witted and Alzheimer's disease patient and remember.
Background technology
Alzheimer is relevant with the degeneration of the cholinergic neuron in basal forebrain.Due to the result of described degeneration, the patient suffering from this disease shows obvious decay in vagusstoff synthesis, choline acetyltransferase activity, acetylcholine esterase active and choline absorption.
Known acetylcholinesterase depressant is effective in raising cholinergic activity, therefore can be used for the memory improving Alzheimer patients.By acetylcholine esterase inhibition, described compound can improve the level of neurotransmission transmitter acetylcholine in brain, therefore can hypermnesis.
Existing acetylcholinesterase depressant is as tacrine, and this bright, lycoremine etc., still exist resistance or pharmacokinetic deficits.Compound of the present invention, as the acetylcholinesterase depressant of brand new type, has structure type novelty, and drug action and existing medicine quite or be better than the feature of existing medicine, have good using value and development prospect.
Summary of the invention
The object of the present invention is to provide a kind of 5H-[1,2,4] triazole also [5,1-b] [1,3] thiazides analog derivative, it has good inhibiting activity of acetylcholinesterase.
Above-mentioned purpose of the present invention is achieved by the following technical solution:
A kind of acetylcholinesterase depressant, there is the effect strengthening dull-witted and Alzheimer's disease memory in patients, it is characterized in that: this compound is the 5H-[1 with general formula I, 2,4] triazole also [5,1-b] [1,3] thiazide derivative or the acceptable hydrate of its pharmacy, salt, comprise its steric isomer or tautomer;
Wherein, the R in formula I
1, R
2independently be hydrogen, methyl, halogen, hydroxyl, methoxyl group, ethanoyl, propionyl, nitro or alkoxyl group.
Compound according to claim 1, is characterized in that: described R
1for fluorine.
Compound according to claim 1, is characterized in that: described R
2for chlorine.
Compound according to claim 1, is characterized in that: described R
2for 2-(piperidino) oxyethyl group.
The term " halogen " applied in the present invention comprises fluorine, chlorine or bromine.
Present invention also offers the purposes of above-claimed cpd for the preparation for the treatment of senile dementia.
" pharmacy acceptable salt " refers to the biopotency and the character that remain type I compound, and with the acid of suitable non-toxic organic or inorganic or the conventional acid addition salts that formed of organic or inorganic alkali or base addition salt.The example of acid salt comprises acetate, adipate, alginate, aspartate, benzoate, benzene sulfonate, hydrosulfate, butyrates, Citrate trianion, camphorate, camsilate, cipionate, digluconate, dodecyl sulfate, esilate, fumarate, gluceptate, glycerophosphate, Hemisulphate, enanthate, hexanoate, hydrogen chlorate, hydrobromate, hydriodate, 2-isethionate, lactic acid salt, maleate, mesylate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinic acid salt, persulphate, 3-phenylpropionic acid salt, picrate, Pivalate, propionic salt, succinate, vitriol, tartrate, thiocyanate-, tosylate and undecylate.Alkali salt comprises ammonium salt, an alkali metal salt, such as sodium and sylvite, alkaline earth salt, such as calcium and magnesium salts, the salt of organic bases, such as dicyclohexyl amine salt, N-methyl-D-glucamine salt, and amino acid whose salt, such as arginine, Methionin etc., and, Basic nitrogen-containing groups can be quaternized with such reagent, and such as elementary alkyl halide, as methyl, ethyl, the chlorine of propyl group and butyl, bromine and iodide; Dialkyl sulfate, as methyl-sulfate, diethyl ester, dibutylester and diamyl ester; Long chain halide, as decyl, lauryl, the chlorine of myristyl and stearyl-, bromine and iodide; Aralkyl halide, as the bromide etc. of benzyl and styroyl.The acid being preferred for generating acid salt comprises hydrochloric acid and acetic acid.
Present invention also offers the preparation method of above-mentioned compound of Formula I, the method is shown in following formula.
Present system research and illustrate structure and the preparation of described compound, described compound is as the new acetylcholinesterase depressant of a class, and structure type is novel, for development of new anti-senile dementia disease drug provides brand-new direction and wide platform.
Embodiment
Embodiment 1
The preparation of 5-(4-fluorophenyl)-3-sulfydryl-1,2,4-triazole
In 250 mL there-necked flasks, add thiosemicarbazide 9.1g (0.1 mo1), methylene dichloride 100 mL, ice-water bath stirring and dissolving, then add pyridine 10.3g (0.13 mo1).Slowly drip 4-fluorobenzoyl chloride 20.6g (0.13mo1) at 0-5 DEG C, 20 min dropwise, and 15 DEG C of reaction 2 h, terminate reaction.System has a large amount of white solid to occur, filters.Gained white solid is dissolved in the sodium hydroxide solution of 80 mL massfractions 5%, reflux 2h, is down to room temperature, adjusts pH to 5-6 with the dilute hydrochloric acid of massfraction 3.65%, a large amount of light yellow solid is had to separate out, filter, recrystallization, obtains 5-(4-fluorophenyl)-3-sulfydryl-1,2,4-triazole 17.2 g, yield 88.2%, ESI-MS (m/z): 196.2 (M+H)
+.
Embodiment 2
The preparation of 5-(4-chloro-phenyl-)-3-sulfydryl-1,2,4-triazole
Thiosemicarbazide 9.1g (0.1 mo1), methylene dichloride 100 mL, pyridine 10.3g (0.13 mo1) and 4-chloro-benzoyl chloride 22.75g (0.13mo1) is according to embodiment 1 method, obtain 5-(4-chloro-phenyl-)-3-sulfydryl-1,2,4-triazole 18.3g, yield 86.7%, ESI-MS (m/z): 212.3 (M+H)
+.
Embodiment 3
The preparation of 2-(4-fluorophenyl)-7-(4 chloro-phenyl-)-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L1)
By 5-(4-fluorophenyl)-3-sulfydryl-1,2,4-triazole 1.95g (0.01 mol) and 4 '-chloro-3-brom-acetophenone 2.47g (0.01mol), add 50 mL acetic acid, after back flow reaction 3h, TLC monitoring reaction completes, be cooled to room temperature, reaction solution separates out solid gradually, suction filtration, after water washing, ethyl alcohol recrystallization, obtain white crystal 2.15 grams, yield 62.73%.
1H-NMR(300MHz，DMSO)，δ(ppm)：3.61(H，d)，6.40(H，t)，7.30 (2H，d，
J=8.4Hz)，7.34(2H，d，
J=8.4Hz)，7.44(2H，d，
J=8.4Hz)，7.77(2H，d，
J=8.4Hz)； ESI-MS (m/z)：344.1 (M+H)
+。
Embodiment 4
The preparation of 2-(4-fluorophenyl)-7-(4-fluorophenyl)-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L2)
By 5-(4-fluorophenyl)-3-sulfydryl-1,2,4-triazole 1.95g (0.01 mol) and 4 '-fluoro-3-brom-acetophenone 2.31g (0.01mol), add 50 mL acetic acid, after back flow reaction 3h, TLC monitoring reaction completes, be cooled to room temperature, reaction solution separates out solid gradually, suction filtration, after water washing, ethyl alcohol recrystallization, obtain white crystal 2.08 grams, yield 63.41%.
1H-NMR(300MHz，DMSO)，δ(ppm)：3.60(H，d)，6.41(H，t)，7.19 (2H，d，
J=8.4Hz)，7.30(2H，d，
J=8.4Hz)，7.36(2H，d，
J=8.4Hz)，7.76(2H，d，
J=8.4Hz)； ESI-MS (m/z)：328.1 (M+H)
+。
Embodiment 5
The preparation of 2-(4-fluorophenyl)-7-(4-p-methoxy-phenyl)-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L3)
By 5-(4-fluorophenyl)-3-sulfydryl-1,2,4-triazole 1.95g (0.01 mol) and 4 '-methoxyl group-3-brom-acetophenone 2.43g (0.01mol), add 50 mL acetic acid, after back flow reaction 3h, TLC monitoring reaction completes, be cooled to room temperature, reaction solution separates out solid gradually, suction filtration, after water washing, ethyl alcohol recrystallization, obtain white crystal 2.11 grams, yield 62.05%.
1H-NMR(300MHz，DMSO)，δ(ppm)：3.60(H，d)，3.83(3H，s)，6.41(H，t)，6.84 (2H，d，
J=8.4Hz)，7.27(2H，d，
J=8.4Hz)，7.32(2H，d，
J=8.4Hz)，7.76(2H，d，
J=8.4Hz)； ESI-MS (m/z)：340.2 (M+H)
+。
Embodiment 6
The preparation of 2-(4-fluorophenyl)-7-(4-hydroxy phenyl)-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L4)
By 5-(4-fluorophenyl)-3-sulfydryl-1,2,4-triazole 1.95g (0.01 mol) and 4 '-hydroxyl-3-brom-acetophenone 2.29g (0.01mol), add 50 mL acetic acid, after back flow reaction 3h, TLC monitoring reaction completes, be cooled to room temperature, reaction solution separates out solid gradually, suction filtration, after water washing, ethyl alcohol recrystallization, obtain white crystal 2.29 grams, yield 70.46%.
1H-NMR(300MHz，DMSO)，δ(ppm)：3.60(H，d)，6.41(H，t)，6.68 (2H，d，
J=8.4Hz)，7.21(2H，d，
J=8.4Hz)，7.36(2H，d，
J=8.4Hz)，7.78(2H，d，
J=8.4Hz)，8.60(H，s)； ESI-MS (m/z)：326.1 (M+H)
+。
Embodiment 7
2-(4-fluorophenyl)-7-{4-[2-(piperidino) oxyethyl group] phenyl } preparation of-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L5)
By 5-(4-fluorophenyl)-3-sulfydryl-1,2,4-triazole 1.95g (0.01 mol) and 4 '-[2-(piperidino) oxyethyl group]-3-brom-acetophenone 3.40g (0.01mol), add 50 mL acetic acid, after back flow reaction 3h, TLC monitoring reaction completes, be cooled to room temperature, reaction solution separates out solid gradually, suction filtration, after water washing, ethyl alcohol recrystallization, obtain white crystal 2.69 grams, yield 61.70%.
1H-NMR(300MHz，DMSO)，δ(ppm)：1.48 (2H，m)，1.65 (4H，t)，2.46 (4H，t)，2.70 (2H，t)，3.60(H，d)，4.13 (2H，t)，6.41(H，t)，6.94 (2H，d，
J=8.4Hz)，7.27(2H，d，
J=8.4Hz)，7.36(2H，d，
J=8.4Hz)，7.77(2H，d，
J=8.4Hz)； ESI-MS (m/z)：436.1 (M+H)
+。
Embodiment 8
The preparation of 2-(4-chloro-phenyl-)-7-(4 chloro-phenyl-)-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L6)
By 5-(4-chloro-phenyl-)-3-sulfydryl-1,2,4-triazole 2.11g (0.01 mol) and 4 '-chloro-3-brom-acetophenone 2.47g (0.01mol), add 50 mL acetic acid, after back flow reaction 3h, TLC monitoring reaction completes, be cooled to room temperature, reaction solution separates out solid gradually, suction filtration, after water washing, ethyl alcohol recrystallization, obtain white crystal 2.45 grams, yield 68.06%.
1H-NMR(300MHz，DMSO)，δ(ppm)：3.60(H，d)，6.42(H，t)，7.32 (2H，d，
J=8.4Hz)，7.44(2H，d，
J=8.4Hz)，7.56(2H，d，
J=8.4Hz)，8.12(2H，d，
J=8.4Hz)； ESI-MS (m/z)：360.3 (M+H)
+。
Embodiment 9
The preparation of 2-(4-chloro-phenyl-)-7-(4-fluorophenyl)-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L7)
By 5-(4-chloro-phenyl-)-3-sulfydryl-1,2,4-triazole 2.11g (0.01 mol) and 4 '-fluoro-3-brom-acetophenone 2.31g (0.01mol), add 50 mL acetic acid, after back flow reaction 3h, TLC monitoring reaction completes, be cooled to room temperature, reaction solution separates out solid gradually, suction filtration, after water washing, ethyl alcohol recrystallization, obtain white crystal 2.27 grams, yield 65.99%.
1H-NMR(300MHz，DMSO)，δ(ppm)：3.60(H，d)，6.41(H，t)，7.20 (2H，d，
J=8.4Hz)，7.36(2H，d，
J=8.4Hz)，7.56(2H，d，
J=8.4Hz)，8.14(2H，d，
J=8.4Hz)； ESI-MS (m/z)：344.2 (M+H)
+。
Embodiment 10
The preparation of 2-(4-chloro-phenyl-)-7-(4-p-methoxy-phenyl)-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L8)
By 5-(4-chloro-phenyl-)-3-sulfydryl-1,2,4-triazole 2.11g (0.01 mol) and 4 '-methoxyl group-3-brom-acetophenone 2.43g (0.01mol), add 50 mL acetic acid, after back flow reaction 3h, TLC monitoring reaction completes, be cooled to room temperature, reaction solution separates out solid gradually, suction filtration, after water washing, ethyl alcohol recrystallization, obtain white crystal 2.17 grams, yield 60.95%.
1H-NMR(300MHz，DMSO)，δ(ppm)：3.60(H，d)，3.83(3H，s)，6.41(H，t)，6.74 (2H，d，
J=8.4Hz)，7.27(2H，d，
J=8.4Hz)，7.55(2H，d，
J=8.4Hz)，8.12(2H，d，
J=8.4Hz)；ESI-MS (m/z)：356.2 (M+H)
+。
Embodiment 11
The preparation of 2-(4-chloro-phenyl-)-7-(4-hydroxy phenyl)-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L9)
By 5-(4-chloro-phenyl-)-3-sulfydryl-1,2,4-triazole 2.11g (0.01 mol) and 4 '-hydroxyl-3-brom-acetophenone 2.29g (0.01mol), add 50 mL acetic acid, after back flow reaction 3h, TLC monitoring reaction completes, be cooled to room temperature, reaction solution separates out solid gradually, suction filtration, after water washing, ethyl alcohol recrystallization, obtain white crystal 2.54 grams, yield 74.27%.
1H-NMR(300MHz，DMSO)，δ(ppm)：3.60(H，d)，6.41(H，t)，6.85 (2H，d，
J=8.4Hz)，7.26(2H，d，
J=8.4Hz)，7.56(2H，d，
J=8.4Hz)，8.13(2H，d，
J=8.4Hz)，8.61(H，s)； ESI-MS (m/z)：342.3 (M+H)
+。
Embodiment 12
2-(4-chloro-phenyl-)-7-{4-[2-(piperidino) oxyethyl group] phenyl } preparation of-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L10)
By 5-(4-chloro-phenyl-)-3-sulfydryl-1,2,4-triazole 2.11g (0.01 mol) and 4 '-[2-(piperidino) oxyethyl group]-3-brom-acetophenone 3.40g (0.01mol), add 50 mL acetic acid, after back flow reaction 3h, TLC monitoring reaction completes, be cooled to room temperature, reaction solution separates out solid gradually, suction filtration, after water washing, ethyl alcohol recrystallization, obtain white crystal 2.87 grams, yield 63.36%.
1H-NMR(300MHz，DMSO)，δ(ppm)：1.48 (2H，m)，1.64 (4H，t)，2.45 (4H，t)，2.70 (2H，t)，3.62(H，d)，4.12 (2H，t)，6.41(H，t)，6.92 (2H，d，
J=8.4Hz)，7.28(2H，d，
J=8.4Hz)，7.56(2H，d，
J=8.4Hz)，8.10(2H，d，
J=8.4Hz)； ESI-MS (m/z)：453.1 (M+H)
+。
Embodiment 13
The active determination test of acetylcholinesterase depressant
1. the preparation of material: positive control drug is set as Hydrogen bromide prostigmin(e) (SigmaN-2001), is formulated as 0.1M solution; Acetylcholinesterase (people source) (SigmaC-1682) 0.5 unit; Buffered soln is 100mM PBS solution (pH7.4), 10mM bis-sulphur dinitrobenzoic acid DTNB(D-8130) (with 100mM PBS preparation) ,-20 DEG C keep in Dark Place, now-making-now-using; 12.5mM acetylthiocholine ATCh(A-5751) be dissolved in the water ,-20 DEG C keep in Dark Place, now-making-now-using; Test medicine DMSO is prepared into 10 μMs of solution after dissolving.
2. method:
(1) by following table method processing sample;
(2) 37 DEG C of continuously jolting preheatings 15 minutes gently;
(3) 50mL ATCh and 50mL DTNB is added;
(4) 37 DEG C of continuously joltings about 20 minutes gently, until reaction solution occurs yellow;
(5) the OD value at its 412nm place is measured;
(6) calculate inhibiting rate, acetylcholine ester enzyme inhibition rate=1-(the blank group of OD experimental group-OD)/(the blank group of OD experiment contrast group-OD) × 100%, sample segment inhibiting rate is as shown in table 1;
(7) IC of acetylcholine esterase inhibition inhibit activities is recorded
50, result is as shown in table 2.
3. result:
Compound L 1, L2, L3, L4, L5, L6, L7, L8, L9 and L10 all have good inhibit activities to acetylcholinesterase.
Claims (7)
1. an acetylcholinesterase depressant, there is the effect strengthening dull-witted and Alzheimer's disease memory in patients, it is characterized in that: this compound is the 5H-[1 with general formula I, 2,4] triazole also [5,1-b] [1,3] thiazide derivative or the acceptable hydrate of its pharmacy, salt, comprise its steric isomer or tautomer;
Wherein, the R in formula I
1, R
2independently be hydrogen, methyl, halogen, hydroxyl, methoxyl group, ethanoyl, propionyl, nitro or alkoxyl group.
2. compound according to claim 1, is characterized in that: described R
1for fluorine.
3. compound according to claim 1, is characterized in that: described R
2for chlorine.
4. compound according to claim 1, is characterized in that: described R
2for 2-(piperidino) oxyethyl group.
5. compound according to claim 1, comprising:
2-(4-fluorophenyl)-7-(4 chloro-phenyl-)-5H-[1,2,4] triazole is [5,1-b] [1,3] thiazine (L1) also; 2-(4-fluorophenyl)-7-(4-fluorophenyl)-5H-[1,2,4] triazole is [5,1-b] [1,3] thiazine (L2) also;
2-(4-fluorophenyl)-7-(4-p-methoxy-phenyl)-5H-[1,2,4] triazole is [5,1-b] [1,3] thiazine (L3) also;
2-(4-fluorophenyl)-7-(4-hydroxy phenyl)-5H-[1,2,4] triazole is [5,1-b] [1,3] thiazine (L4) also;
2-(4-fluorophenyl)-7-{4-[2-(piperidino) oxyethyl group] phenyl }-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L5);
2-(4-chloro-phenyl-)-7-(4 chloro-phenyl-)-5H-[1,2,4] triazole is [5,1-b] [1,3] thiazine (L6) also;
2-(4-chloro-phenyl-)-7-(4-fluorophenyl)-5H-[1,2,4] triazole is [5,1-b] [1,3] thiazine (L7) also;
2-(4-chloro-phenyl-)-7-(4-p-methoxy-phenyl)-5H-[1,2,4] triazole is [5,1-b] [1,3] thiazine (L8) also;
2-(4-chloro-phenyl-)-7-(4-hydroxy phenyl)-5H-[1,2,4] triazole is [5,1-b] [1,3] thiazine (L9) also;
2-(4-chloro-phenyl-)-7-{4-[2-(piperidino) oxyethyl group] phenyl }-5H-[1,2,4] triazole also [5,1-b] [1,3] thiazine (L10).
6. the preparation method of compound according to claim 1, is characterized in that: its synthetic route is shown below.
7. compound according to claim 1 is for the preparation of the purposes for the treatment of senile dementia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510286939.3A CN104926838B (en) | 2015-05-31 | 2015-05-31 | 5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510286939.3A CN104926838B (en) | 2015-05-31 | 2015-05-31 | 5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104926838A true CN104926838A (en) | 2015-09-23 |
| CN104926838B CN104926838B (en) | 2017-04-12 |
Family
ID=54114284
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510286939.3A Expired - Fee Related CN104926838B (en) | 2015-05-31 | 2015-05-31 | 5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104926838B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115197244A (en) * | 2022-09-03 | 2022-10-18 | 石家庄学院 | [1,2,4] triazino [3,2-b ] [1,3,5] thiadiazine derivative and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101220043A (en) * | 2008-01-24 | 2008-07-16 | 沈阳药科大学 | Benzothiazolo [3, 2,-a]-miazine derivant and uses thereof |
| CN101503414A (en) * | 2009-03-04 | 2009-08-12 | 沈阳药科大学 | Thiazolo[3,2-b]-1,2,4-triazine derivative and use thereof |
| CN102807575A (en) * | 2012-08-09 | 2012-12-05 | 石家庄学院 | 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative and application thereof |
| CN103012439A (en) * | 2012-11-15 | 2013-04-03 | 沈阳药科大学 | Benzoyl substituted thiazolo[3,2-b]-1,2,4-triazine derivative and application thereof |
| CN103012438A (en) * | 2012-11-15 | 2013-04-03 | 沈阳药科大学 | Alkoxy substituted thiazolo [3,2-b]-1,2,4-triazine derivatives and application thereof |
-
2015
- 2015-05-31 CN CN201510286939.3A patent/CN104926838B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101220043A (en) * | 2008-01-24 | 2008-07-16 | 沈阳药科大学 | Benzothiazolo [3, 2,-a]-miazine derivant and uses thereof |
| CN101503414A (en) * | 2009-03-04 | 2009-08-12 | 沈阳药科大学 | Thiazolo[3,2-b]-1,2,4-triazine derivative and use thereof |
| CN102807575A (en) * | 2012-08-09 | 2012-12-05 | 石家庄学院 | 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative and application thereof |
| CN103012439A (en) * | 2012-11-15 | 2013-04-03 | 沈阳药科大学 | Benzoyl substituted thiazolo[3,2-b]-1,2,4-triazine derivative and application thereof |
| CN103012438A (en) * | 2012-11-15 | 2013-04-03 | 沈阳药科大学 | Alkoxy substituted thiazolo [3,2-b]-1,2,4-triazine derivatives and application thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115197244A (en) * | 2022-09-03 | 2022-10-18 | 石家庄学院 | [1,2,4] triazino [3,2-b ] [1,3,5] thiadiazine derivative and application thereof |
| CN115197244B (en) * | 2022-09-03 | 2023-07-07 | 石家庄学院 | [1,2,4] triazino [3,2-b ] [1,3,5] thiadiazine derivatives and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104926838B (en) | 2017-04-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO20061406L (en) | Organic compounds | |
| US8487095B2 (en) | Acid addition salts, hydrates and polymorphs of 5-(2,4-dihydroxy-5-iso-propyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide and formulations comprising these forms | |
| CN102807575B (en) | 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative and application thereof | |
| US7381739B2 (en) | 2,4-substituted indoles and methods of use | |
| EP1981878A1 (en) | Indazole heteroaryl derivatives | |
| JP2005538111A5 (en) | ||
| PE20081160A1 (en) | ARILSULFONIL-PYRROLIDINES AS 5-HT6 INHIBITORS | |
| HUT70414A (en) | Geneserine derivatives as cholinesterase inhibitors and pharmaceutical compositions containing them | |
| JP2010536713A5 (en) | ||
| CN104926838A (en) | 5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative and application | |
| CN104788473A (en) | Antibacterial compound as well as preparation method and application thereof | |
| CN104945415A (en) | 7H-benzo-isoxazole-[7,6-e][1,3]oxazine derivatives and application | |
| CN105873439A (en) | Alkyl linked quinolinyl modulators of RORyt | |
| CN104892640A (en) | 2-phenyl-6-benzoyl-thiazolo[3,2-b][1,2,4]-triazole derivative and application thereof | |
| CN102796121B (en) | 3-aryl-7H-thiazol[3,2-b]-1,2,4-triazinyl-7-one derivatives and application thereof | |
| CN104844628A (en) | 2H,6H-pyrimido[2,1-b][1,3]thiazine derivative and application thereof | |
| CN107383068B (en) | Thiazole and triazole -6- acetamide derivative and application | |
| WO2003000681A1 (en) | Antibacterial having quinolinecarboxamide skeleton | |
| NO20080498L (en) | Fluorine-substituted 2-oxo-azepane derivatives | |
| CN103044460B (en) | 3,5,7-triphenyl-5H-thiazolo[3,2-a]pyrimidin derivatives and application thereof | |
| CN112047962B (en) | 2H-thiazolo [3,2-b ] -1,2, 4-triazine-3, 7-diketone derivative and application thereof | |
| DE60113689T2 (en) | 2-AMINOTHIAZOLINE DERIVATIVES AND THEIR USE AS NO-SYNTHASE INHIBITORS | |
| ATE307811T1 (en) | TRIAZOLES FOR THE TREATMENT OF DISEASES RESPONSIVE TO MODULATION OF THE DOPAMINE D3 RECEPTOR | |
| EP2300434A1 (en) | Dihydropyrazole derivatives as tyrosine kinase modulators for the treatment of tumors | |
| CN103012439B (en) | Benzoyl substituted thiazolo[3,2-b]-1,2,4-triazine derivative 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 | ||
| CB03 | Change of inventor or designer information |
Inventor after: Liu Sijie Inventor after: Zhou Ran Inventor after: Xiao Xiao Inventor after: Lei Ni Inventor after: Shi Lanxiang Inventor after: Guo Ruixia Inventor before: Liu Sijie Inventor before: Zhang Baohua Inventor before: Lei Ni Inventor before: He Jingyu Inventor before: Shi Lanxiang Inventor before: Guo Ruixia |
|
| COR | Change of bibliographic data | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170412 Termination date: 20180531 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |