Condensation of β-Oxoanilide 1 with active methylene derivatives 2a,bafforded the pyridine derivative 5, and with crotononitrile afforded the pyridine 8. Compounds 9 and 11a-c were obtained by reaction of 1 with malo...Condensation of β-Oxoanilide 1 with active methylene derivatives 2a,bafforded the pyridine derivative 5, and with crotononitrile afforded the pyridine 8. Compounds 9 and 11a-c were obtained by reaction of 1 with malononitrile dimer and arylidinemalononitrile 10a-10c. In contrast, when compound 1 reacted with ethoxymethylen malononitrile afforded the pyridine derivative 13. On the other hand, treatment of 1 with anthranilic acid gave the quinoline derivative 14. Also, reactions of 1 with isothiocyanate derivatives afforded compounds 16-18. The reaction of 1 with chalcone derivative afforded the pyridine derivative 22. Treatment of compound 1 with thiourea produced pyrimidine derivative 23. Furthermore, compound 1 converted into pyrimidinethione 24a and pyrimidinone 24b on treatment with a mixture of aromatic aldehydes and thiourea or urea respectively. Reaction of 24a with hydrazonyl halide, thiosemicarbazide and arylidinecyanothioacetamide afforded compounds 26, 28 and 29. Compound 29 was treated with chloroacetonitrile to afford compound 30. Six compounds from the newly synthesized were screened for antibacterial and antifungal activity against bacteria staphylococcus aureus, bacillus cereus and klebsiella pneumonia and fungi aspergillus flavus and aspergillus ochraceous, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, 1H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.展开更多
The magnetic nanoparticles supported silica sulfuric acid was used as an efficient catalyst for the synthesis of pyrimido[4,5-b]quinoIines and indeno fused pyrido（2,3-d]pyrimidines in water.The desired products were ...The magnetic nanoparticles supported silica sulfuric acid was used as an efficient catalyst for the synthesis of pyrimido[4,5-b]quinoIines and indeno fused pyrido（2,3-d]pyrimidines in water.The desired products were obtained in excellent yields.Fe_3O_4@SiO_2-SO_3H was readily recovered using an external magnet and could be reused several times without significant loss of reactivity.展开更多
Room temperature ionic liquids were used as a "green" recyclable alternative to conventional solvents in the synthesis of pharmaceutically useful compounds 2-arylimidazo[1, 2-a] pyrimidines through Tschotsch...Room temperature ionic liquids were used as a "green" recyclable alternative to conventional solvents in the synthesis of pharmaceutically useful compounds 2-arylimidazo[1, 2-a] pyrimidines through Tschotschibabin reaction of a-bromoacetophenones with 2-aminopyrimidine in good yields.展开更多
A new synthetic strategy for the synthesis of novel 3-（3-（3-methyl-4-nitroisoxazol-5-yl）-2-phenyl-1-（5,7-diaryl-7H-thia- zolo[3,2-a]pyrimidin-3-yl）propyl）-5,7-diaryl-7H-thiazolo[3,2-a]pyrimidines （7a-i） analog...A new synthetic strategy for the synthesis of novel 3-（3-（3-methyl-4-nitroisoxazol-5-yl）-2-phenyl-1-（5,7-diaryl-7H-thia- zolo[3,2-a]pyrimidin-3-yl）propyl）-5,7-diaryl-7H-thiazolo[3,2-a]pyrimidines （7a-i） analogues is described. Reaction of 3-（2- （3-methyl-4-nitroisoxazole-5-yl）-l-phenylethyl）pentane-2,4-dione （3） with two moles of thiourea in presence of iodine and CuO afforded 4-（1-（2-aminothiazol-4-yl）-3-（3-methyl-4-nitroisoxazol-5-yl）-2-aryl propylthiazol-2-amine （5）. Compound 5 on reaction with two moles of chalcone （6） furnished novel 3-（3-（3-methyl-4-nitroisoxazol-5-yl）-2-phenyl-1-（5,7-diaryl-7H-thiazolo[3,2- a]pyrimidin-3-yl）propyl）-5,7-diaryl-7H-thiazolo[3,2-a ]pyrimidines （Ta-i）.展开更多
A direct metal-free C-H amination reaction of cinnamaldehydes and amidines to realize the synthesis of polysubstituted pyrimidines was developed in the presence of base. This greener synthetic methodology provides a s...A direct metal-free C-H amination reaction of cinnamaldehydes and amidines to realize the synthesis of polysubstituted pyrimidines was developed in the presence of base. This greener synthetic methodology provides a straightforward approach to the synthesis of a variety of pyrimidine derivatives under mild reaction condition using oxygen as sole oxidants.展开更多
＂Why do arginine and pyrimidines have to be considered together？＂ This was the question I asked when I was invited by Barbara Zimmermann to attend the 23rd Intemational Conference on Arginine and Pyrimidines （ICAP...＂Why do arginine and pyrimidines have to be considered together？＂ This was the question I asked when I was invited by Barbara Zimmermann to attend the 23rd Intemational Conference on Arginine and Pyrimidines （ICAP） three years ago. The meeting was held in the summer of 2012 at Bogota, Columbia, known as the ＂the Athens of South America＂. I am not alone in wanting to know more about the relationship between arginine and pyrimidines. Last summer, when ! was organising the next ICAP meeting at Oxford （Aughey et al., 2014）, one of my colleagues asked me, ＂Why such a weird name for a conference？＂ I am not sure if I had given her a satisfying answer and I was enthused to find out what the reasons may be.展开更多
Novel pyrido[2,3-d]pyrimidine derivatives were synthesized through a one-pot three-component approach using HAp-encapsulated-γ-Fe2O3[γ-Fe2O3@HAp-SO3H]catalyzed condensation of 6-arnino-2-（methylthio or ethylthio）p...Novel pyrido[2,3-d]pyrimidine derivatives were synthesized through a one-pot three-component approach using HAp-encapsulated-γ-Fe2O3[γ-Fe2O3@HAp-SO3H]catalyzed condensation of 6-arnino-2-（methylthio or ethylthio）pyrimidin-4（3H）-one,Meldrum＇s acid and aryl aldehydes at 60 ℃ and under solvent-free conditions.In this protocol the use of nanocatalyst provided a green,useful and rapid method to generate the products in short reaction times and excellent yields（88%-94%）.展开更多
In our efforts to identify novel potent anticancer agents, we synthesized a series of 2,7-disubstituted triazolo[1,5-a]pyrimidines （6-16）. Their antiproliferative activity against Bel-7402, HT- 1080 and WI-38 cell l...In our efforts to identify novel potent anticancer agents, we synthesized a series of 2,7-disubstituted triazolo[1,5-a]pyrimidines （6-16）. Their antiproliferative activity against Bel-7402, HT- 1080 and WI-38 cell lines was tested by MTT assay in vitro. Four of the compounds （9-11 and 16） displayed promising antiproliferative activity superior to gefitinib, especially compound 9. A preliminary SAR study of these derivatives was performed.展开更多
This letter describes a simple and efficient synthesis of 3-（cyclohexylamino）-7-hydroxy-2-arylimi- dazo[1,2-c]pyrimidin-5（6H）-one via a one-pot three-component reaction of cyclohexyl isocyanide, an aldehyde, and 4...This letter describes a simple and efficient synthesis of 3-（cyclohexylamino）-7-hydroxy-2-arylimi- dazo[1,2-c]pyrimidin-5（6H）-one via a one-pot three-component reaction of cyclohexyl isocyanide, an aldehyde, and 4-amiopyrimidine-2,6-diol in the presence of a catalytic amount of SSA.展开更多
A concise and efficient approach was developed for the synthesis of mono-substituted and di-substituted pyrimidines products via palladium-catalyzed amination of chloro-substituted 5-nitropyrimidines and amines. This ...A concise and efficient approach was developed for the synthesis of mono-substituted and di-substituted pyrimidines products via palladium-catalyzed amination of chloro-substituted 5-nitropyrimidines and amines. This synthetic methodology can produce various di-substituted pyrimidines in high yields with good functional group tolerance, and provide a complementary tool for the syntheses of important intermediates of nucleosides and purines with bioactivities.展开更多
A series of 2,6-disubstituted-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and their cytotoxic activity against H460, HT-29, MDA-MB-231, U87MG and H1975 cancer cell lines were evaluated in vitro. M...A series of 2,6-disubstituted-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and their cytotoxic activity against H460, HT-29, MDA-MB-231, U87MG and H1975 cancer cell lines were evaluated in vitro. Most of the target compounds exhibited moderate to excellent activity to the tested cell lines. The most promising compound 23 （0.84 μmol/L, 0.23 μmol/L, 2.52 μmogL, 1.80 μmol/L） was 1.0, 2.9, 29.3 and 4.3 times more active than GDC-0941 （0.87 μ mol/L, 0.66μmol/L, 73.8 μmol/L, 7.77 μmol/L） against H460, HT-29, MDA-MB-231 and U87MG cell lines, respectively.展开更多
Two series of thieno[2,3-d]pyrimidine derivatives were designed and synthesized, in which bioactive α-aminophosphonate subunits were introduced at the N3 position through an N-N bond connection. The in vitro cytotoxi...Two series of thieno[2,3-d]pyrimidine derivatives were designed and synthesized, in which bioactive α-aminophosphonate subunits were introduced at the N3 position through an N-N bond connection. The in vitro cytotoxic activity of the novel compounds was tested against human esophageal carcinoma cells （EC109）, human hepatocarcinoma cells （HepG2）, human gastric carcinoma cells （MGC-803）, respectively, by the MTT method. The evaluation results revealed that compounds fimb, 6mf, 6mg, 6rid and 6nh exerted the most potent inhibition against HepG2, MGC-803 and EC109 cells, respectively. In particular, compound 6rag presented excellent inhibitory effect against HepG2 （91.2%） and MGC-803 （94.4%） cells.展开更多
Pyrimidine derivatives have been reported as neuroprotective agents useful for the treatment of various neurodegenerative disorders. In the present study, several pyrimidine analogues have been evaluated as neuroprote...Pyrimidine derivatives have been reported as neuroprotective agents useful for the treatment of various neurodegenerative disorders. In the present study, several pyrimidine analogues have been evaluated as neuroprotective agents in Morris water maze model. It was observed that pyrimidine derivatives 8–17 considerably improve learning, memory, and movement deficits in animal models. Biochemical estimations of brain serum of treated animals revealed suppression of oxidative and nitrosative stress, acetylcholinesterase activity, and other parameters which leads to neurodegeneration of brain. Of all the pyrimidine derivatives, thiomorpholine derivative 8 and piperazine ethanol derivative 17 were found to be the most active neuroprotective agents and produced effects comparable to standard drug rivastigmine in terms of behavioral, biochemical, and molecular aspects.展开更多
New series of pyrazolo[1,5-α]pyrimidine derivatives 7a-i,11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines,namely colorectal car...New series of pyrazolo[1,5-α]pyrimidine derivatives 7a-i,11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines,namely colorectal carcinoma（HCT116）,prostate adenocarcinoma（PC-3） and liver carcinoma（HepG-2） using MTT cytotoxicity assay at 100 μg/mL.Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells.Whereas,compounds 7d and 11 a showed better antitumor activity than the rest of the compounds against both cell lines.A structure-activity relationship（SAR） has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data（MS,IR,^1H NMR and ^13C NMR） and elemental analysis.展开更多
An efficient procedure for N-alkylation of pyrimidines and purines in the presence of tetra-n-butylammonium hydroxide（TBAH） is described. The method is very practical and the alkylation can occur at room temperature...An efficient procedure for N-alkylation of pyrimidines and purines in the presence of tetra-n-butylammonium hydroxide（TBAH） is described. The method is very practical and the alkylation can occur at room temperature and the yields of the N-alkyl pyrimidines and purines were found to be excellent.展开更多
A series of diheterocyclic compounds containing 1,2,4-triazolo [1,5-a]pyrimidine and 1, 3,4-oxadiazole were designed and synthesized starting from 2-mercapto-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine. The structure...A series of diheterocyclic compounds containing 1,2,4-triazolo [1,5-a]pyrimidine and 1, 3,4-oxadiazole were designed and synthesized starting from 2-mercapto-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine. The structure of all compounds prepared were confirmed by H-1 NMR spectroscopy and elemental analysis. The preliminary bioassay indicated that the title compounds displayed good fungicidal activity against Rhizoctonia solani.展开更多
Ethyl 7-aryl-2-benzyhhiopyrazolo [ 1,5-a ] pyrimidine-3-carboxylates （3a-3f） were conveniently synthesized through the reactions of enaminones with 5-amino-3-benzyhhio4-ethoxycarbonyl-1 H-pyrazole in good yields and...Ethyl 7-aryl-2-benzyhhiopyrazolo [ 1,5-a ] pyrimidine-3-carboxylates （3a-3f） were conveniently synthesized through the reactions of enaminones with 5-amino-3-benzyhhio4-ethoxycarbonyl-1 H-pyrazole in good yields and high regioselectivity. The structures of the new compounds were fully characterized by spectroscopic measurmehts, elemental analysis and X-ray diffraction analysis. A plausible reaction mechanism for the formation of the title compounds was also presented.展开更多
A formal[3+3]annulation of 3-aminopyrazoles with cinnamaldehydes or cinnamyl alcohols mediated by NH_(4)SCN has been developed.This protocol provides a practical route to construct 5-arylated pyrazolo[1,5-a]pyrimidine...A formal[3+3]annulation of 3-aminopyrazoles with cinnamaldehydes or cinnamyl alcohols mediated by NH_(4)SCN has been developed.This protocol provides a practical route to construct 5-arylated pyrazolo[1,5-a]pyrimidines with high functional group tolerance.The use of NH_(4)SCN as the cyanide anion surrogate allows the transient generation of cyanohydrin,which shifts the reactive center within cinnamaldehydes from formyl group to alkene group to realize an opposite regiocontrol comparing with previous reports.展开更多
Extensive structure-activity relationships(SARs)study of JND3229 was conducted to yield a series of new reve rsible 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidine privileged scaffold as EGFRC797 S inhibitors.One of the mo...Extensive structure-activity relationships(SARs)study of JND3229 was conducted to yield a series of new reve rsible 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidine privileged scaffold as EGFRC797 S inhibitors.One of the most potent compound 6 i potently suppressed EGFRL858 R/T790 M/C797 S kinase with an IC50 value of 3.1 nmol/L,and inhibited the proliferation of BaF3 cells harboring EGFRL858 R/T790 M/C797 S and EGFR19 D/T790 M/C797 S mutants with IC50 values of 290 nmol/L and 316 nmol/L,respectively.Further,6 i dose-dependently induced suppression of the phosphorylation of EGFRL858 R/T790 M/C797 S and EGFR19 D/T790 M/C797 S in BaF3 cells.Compound 6 i may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer(NSCLC)patients.展开更多
The Biginelli-type compounds 4,5,8a-triarylhexahydropyrimido[4,5-d]pyrimidine-2,7（1H,3H）-diones were synthesized by a one-pot three-component reaction using sulfated tin oxide as a reusable catalyst. This method has...The Biginelli-type compounds 4,5,8a-triarylhexahydropyrimido[4,5-d]pyrimidine-2,7（1H,3H）-diones were synthesized by a one-pot three-component reaction using sulfated tin oxide as a reusable catalyst. This method has the advantages of high yields, short reaction time, simple starting materials and reusability of catalyst for several times.展开更多
文摘Condensation of β-Oxoanilide 1 with active methylene derivatives 2a,bafforded the pyridine derivative 5, and with crotononitrile afforded the pyridine 8. Compounds 9 and 11a-c were obtained by reaction of 1 with malononitrile dimer and arylidinemalononitrile 10a-10c. In contrast, when compound 1 reacted with ethoxymethylen malononitrile afforded the pyridine derivative 13. On the other hand, treatment of 1 with anthranilic acid gave the quinoline derivative 14. Also, reactions of 1 with isothiocyanate derivatives afforded compounds 16-18. The reaction of 1 with chalcone derivative afforded the pyridine derivative 22. Treatment of compound 1 with thiourea produced pyrimidine derivative 23. Furthermore, compound 1 converted into pyrimidinethione 24a and pyrimidinone 24b on treatment with a mixture of aromatic aldehydes and thiourea or urea respectively. Reaction of 24a with hydrazonyl halide, thiosemicarbazide and arylidinecyanothioacetamide afforded compounds 26, 28 and 29. Compound 29 was treated with chloroacetonitrile to afford compound 30. Six compounds from the newly synthesized were screened for antibacterial and antifungal activity against bacteria staphylococcus aureus, bacillus cereus and klebsiella pneumonia and fungi aspergillus flavus and aspergillus ochraceous, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, 1H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.
基金the Department of Chemistry and the office of gifted students at Semnan University for their financial support
文摘The magnetic nanoparticles supported silica sulfuric acid was used as an efficient catalyst for the synthesis of pyrimido[4,5-b]quinoIines and indeno fused pyrido（2,3-d]pyrimidines in water.The desired products were obtained in excellent yields.Fe_3O_4@SiO_2-SO_3H was readily recovered using an external magnet and could be reused several times without significant loss of reactivity.
文摘Room temperature ionic liquids were used as a "green" recyclable alternative to conventional solvents in the synthesis of pharmaceutically useful compounds 2-arylimidazo[1, 2-a] pyrimidines through Tschotschibabin reaction of a-bromoacetophenones with 2-aminopyrimidine in good yields.
文摘A new synthetic strategy for the synthesis of novel 3-（3-（3-methyl-4-nitroisoxazol-5-yl）-2-phenyl-1-（5,7-diaryl-7H-thia- zolo[3,2-a]pyrimidin-3-yl）propyl）-5,7-diaryl-7H-thiazolo[3,2-a]pyrimidines （7a-i） analogues is described. Reaction of 3-（2- （3-methyl-4-nitroisoxazole-5-yl）-l-phenylethyl）pentane-2,4-dione （3） with two moles of thiourea in presence of iodine and CuO afforded 4-（1-（2-aminothiazol-4-yl）-3-（3-methyl-4-nitroisoxazol-5-yl）-2-aryl propylthiazol-2-amine （5）. Compound 5 on reaction with two moles of chalcone （6） furnished novel 3-（3-（3-methyl-4-nitroisoxazol-5-yl）-2-phenyl-1-（5,7-diaryl-7H-thiazolo[3,2- a]pyrimidin-3-yl）propyl）-5,7-diaryl-7H-thiazolo[3,2-a ]pyrimidines （Ta-i）.
基金the China Postdoctoral Science Foundation Funded Project (No. 2014M562165)Jiangxi Natural Science Foundation (Nos. 20133BCB24011, 20141BBG70070 and 20151BAB203011)the Science Foundation of Jiangxi Provincial Department of Education (No. Gjj4669) for support of this research
文摘A direct metal-free C-H amination reaction of cinnamaldehydes and amidines to realize the synthesis of polysubstituted pyrimidines was developed in the presence of base. This greener synthetic methodology provides a straightforward approach to the synthesis of a variety of pyrimidine derivatives under mild reaction condition using oxygen as sole oxidants.
文摘＂Why do arginine and pyrimidines have to be considered together？＂ This was the question I asked when I was invited by Barbara Zimmermann to attend the 23rd Intemational Conference on Arginine and Pyrimidines （ICAP） three years ago. The meeting was held in the summer of 2012 at Bogota, Columbia, known as the ＂the Athens of South America＂. I am not alone in wanting to know more about the relationship between arginine and pyrimidines. Last summer, when ! was organising the next ICAP meeting at Oxford （Aughey et al., 2014）, one of my colleagues asked me, ＂Why such a weird name for a conference？＂ I am not sure if I had given her a satisfying answer and I was enthused to find out what the reasons may be.
基金the Research Council of University of Guilan for the financial support of this research work
文摘Novel pyrido[2,3-d]pyrimidine derivatives were synthesized through a one-pot three-component approach using HAp-encapsulated-γ-Fe2O3[γ-Fe2O3@HAp-SO3H]catalyzed condensation of 6-arnino-2-（methylthio or ethylthio）pyrimidin-4（3H）-one,Meldrum＇s acid and aryl aldehydes at 60 ℃ and under solvent-free conditions.In this protocol the use of nanocatalyst provided a green,useful and rapid method to generate the products in short reaction times and excellent yields（88%-94%）.
文摘In our efforts to identify novel potent anticancer agents, we synthesized a series of 2,7-disubstituted triazolo[1,5-a]pyrimidines （6-16）. Their antiproliferative activity against Bel-7402, HT- 1080 and WI-38 cell lines was tested by MTT assay in vitro. Four of the compounds （9-11 and 16） displayed promising antiproliferative activity superior to gefitinib, especially compound 9. A preliminary SAR study of these derivatives was performed.
基金the Research Council of Shahrood University of Technology for the financial support of this work
文摘This letter describes a simple and efficient synthesis of 3-（cyclohexylamino）-7-hydroxy-2-arylimi- dazo[1,2-c]pyrimidin-5（6H）-one via a one-pot three-component reaction of cyclohexyl isocyanide, an aldehyde, and 4-amiopyrimidine-2,6-diol in the presence of a catalytic amount of SSA.
基金financially supported by the National Natural Science Foundation of China(No.21202116)Independent Innovation Foundation of Tianjin Universityof China(No.2016XZC-0071)Natural Science Foundation of Tianjin of China(No.16JCYBJC20300)
文摘A concise and efficient approach was developed for the synthesis of mono-substituted and di-substituted pyrimidines products via palladium-catalyzed amination of chloro-substituted 5-nitropyrimidines and amines. This synthetic methodology can produce various di-substituted pyrimidines in high yields with good functional group tolerance, and provide a complementary tool for the syntheses of important intermediates of nucleosides and purines with bioactivities.
基金supported by a Grant from the Doctoral Startup Foundation of Liaoning Province(No.20101110)
文摘A series of 2,6-disubstituted-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and their cytotoxic activity against H460, HT-29, MDA-MB-231, U87MG and H1975 cancer cell lines were evaluated in vitro. Most of the target compounds exhibited moderate to excellent activity to the tested cell lines. The most promising compound 23 （0.84 μmol/L, 0.23 μmol/L, 2.52 μmogL, 1.80 μmol/L） was 1.0, 2.9, 29.3 and 4.3 times more active than GDC-0941 （0.87 μ mol/L, 0.66μmol/L, 73.8 μmol/L, 7.77 μmol/L） against H460, HT-29, MDA-MB-231 and U87MG cell lines, respectively.
基金supported by the National Natural Sciences Foundations of China (Nos.21171149,21105091)
文摘Two series of thieno[2,3-d]pyrimidine derivatives were designed and synthesized, in which bioactive α-aminophosphonate subunits were introduced at the N3 position through an N-N bond connection. The in vitro cytotoxic activity of the novel compounds was tested against human esophageal carcinoma cells （EC109）, human hepatocarcinoma cells （HepG2）, human gastric carcinoma cells （MGC-803）, respectively, by the MTT method. The evaluation results revealed that compounds fimb, 6mf, 6mg, 6rid and 6nh exerted the most potent inhibition against HepG2, MGC-803 and EC109 cells, respectively. In particular, compound 6rag presented excellent inhibitory effect against HepG2 （91.2%） and MGC-803 （94.4%） cells.
文摘Pyrimidine derivatives have been reported as neuroprotective agents useful for the treatment of various neurodegenerative disorders. In the present study, several pyrimidine analogues have been evaluated as neuroprotective agents in Morris water maze model. It was observed that pyrimidine derivatives 8–17 considerably improve learning, memory, and movement deficits in animal models. Biochemical estimations of brain serum of treated animals revealed suppression of oxidative and nitrosative stress, acetylcholinesterase activity, and other parameters which leads to neurodegeneration of brain. Of all the pyrimidine derivatives, thiomorpholine derivative 8 and piperazine ethanol derivative 17 were found to be the most active neuroprotective agents and produced effects comparable to standard drug rivastigmine in terms of behavioral, biochemical, and molecular aspects.
文摘New series of pyrazolo[1,5-α]pyrimidine derivatives 7a-i,11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines,namely colorectal carcinoma（HCT116）,prostate adenocarcinoma（PC-3） and liver carcinoma（HepG-2） using MTT cytotoxicity assay at 100 μg/mL.Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells.Whereas,compounds 7d and 11 a showed better antitumor activity than the rest of the compounds against both cell lines.A structure-activity relationship（SAR） has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data（MS,IR,^1H NMR and ^13C NMR） and elemental analysis.
基金Supported by the National Natural Science Foundation of China(No. 20172007) and the"985"Programs, Ministry of Educa-tion of China
文摘An efficient procedure for N-alkylation of pyrimidines and purines in the presence of tetra-n-butylammonium hydroxide（TBAH） is described. The method is very practical and the alkylation can occur at room temperature and the yields of the N-alkyl pyrimidines and purines were found to be excellent.
基金The project was supported by the NNSF of China (Grant No. 29802002) the NSF of Hubei Province the Dawn Plan of Science and Technology for Young Scientists of Wuhan City and Foundation for University Key Teacher by the Ministry of Education of China.
文摘A series of diheterocyclic compounds containing 1,2,4-triazolo [1,5-a]pyrimidine and 1, 3,4-oxadiazole were designed and synthesized starting from 2-mercapto-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine. The structure of all compounds prepared were confirmed by H-1 NMR spectroscopy and elemental analysis. The preliminary bioassay indicated that the title compounds displayed good fungicidal activity against Rhizoctonia solani.
文摘Ethyl 7-aryl-2-benzyhhiopyrazolo [ 1,5-a ] pyrimidine-3-carboxylates （3a-3f） were conveniently synthesized through the reactions of enaminones with 5-amino-3-benzyhhio4-ethoxycarbonyl-1 H-pyrazole in good yields and high regioselectivity. The structures of the new compounds were fully characterized by spectroscopic measurmehts, elemental analysis and X-ray diffraction analysis. A plausible reaction mechanism for the formation of the title compounds was also presented.
文摘A formal[3+3]annulation of 3-aminopyrazoles with cinnamaldehydes or cinnamyl alcohols mediated by NH_(4)SCN has been developed.This protocol provides a practical route to construct 5-arylated pyrazolo[1,5-a]pyrimidines with high functional group tolerance.The use of NH_(4)SCN as the cyanide anion surrogate allows the transient generation of cyanohydrin,which shifts the reactive center within cinnamaldehydes from formyl group to alkene group to realize an opposite regiocontrol comparing with previous reports.
基金financial support from the National Natural Science Foundation of China(Nos.81922062,81874285 and 81673285)Guangdong International Science and TechnologyCooperation Project(No.2018A050506043)+1 种基金Guangzhou City Key Laboratory of Precision Chemical Drug Development(No.201805010007)Institutes for Drug Discovery and Development of Chinese Academy of Science(No.CASIMM0120185006)。
文摘Extensive structure-activity relationships(SARs)study of JND3229 was conducted to yield a series of new reve rsible 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidine privileged scaffold as EGFRC797 S inhibitors.One of the most potent compound 6 i potently suppressed EGFRL858 R/T790 M/C797 S kinase with an IC50 value of 3.1 nmol/L,and inhibited the proliferation of BaF3 cells harboring EGFRL858 R/T790 M/C797 S and EGFR19 D/T790 M/C797 S mutants with IC50 values of 290 nmol/L and 316 nmol/L,respectively.Further,6 i dose-dependently induced suppression of the phosphorylation of EGFRL858 R/T790 M/C797 S and EGFR19 D/T790 M/C797 S in BaF3 cells.Compound 6 i may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer(NSCLC)patients.
文摘The Biginelli-type compounds 4,5,8a-triarylhexahydropyrimido[4,5-d]pyrimidine-2,7（1H,3H）-diones were synthesized by a one-pot three-component reaction using sulfated tin oxide as a reusable catalyst. This method has the advantages of high yields, short reaction time, simple starting materials and reusability of catalyst for several times.
