CN102807575A - 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative and application thereof - Google Patents

3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative and application thereof Download PDF

Info

Publication number
CN102807575A
CN102807575A CN2012102811064A CN201210281106A CN102807575A CN 102807575 A CN102807575 A CN 102807575A CN 2012102811064 A CN2012102811064 A CN 2012102811064A CN 201210281106 A CN201210281106 A CN 201210281106A CN 102807575 A CN102807575 A CN 102807575A
Authority
CN
China
Prior art keywords
thienyl
alkyl
aryl
alkoxy
independently
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
Application number
CN2012102811064A
Other languages
Chinese (zh)
Other versions
CN102807575B (en
Inventor
刘斯婕
何敬宇
史兰香
张宝华
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shijiazhuang University
Original Assignee
Shijiazhuang University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Shijiazhuang University filed Critical Shijiazhuang University
Priority to CN201210281106.4A priority Critical patent/CN102807575B/en
Publication of CN102807575A publication Critical patent/CN102807575A/en
Application granted granted Critical
Publication of CN102807575B publication Critical patent/CN102807575B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Landscapes

  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention discloses 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative or pharmaceutically acceptable hydrate, and salt therof, including stereomer or tautomer, wherein R1 is independently selected from C1-C6 alkyl and C1-C6 alkoxy; R2 is independently selected from C1-C6 alkyl and C1-C6 alkoxy; R3 can be selected from C1-C10 amino-alkoxy freely selectively substituted by one or two substituent groups independently selected from C1-C6 alkyl, C1-C6 alkoxy, substituted or un-substituted formamyl alkoxy, and hydroxyl and halogen substituent group, and R4 is independently selected from hydrogen, C1-C6 alkyl, ethanoyl and halogen. The 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative based on the invention has an obvious inbibitional effect on acetylcholinesterase. Therefore, the 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative is used for enhancing memory of patients suffering from dementia and alzheimer's disease.

Description

3-aryl-5-thienyl-5H-thiazole is [3,2-a] pyridine derivatives and application thereof also
Technical field
The invention belongs to medical technical field, relate to 3-aryl-5-thienyl-5 H-thiazole also [3,2-a] pyridine derivatives and preparation method thereof with as acetylcholinesterase depressant, be used to improve and suffer from the dull-witted application of remembering with the Alzheimer's patient.
Background technology
The degeneration of the cholinergic neuron [it plays an important role in recognition function (comprising memory)] in Alzheimer's and the basal forebrain is relevant.Because the result of said degeneration, the patient who suffers from this disease is synthetic at vagusstoff, show tangible decay aspect choline acetyltransferase activity, acetylcholine esterase active and the choline absorption.
Therefore known acetylcholinesterase depressant can be used for improving person with Alzheimer's disease's memory being effectively aspect the raising cholinergic activity.Through acetylcholine esterase inhibition, said compound can improve the level of neurotransmission mediator vagusstoff in the brain, but so hypermnesis.
Existing acetylcholinesterase depressant such as tacrine, this bright, lycoremines etc. still exist resistance or pharmacokinetics defective.Compound according to the invention has the structure type novelty as the acetylcholinesterase depressant of brand new type, and drug action and existing medicine quite or be superior to the characteristics of existing medicine have excellent application value and development prospect.
Summary of the invention
The object of the present invention is to provide a kind of 3-aryl-5-thienyl-5 H-thiazole is [3,2-a] pyridine derivatives also, and it has good inhibiting activity of acetylcholinesterase.
Another object of the present invention is to provide above-mentioned 3-aryl-5-thienyl-5 H-thiazole is the preparation method of [3,2-a] pyridine derivatives also.
A purpose more of the present invention is to provide above-mentioned 3-aryl-5-thienyl-5 H-thiazole is the purposes of [3,2-a] pyridine derivatives also.
Below describe the present invention.
The present invention provides the 3-aryl-5-thienyl-5 of following general formula I H-thiazole is [3,2-a] pyridine derivatives or its pharmacologically acceptable salts also.Structure is seen Fig. 1:
Wherein, R 1Independently be selected from C 1-C 6Alkyl and C 1-C 6Alkoxyl group; R 2Independently be selected from C 1-C 6Alkyl and C 1-C 6Alkoxyl group; R 3Can select arbitrarily independently to be selected from C by 1 or 2 1-C 6Alkyl, C 1-C 6Alkoxyl group, C 1-C 10Select the substituting group of substituted aminoalkoxy, replacement or non-substituted-amino formyl radical alkoxyl group, hydroxyl and halogen to replace arbitrarily; R 4Independently be selected from hydrogen, C 1-C 6Alkyl, ethanoyl and halogen.
" pharmacy acceptable salt " referred to keep the biopotency and the character of formula I compound, and the conventional acid additive salt or the base addition salt that form with suitable non-toxicity organic or inorganic acid or organic or inorganic alkali.The instance 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, PHENRAMINE MALEATE, mesylate, 2-naphthalenesulfonate, nicotinate; Nitrate salt, oxalate, pamoate, YM 115H salt, persulphate, 3-phenylpropionic acid salt, picrate; Pivalate, propionic salt, SUMATRIPTAN SUCCINATE, vitriol, tartrate, thiocyanate-, tosylate and undecylate.Alkali salt comprises ammonium salt, an alkali metal salt, for example sodium and sylvite, alkaline earth salt, for example calcium and magnesium salts; The salt of organic bases, dicyclohexyl amine salt for example, N-methyl-D-glucamine salt and amino acid whose salt, for example l-arginine; Methionin etc., and alkaline nitrogen-containing group can use such reagent quaternized, for example elementary alkyl halide; Like methyl, ethyl, the chlorine of propyl group and butyl, bromine and iodide; The sulfuric acid dialkyl, like methyl-sulfate, diethyl ester, dibutylester and diamyl ester; Long-chain halogenide, like decyl, lauryl, the chlorine of myristyl and stearyl-, bromine and iodide; Aralkyl halide is like bromide of benzyl and styroyl etc.The acid that is preferred for generating acid salt comprises hydrochloric acid and acetic acid.
" pharmaceutically acceptable " like pharmaceutically acceptable ground carrier, excipient, prodrug etc., refers on the pharmacology acceptable and the patient of administration particular compound had basically no toxicity.
The present invention also provides the preparation method of above-mentioned compound of Formula I, and this method is seen Fig. 2.
The invention still further relates to the method that suppresses E.C. 3.1.1.7 in the Mammals, this method comprises formula I compound or its steric isomer or its acid salt that pharmaceutically is suitable for of taking the acetylcholine esterase inhibition effective dose to Mammals.
The present invention also relates to the method for formula I hypermnesis or treatment or prevention Alzheimer's, this method comprises formula I compound or its steric isomer or its acid salt that pharmaceutically is suitable for of taking hypermnesis or treatment or prevention Alzheimer's effective dose.
Description of drawings
Fig. 1 is 3-aryl-5-thienyl-5 H-thiazole is the general structure figure of [3,2-a] pyridine derivatives also;
Fig. 2 is 3-aryl-5-thienyl-5 H-thiazole is the synthetic route chart of [3,2-a] pyridine derivatives also;
Fig. 3 is the treatment process figure of sample in the inhibiting activity of acetylcholinesterase, determination test;
Fig. 4 is the figure as a result of sample segment E.C. 3.1.1.7 inhibiting rate.
Further illustrate the present invention through following examples, but should notice that scope of the present invention does not receive any restriction of these embodiment.
Specific embodiment
Embodiment 1
The preparation of 6-methyl-5-ethanoyl-4-thienyl-2-sulfo-pyrimidine
In the round-bottomed flask of 250 ml, add 2 of thiophenecarboxaldehyde 0.1 mol, thiocarbamide 0.1 mol, methyl ethyl diketone 0.11 mol, ethanol 30 ml, concentrated hydrochloric acid, stir 60 ℃ of reaction 10 h.Cooling, suction filtration, filter cake absolute ethyl alcohol recrystallization obtains yellow crystals 20.4 grams, yield 80.9%.MS?m/z?(M)?252。
Embodiment 2
The preparation of 6-methyl-4-thienyl-2-sulfo-pyrimidine-5-carboxylic acid ethyl ester
In the round-bottomed flask of 250 ml, add 2 of thiophenecarboxaldehyde 0.1 mol, thiocarbamide 0.1 mol, methyl ethyl diketone 0.11 mol, ethanol 30 ml, concentrated hydrochloric acid, stir 60 ℃ of reaction 10 h.Cooling, suction filtration, filter cake absolute ethyl alcohol recrystallization obtains yellow crystals 24.6 grams, yield 87.2%.MS?m/z?(M)?282。
Embodiment 3
7-methyl-5-thienyl-3-(4-hydroxy phenyl)-5 H-thiazole is the preparation of [3,2-a] pyrimidine-6-carboxylic acid, ethyl ester also
With 6-methyl-4-thienyl-2-sulfo-pyrimidine-5-carboxylic acid ethyl ester 2.82 g (10 mmol), 4-hydroxyl chloroacetophenone 1.71 g (10 mmol), sodium-acetate/Glacial acetic acid min. 99.5 (2 g/20 mL), heating reflux reaction 8-24 hour, TLC monitoring reaction.After the cooling, suction filtration, the absolute ethyl alcohol recrystallization gets 2.07 g white powders, yield 54 %.MS:?396； 1H-NMR(300MHz,?DMSO)δ(ppm):?1.14(3H,?t),?2.49(3H,?s),?4.11(2H,?q),?5.61(1H,?d),?6.29(1H,?s),?6.41(1H,?d)?6.93(2H,?d,? J=8.4Hz),?7.28(2H,?d,? J=8.4Hz),?7.31(1H,?d),?7.84(1H,?d),?10.17(1H,?s)。
Embodiment 4
7-methyl-5-thienyl-3-(4-chloro-phenyl-)-5 H-thiazole is the preparation of [3,2-a] pyrimidine-6-carboxylic acid, ethyl ester also
With 6-methyl-4-thienyl-2-sulfo-pyrimidine-5-carboxylic acid ethyl ester 2.82 g (10 mmol), 4-chlorine chloroacetophenone 1.89 g (10 mmol), sodium-acetate/Glacial acetic acid min. 99.5 (2 g/20 mL), heating reflux reaction 8-24 hour, TLC monitoring reaction.After the cooling, suction filtration, the absolute ethyl alcohol recrystallization gets 2.19 g white powders, yield 52.9 %.MS:?414； 1H-NMR(300MHz,?DMSO)δ(ppm):?1.14(3H,?t),?2.49(3H,?s),?4.11(2H,?q),?5.61(1H,?d),?6.29(1H,?s),?6.41(1H,?d),?7.31(1H,?d),?7.64(2H,?d,? J=8.7Hz),?7.68(2H,?d,? J=8.7Hz)，7.84(1H,?d)。
Embodiment 5
7-methyl-5-thienyl-3-(4-aminomethyl phenyl)-5 H-thiazole is the preparation of [3,2-a] pyrimidine-6-carboxylic acid, ethyl ester also
With 6-methyl-4-thienyl-2-sulfo-pyrimidine-5-carboxylic acid ethyl ester 2.82 g (10 mmol), 4-methyl chloroacetophenone 1.78 g (10 mmol), sodium-acetate/Glacial acetic acid min. 99.5 (2 g/20 mL), heating reflux reaction 8-24 hour, TLC monitoring reaction.After the cooling, suction filtration, the absolute ethyl alcohol recrystallization gets 2.32 g white powders, yield 58.9 %.MS:?394； 1H-NMR(300MHz,?DMSO)δ(ppm):?1.14(3H,?t),?2.49(3H,?s),?4.11(2H,?q),?5.61(1H,?d),?6.29(1H,?s),?6.41(1H,?d),?6.73(2H,?d,? J=8.7)，7.15(2H,?d,? J=8.7)，7.31(1H,?d),?7.84(1H,?d)。
Embodiment 6
7-methyl-3-[4-(2-dimethylamino) ethoxyl phenenyl]-5-thienyl-5 H-thiazole is the preparation of [3,2-a] pyrimidine-6-carboxylic acid, ethyl ester also
With 7-methyl-5-thienyl-3-(4-hydroxy phenyl)-5 H-thiazole is [3,2-a] pyrimidine-6-carboxylic acid, ethyl ester 0.39 g (1 mmol) also, and 2-chloroethyl dimethylamino hydrochloride 0.14 g (1 mmol) is dissolved in the absolute ethyl alcohol earlier; Add potassiumiodide 0.22 g again, salt of wormwood 2.76 g, reflux 8 h; Behind the stopped reaction, be cooled to room temperature.Suction filtration is removed potassiumiodide and salt of wormwood, solvent is revolved to steam remove, and gets red solid, and the absolute ethyl alcohol recrystallization gets white needle-like crystals 0.31 g, yield 72.8 %.MS:467。 1H-NMR(300MHz,?DMSO)δ(ppm):?1.14(3H,?t),?2.23(6H,?s)，2.49(3H,?s),?2.65(2H,?m)，3.96(2H,?q)，4.11(2H,?q),?5.61(1H,?d),?6.29(1H,?s),?6.41(1H,?d)，6.93(2H,?d,? J=8.4Hz),?7.28(2H,?d,? J=8.4Hz),?7.31(1H,?d),?7.84(1H,?d)。
Embodiment 7
6-ethanoyl-7-methyl-3-(4-hydroxy phenyl)-5-thienyl-5 H-thiazole is the preparation of [3,2-a] pyrimidine also
With 6-methyl-5-ethanoyl-4-thienyl-2-sulfo-pyrimidine 2.52 g (10 mmol), 4-hydroxyl chloroacetophenone 1.89 g (10 mmol), sodium-acetate/Glacial acetic acid min. 99.5 (2 g/20 mL), heating reflux reaction 8-24 hour, TLC monitoring reaction.After the cooling, suction filtration, the absolute ethyl alcohol recrystallization gets 2.57 g white powders, yield 70.2 %.MS:?366； 1H-NMR(300MHz,?DMSO)δ(ppm):?2.22(3H,?t),?2.48(3H,?s),?5.61(1H,?d),?6.29(1H,?s),?6.41(1H,?d),?6.73(2H,?d,? J=8.7)，7.15(2H,?d,? J=8.7)，7.31(1H,?d),?7.84(1H,?d)，10.15(1H,?s)。
Embodiment 8
6-ethanoyl-7-methyl-3-(4-chloro-phenyl-)-5-thienyl-5 H-thiazole is the preparation of [3,2-a] pyrimidine also
With 6-methyl-5-ethanoyl-4-thienyl-2-sulfo-pyrimidine 2.52 g (10 mmol), 4-chlorine chloroacetophenone 1.89 g (10 mmol), sodium-acetate/Glacial acetic acid min. 99.5 (2 g/20 mL), heating reflux reaction 8-24 hour, TLC monitoring reaction.After the cooling, suction filtration, the absolute ethyl alcohol recrystallization gets 2.57 g white powders, yield 70.2 %.MS:?384； 1H-NMR(300MHz,?DMSO)δ(ppm):?2.22(3H,?s),?2.49(3H,?s),?5.61(1H,?d),?6.29(1H,?s),?6.41(1H,?d),?7.31(1H,?d),?7.64(2H,?d,? J=8.7Hz),?7.68(2H,?d,? J=8.7Hz)，7.84(1H,?d)。
Embodiment 9
6-ethanoyl-7-methyl-3-(4-aminomethyl phenyl)-5-thienyl-5 H-thiazole is the preparation of [3,2-a] pyrimidine also
With 6-methyl-5-ethanoyl-4-thienyl-2-sulfo-pyrimidine 2.52 g (10 mmol), 4-methyl chloroacetophenone 1.78 g (10 mmol), sodium-acetate/Glacial acetic acid min. 99.5 (2 g/20 mL), heating reflux reaction 8-24 hour, TLC monitoring reaction.After the cooling, suction filtration, the absolute ethyl alcohol recrystallization gets 2.43 g white powders, yield 66.7%.MS:?364； 1H-NMR(300MHz,?DMSO)δ(ppm):?2.22(3H,?s),?2.49(3H,?s),?5.61(1H,?d),?6.29(1H,?s),?6.41(1H,?d),?6.73(2H,?d,? J=8.7)，7.15(2H,?d,? J=8.7)，7.31(1H,?d),?7.84(1H,?d)。
Embodiment 10
6-ethanoyl-7-methyl-3-[4-(2-dimethylamino) ethoxyl phenenyl]-5-thienyl-5 H-thiazole is the preparation of [3,2-a] pyrimidine also
6-ethanoyl-7-methyl-3-(4-hydroxy phenyl)-5-thienyl-5 H-thiazole is [3,2-a] pyrimidine 0.36 g (1 mmol) also, and 2-chloroethyl dimethylamino hydrochloride 0.14 g (1 mmol) is dissolved in earlier in the absolute ethyl alcohol, adds potassiumiodide 0.22 g again, salt of wormwood 2.76 g, and reflux 8 h behind the stopped reaction, are cooled to room temperature.Suction filtration is removed potassiumiodide and salt of wormwood, solvent is revolved to steam remove, and gets red solid, and the absolute ethyl alcohol recrystallization gets white needle-like crystals 0.38 g, yield 86.9 %.MS:437。 1H-NMR(300MHz,?DMSO)δ(ppm):?2.22(3H,?s),?2.23(6H,?s)，2.49(3H,?s),?2.65(2H,?m)，4.11(2H,?q),?5.61(1H,?d),?6.29(1H,?s),?6.41(1H,?d)，6.93(2H,?d,? J=8.4Hz),?7.28(2H,?d,? J=8.4Hz),?7.31(1H,?d),?7.84(1H,?d)。
Embodiment 11
The active determination test of acetylcholinesterase depressant
Materials and methods:
Supply the preparation of test agent: positive control drug is set at Hydrogen bromide prostigmin(e) (SigmaN-2001), is formulated as 0.1M solution;
E.C. 3.1.1.7 (people source) is 0.5 unit (SigmaC-1682);
Buffered soln is 100mM PBS solution (pH7.4), 10mM two sulphur dinitrobenzoic acid DTNB (D-8130) (with 100mM PBS preparation), and-20 ℃ keep in Dark Place now-making-now-using;
12.5mM acetylthiocholine ATCh (A-5751) is dissolved in the water ,-20 ℃ keep in Dark Place now-making-now-using;
Be prepared into 10 μ M solution after receiving the reagent thing with the DMSO dissolving.
Method and result:
1. handle the sample (see figure 3) as follows;
2. 37 ℃ of jolting preheatings 15 minutes gently continuously;
3. add 50mL ATCh and 50mL DTNB;
4. 37 ℃ of about 20 minutes of joltings gently continuously occur yellow up to reaction solution;
5. measure the OD value at its 412nm place;
6. calculating inhibiting rate, the sample segment inhibiting rate (see figure 4) that is shown in the following figure.

Claims (7)

1. the aryl alkanoic acid of general formula I and astaz n or the acceptable hydrate of its pharmacy, salt comprise its steric isomer or tautomer, it is characterized in that it has following general formula (I):
Wherein, R 1Independently be selected from C 1-C 6Alkyl and C 1-C 6Alkoxyl group;
R 2Independently be selected from C 1-C 6Alkyl and C 1-C 6Alkoxyl group;
R 3Can select arbitrarily independently to be selected from C by 1 or 2 1-C 6Alkyl, C 1-C 6Alkoxyl group, C 1-C 10Select the substituting group of substituted aminoalkoxy, replacement or non-substituted-amino formyl radical alkoxyl group, hydroxyl and halogen to replace arbitrarily;
R 4Independently be selected from hydrogen, C 1-C 6Alkyl, ethanoyl and halogen.
2. a pharmaceutical composition comprises as any one compound and medicine acceptable carrier or excipient in the claim 1 of activeconstituents.
3. according to said this analog derivative of claim 1, it is characterized in that: R 1Preferable methyl.
4. according to said this analog derivative of claim 1, it is characterized in that: R 2Preferable methyl.
5. according to said this analog derivative of claim 1, it is characterized in that: R wherein 3Preferred 4-[2-(1-piperidines) oxyethyl group].
6. according to said this analog derivative of claim 1, it is characterized in that: R wherein 4Preferred hydrogen.
7. any one compound and compsn thereof the application in preparation treatment degenerative dementia disease drug in the claim 1.
CN201210281106.4A 2012-08-09 2012-08-09 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative and application thereof Expired - Fee Related CN102807575B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201210281106.4A CN102807575B (en) 2012-08-09 2012-08-09 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201210281106.4A CN102807575B (en) 2012-08-09 2012-08-09 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative and application thereof

Publications (2)

Publication Number Publication Date
CN102807575A true CN102807575A (en) 2012-12-05
CN102807575B CN102807575B (en) 2015-03-25

Family

ID=47231461

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201210281106.4A Expired - Fee Related CN102807575B (en) 2012-08-09 2012-08-09 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative and application thereof

Country Status (1)

Country Link
CN (1) CN102807575B (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103044460A (en) * 2013-01-30 2013-04-17 石家庄学院 3,5,7-triphenyl-5H-thiazolo[3,2-a]pyrimidin derivatives and application thereof
CN104844628A (en) * 2015-04-16 2015-08-19 石家庄学院 2H,6H-pyrimido[2,1-b][1,3]thiazine derivative and application thereof
CN104892640A (en) * 2015-05-28 2015-09-09 石家庄学院 2-phenyl-6-benzoyl-thiazolo[3,2-b][1,2,4]-triazole derivative and application thereof
CN104926838A (en) * 2015-05-31 2015-09-23 石家庄学院 5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative and application
CN104945415A (en) * 2015-06-17 2015-09-30 石家庄学院 7H-benzo-isoxazole-[7,6-e][1,3]oxazine derivatives and application

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
陈兰妹: "噻唑并[3,2-a]嘧啶类化合物的设计、合成及生物活性研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103044460A (en) * 2013-01-30 2013-04-17 石家庄学院 3,5,7-triphenyl-5H-thiazolo[3,2-a]pyrimidin derivatives and application thereof
CN104844628A (en) * 2015-04-16 2015-08-19 石家庄学院 2H,6H-pyrimido[2,1-b][1,3]thiazine derivative and application thereof
CN104892640A (en) * 2015-05-28 2015-09-09 石家庄学院 2-phenyl-6-benzoyl-thiazolo[3,2-b][1,2,4]-triazole derivative and application thereof
CN104926838A (en) * 2015-05-31 2015-09-23 石家庄学院 5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative and application
CN104926838B (en) * 2015-05-31 2017-04-12 石家庄学院 5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative and application
CN104945415A (en) * 2015-06-17 2015-09-30 石家庄学院 7H-benzo-isoxazole-[7,6-e][1,3]oxazine derivatives and application

Also Published As

Publication number Publication date
CN102807575B (en) 2015-03-25

Similar Documents

Publication Publication Date Title
US6552048B2 (en) Sulfonylcarboxamide derivatives, process for their preparation and their use as pharmaceuticals
DE69839338T2 (en) PYRIDO (2,3-D) PYRIMIDINE AND 4-AMINO-PYRIMIDINE AS INHIBITORS OF CELLULAR PROLIFERATION
AU2018241154A1 (en) Toxic Aldehyde Related Diseases and Treatment
CN102858177B (en) Catechol-O-methyltransferase inhibitor and the purposes in treatment mental disorder thereof
CN102807575A (en) 3-aryl-5-thienyl-5H-thiazolo [3,2-a] pyrimidine derivative and application thereof
US8569308B2 (en) Substituted heteroarylamine carboxamide analogs as mGluR5 negative allosteric modulators and methods of making and using the same
EP2151435A1 (en) Pharmaceutical composition for treatment of alzheimer's disease
US11845728B2 (en) Compounds and methods for treating cancer
JP2014528428A (en) Monoacylglycerol lipase inhibitors for the treatment of metabolic disorders and related disorders
WO2007095812A1 (en) Substituted [1,3,5] triazine compounds, their processes for preparation and uses thereof
IL90309A (en) Derivatives of 6-phenyl-3-(piperazinylalkyl)-2,4(1h,3h)-pyrimidinedione their preparation and pharmaceutical compositions containing them
JPH06509318A (en) Tropolone derivatives and pharmaceutical compositions thereof for preventing and treating ischemic diseases
CN102796121B (en) 3-aryl-7H-thiazol[3,2-b]-1,2,4-triazinyl-7-one derivatives and application thereof
CN107382974B (en) Application of pyrimidinamine compound as cyclin-dependent kinase 4/6 inhibitor
WO2018196861A1 (en) Guanidine derivative
CN103044460B (en) 3,5,7-triphenyl-5H-thiazolo[3,2-a]pyrimidin derivatives and application thereof
CN104945415A (en) 7H-benzo-isoxazole-[7,6-e][1,3]oxazine derivatives and application
US9045437B2 (en) 2-aryl-4-quinazolinones and their pharmaceutical compositions
WO2019136514A1 (en) 5-(pyrimidin-4-yl)thiazol-2-yl urea derivatives as therapeutic agents
CN107383068B (en) Thiazole and triazole -6- acetamide derivative and application
US20110294772A1 (en) Use of cyclosquaramide compounds as anti-tumour agents
CN104892640A (en) 2-phenyl-6-benzoyl-thiazolo[3,2-b][1,2,4]-triazole derivative and application thereof
CN104926838A (en) 5H-[1, 2, 4] triazole [5, 1-b] [1, 3] thiazide derivative and application
EP1715921B1 (en) Tetrahydroindolone derivatives for treatment of neurological conditions
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
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20150325

Termination date: 20150809

EXPY Termination of patent right or utility model