Artículos de revistas: "Pyrido[2’,1’ :1,5]pyrazolo[3,4-d]pyrimidine"

1

Abdelhamid, Abdou O. y Sobhi M. Gomha. "Synthesis of New Pyrazolo[1,5-a]pyrimidine, Triazolo[4,3-a]pyrimidine Derivatives, and Thieno[2,3-b]pyridine Derivatives from Sodium 3-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-3-oxoprop-1-en-1-olate". Journal of Chemistry 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/327095.

Texto completo

Resumen

Condensation of sodium 3-oxo-3-(1-phenyl-1H-pyrazol-4-yl)prop-1-en-1-olate (2) with several heterocyclic amines, cyanoacetamide, cyanothioacetamide, and 2-cyanoacetohydrazide gives pyrazolo[1,5-a]pyrimidines (5a–d), pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine (9), benzo[4,5]imidazo[1,2-a]pyrimidine (10), [1,2,4]triazolo[1,5-a]pyrimidine (11), and pyridine derivatives (12–14). Also, thieno[2,3-b]pyridines (15–18) were synthesized via pyridinethione (13) withα-halo ketones andα-halo ester. Structures of the newly synthesized compounds were elucidated by elemental analysis, spectral data, alternative synthetic routes, and chemical transformation whenever possible.

Los estilos APA, Harvard, Vancouver, ISO, etc.

2

Thokchom, Herojit S., Anita D. Nongmeikapam y Warjeet S. Laitonjam. "Synthesis of fused pyrazolo-, isoxazolo-, pyrimido-, and pyridopyrimidines". Canadian Journal of Chemistry 83, n.º 8 (1 de agosto de 2005): 1056–62. http://dx.doi.org/10.1139/v05-054.

Texto completo

Resumen

A systematic study of the synthesis of the 5,7-diaryl-4-oxo-pyrazolo[3,4-d]pyrimidin-6-thiones (3), 2-phenyl-5,7-bis(2′-methylphenyl)-4-oxo-pyrazolo[3,4-d]pyrimidin-6-thiones (4b), 2(3H)-3-phenyl-5,7-diaryl-4-oxo-pyrazolo[3,4-d]pyrimidin-6-thiones (5), 5,7-diaryl-4-oxo-isoxazolo[5,4-d]pyrimidin-6-thiones (7), 3,5,7-triaryl-2,3-dihydro-4-oxo-isoxazalo[5,4-d]pyrimidin-6-thiones (8), 2-amino-6,8-diaryl-5-oxo-pyrimido[4,5-d]pyrimidin-7-thiones (9), 3,4-dihydro-2-amino-4-phenyl-6,8-diaryl-5-oxo-pyrimido[4,5-d]pyrimidin-7-thiones (10), 3-cyano-6,8-diaryl-2,5-dioxo-pyrido[2,3-d]pyrimidin-7-thiones (11) from the condensation products 1 and 2, derived from 1,3-diaryl-2-thiobarbituric acids is described.Key words: synthesis, fused, pyrazole, isoxazole, pyrimidines.

Los estilos APA, Harvard, Vancouver, ISO, etc.

3

Ho, Yuh-Wen y Maw Cherng Suen. "Thioxopyrimidine in Heterocyclic Synthesis I: Synthesis of Some Novel 6-(Heteroatom-substituted)-(thio)pyrimidine Derivatives". Journal of Chemistry 2013 (2013): 1–15. http://dx.doi.org/10.1155/2013/765243.

Texto completo

Resumen

A series of novel N-cycloalkanes, morpholine, piperazines, pyrazole, pyrimidine, benzimidazolo[1,2-a]pyrimidine, 1,2,3,4-tetrazolo[1,5-a]pyrimidine, azopyrazolo[1,5- a]pyrimidine, pyrimido[4', 5':3,4]pyrazolo[1,5-a]pyrimidines and pyridine derivatives incorporating a 5-cyano-4-methyl-2-phenyl-(thio)pyrimidine moiety were obtained by the intramolecular cyclization of 6-methylthio-pyrimidine, 6-(benzoylmethyl)thio- pyrimidine and 2-[(5-cyano-4-methyl-2-phenylpyrimidin-6-yl)thio]-3-dimethyl- amino-1-phenyl-prop-2-en-1-one with appropriate amines and enaminone compounds, respectively. The structure of all new synthesized compounds was established from their spectral data, elemental analysis and the X-ray crystal analysis.

Los estilos APA, Harvard, Vancouver, ISO, etc.

4

Toplak, Renata, Jurij Svete, Simona Golič Grdadolnik y Branko Stanovnik. "Methyl (Z)-2-[(Benzyloxycarbonyl)amino]-3-dimethyl- aminopropenoate in the Synthesis of Heterocyclic Systems. Synthesis of (Benzyloxycarbonyl)amino Substituted Fused Pyrimidinones". Collection of Czechoslovak Chemical Communications 64, n.º 2 (1999): 177–89. http://dx.doi.org/10.1135/cccc19990177.

Texto completo

Resumen

Methyl (Z)-2-[(benzyloxycarbonyl)amino]-3-dimethylaminopropenoate (1) was used as a reagent for preparation of 3-[(benzyloxycarbonyl)amino] substituted 4H-pyrido[1,2-a]pyrimidin-4-ones 17-21, 4H-pyrimido[1,2-b]pyridazin-4-ones 22 and 23, 5H-[1,2,4]triazolo[2,3-a]- pyrimidin-5-one 24, 5H-thiazolo[3,2-a]pyrimidin-5-one 25, and 4H-pyrazino[1,2-a]pyrimidin-4-one 26. Removal of the benzyloxycarbonyl group by catalytical transfer hydrogenation with Pd/C in the presence of cyclohexene is selective to give 3-amino-4H-pyrido[1,2-a]- pyrimidin-4-ones 27-30 in 85-92% yields, or with hydrogen bromide in acetic acid to give 3-amino-4H-pyrimido[1,2-b]pyridazin-4-one (31) and 6-amino-5H-thiazolo[3,2-a]pyrimidin-5-one (32) in 80% yields.

Los estilos APA, Harvard, Vancouver, ISO, etc.

5

Gad-Elkareem, Mohamed A. M., Azza M. Abdel-Fattah y Mohamed A. A. Elneairy. "Pyrazolo[3,4-b]pyridine in heterocyclic synthesis: synthesis of new pyrazolo[3,4-b]pyridines, imidazo[1',2':1,5]pyrazolo[3,4-b]pyridines, and pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidines". Canadian Journal of Chemistry 85, n.º 9 (1 de septiembre de 2007): 592–99. http://dx.doi.org/10.1139/v07-089.

Texto completo

Resumen

Pyrazolo[3,4-b]pyridine derivatives 7 and 9 were synthesized via the reaction of 3-amino-1H-pyrazolo-[3,4-b]pyridine derivative 2 with ω-bromoacetophenones. Reaction of 7 and 9 with Ac2O afforded the imidazo[1',2':1,5]py razolo[3,4-b]pyridine derivative 8 and pyrazolo[3,4-b]pyridine derivative 10, respectively. Reaction of 2 with chloroacetonitrile followed by DMF-DMA gave imidazo[1',2':1,5]pyrazolo[3,4-b]pyridines 4 and 5, respectively. Acetyl acetone and 1,1-dicyano-2,2-dimethylthioethene were reacted with 2 to afford the pyrido[2',3':3,4]pyrazolo-[1,5-a]-pyrimidines 11 and 14, respectively. Also, 2 reacted with DMF-DMA to yield the formamidine 15, which in turn, reacted with active methylene reagents, yielding the corresponding pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidines 18 and 23a-23d.Key words: 1H-pyrazolo[3,4-b]pyridines, imidazo[1',2':1,5]pyrazolo[3,4-b]pyridines, pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidines.

Los estilos APA, Harvard, Vancouver, ISO, etc.

6

Youssef, Ahmed Said Ahmed. "Reactions of 2-amino-4,5,6,7-tetrahydro[1]benzothiophene-3-carbonitrile and 6-amino-1,4-dihydro-3-methyl-1,4-diphenylpyrano[2,3-c]pyrazole-5-carbonitrile with substituted benzylidenemalononitriles, α,β-acetylenic esters and ketones". Journal of Chemical Research 2009, n.º 4 (abril de 2009): 214–17. http://dx.doi.org/10.3184/030823409x435874.

Texto completo

Resumen

Reactions of 2-amino-4,5,6,7-tetrahydro[1]benzothiophene-3-carbonitrile (1a) with substituted benzylidenemalononitriles gave 4-amino-2-(1-cyano-2-arylvinyl)benzothieno[2,3- d]pyrimidine derivatives (3) as ( E,Z)-mixtures and in one case (2c) as separated ( Z)- and ( E)-isomers. Similar treatment of 6-amino-1,4-dihydro-3-methyl-1,4-diphenyl-pyrano[2,3- c]pyrazole-5-carbonitrile (4) yielded similarly-formed pyrazolopyranopyrimidine derivatives (5a, b) as ( Z)-and ( E)-stereoisomers. Attempted acetylation of the aminobenzothienopyrimidines resulted in degradation of the pyrimidine ring and the formation of N-(3-cyano-4,5,6,7-tetrahydro[1]benzothien-2-yl)acetamide (1b). Treatment of 4 with acetylenic esters and ketones (6a-d) afforded the ( Z)-substituted enaminopyrano[2,3- c]pyrazole derivatives. Reacting 1a with aroyl phenyl acetylenes gave by Michael addition the enamino-ketones (8a-c).

Los estilos APA, Harvard, Vancouver, ISO, etc.

7

Kordian, Marcus, Holger Feist, Willi Kantlehner, Manfred Michalik y Klaus Peseke. "Nucleoside Analogues from Push-Pull Functionalized Branched-Chain Pyranosides". Zeitschrift für Naturforschung B 61, n.º 4 (1 de abril de 2006): 406–12. http://dx.doi.org/10.1515/znb-2006-0406.

Texto completo

Resumen

The reaction of methyl 4,6-O-benzylidene-2-deoxy-α-D-erythro-hexopyranosid-3-ulose (1) with ethynylmagnesium bromide in tetrahydrofuran and subsequent trimethylsilylation yielded the methyl 4,6-O-benzylidene-2-deoxy-3-C-ethynyl-3-O-trimethylsilyl-α-D-ribo-hexopyranoside (3). Push-pull functionalization of 3 with N,N,N′,N′,N″,N″-hexamethylguanidinium chloride under basic conditions and following deprotection afforded the spiro{2,5-dihydro-3-dimethylamino- furan-2,8’-4’,4’a,6’,7’,8’,8’a-hexahydro-6’-methoxy-2’-phenyl-pyrano[3,2-d][1.3]dioxine}- 5-ylidenemalononitrile (9). Furthermore, compound 1 reacted with N,N-dimethylformamide dimethylacetal to furnish methyl (E)-4,6-O-benzylidene-2-deoxy-2-dimethylaminomethylene-α-Derythro- hexopyranosid-3-ulose (10). Treatment of 10 with methylhydrazine and amidines yielded (4S,5aR,8R,9aS)-2,5a,6,9a-tetrahydro-4-methoxy-2-methyl-8-phenyl-4H-[1,3]dioxino[4’,5’:5,6]- pyrano[4,3-c]pyrazole (11a) and (2R,4aR,6S,10bS)-4,4a,6,10b-tetrahydro-6-methoxy-2-phenyl- [1,3]dioxino[4’,5’:5,6]pyrano[4,3-d]pyrimidines 12, respectively

Los estilos APA, Harvard, Vancouver, ISO, etc.

8

Tiwari, Sangeeta, Ashok K. Yadav y A. K. Mishra. "Some New Pyrido[2,3-d]pyridimines and their Nucleoside of Biological Importance". E-Journal of Chemistry 7, s1 (2010): S85—S92. http://dx.doi.org/10.1155/2010/812567.

Texto completo

Resumen

Chalcones (I) reacted with malanonitrile and ammonium acetate yielded 2-amino-3-cyano-4,6-disubstituted pyridines (II) in excellent yield. 4-Amino-5,7-disubstituted pyrido [2,3-d]pyrimidine-2(1H)-thiones (III), 4-amino-5,7-disubstituted pyrido[2,3-d]pyrimidines (IV) and 4-imino-3,5,7-trisubstituted pyrido[2,3-d]pyrimidin-2(1H)-ones (V) have been synthesized by the condensation of compound (II) with thiourea, formamide and arylisocynate respectively. The ribofuranosidesviz. 4-amino-5,7-disubstituted-1- [2',3',5'-tri-o-benzoyl-β,D-ribofuranosyl]pyrido[2,3-d]pyrimidine-2-(1H)-thiones (VI) and 4-imino-3,5,7- trisubstituted-1- [2',3',5'-tri-o-benzoyl-β,D-ribofuranosyl] pyrido [2,3-d] pyrimidine-2(1H)-one (VII) were synthesized by converting compounds III and V to trimethylsilyl derivative in situ by reacting them with hexamethyldisilazane to give corresponding ribofuranosides withβ-D-ribofuranose-1-acetate-2,3,5-tribenzoate. Compounds III-V and their ribofuranosides have been screened for antimicrobial and antifungal evaluations.

Los estilos APA, Harvard, Vancouver, ISO, etc.

9

Otero, Iran, Holger Feist, Dirk Michalik, Manfred Michalik, José Quincoces y Klaus Peseke. "Synthesis of Iso-C-nucleoside Analogues from 1-(Methyl 2-O-benzyl-4,6- O-benzylidene-3-deoxy-α-D-altropyranosid-3-yl)but-3-yn-2-ones". Zeitschrift für Naturforschung B 60, n.º 11 (1 de noviembre de 2005): 1175–85. http://dx.doi.org/10.1515/znb-2005-1110.

Texto completo

Resumen

1-(Methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-D-altropyranosid-3-yl)but-3-yn-2-one (3a) reacted with 3-amino-1H-1,2,4-triazole and 5-aminopyrazole-4-carboxylic acid derivatives in the presence of base to furnish the triazolo[1,5-a]pyrimidine (5) and the pyrazolo[1,5- a]pyrimidines (8a - d), respectively. Treatment of 1-(methyl 2-O-benzyl-4,6-O-benzylidene-3- deoxy-α-D-altropyranosid-3-yl)-4-phenyl-but-3-yn-2-one (3b) with cyanacetamide, 2-cyano-N- (4-methoxyphenyl)acetamide und N-aryl-3-oxo-butyramides afforded the substituted nicotinonitriles (11a - d). Furthermore, reaction of 3b with 2-benzimidazolyl-acetonitrile yielded the benz[4,5]imidazo[1,2-a]pyridine-4-carbonitrile (13). Deprotection of 8d in two steps afforded the 2-amino-N-benzyl-5-(methyl 3-deoxy-α-D-altropyranosid-3-yl-methyl)pyrazolo[1,5-a]pyrimidine- 3-carboxamide (10). Compounds 5 and 11d were treated with AcOH/H2O to furnish the 5-(methyl 2-O-benzyl-3-deoxy-α-D-altropyranosid-3-yl-methyl)[1,2,4]triazolo[1,5-a]pyrimidine (6) and the 3-acetyl-1,2-dihydro-1-(4-methoxyphenyl)-6-(methyl 2-O-benzyl-3-deoxy-α-D-altropyranosid-3-ylmethyl)- 4-phenylpyridin-2-one (12), respectively.

Los estilos APA, Harvard, Vancouver, ISO, etc.

10

Abass, Mohamed, Mostafa Ismail, Wafaa Abdel-Monem y Aisha Mayas. "Substituted pyridopyrimidinones, Part IV: 2-chloro-4h-pyrido[1,2-a]pyrimidin-4-one as a synthone of some new heterotricycles". Journal of the Serbian Chemical Society 75, n.º 1 (2010): 11–17. http://dx.doi.org/10.2298/jsc1001011a.

Texto completo

Resumen

2-Chloro-4H-pyrido[1,2-a]pyrimidin-4-one (1) was utilized as a synthone precursor to prepare novel heterotricyclic systems. 2-Azido and 2-hydrazino derivatives (2 and 3) were obtained by nucleophilic replacement evolving compound 1. The hydrazine derivative 3 was transformed into the azido derivative 2 by nitrosation. Treatment of compound 3 with [bis(methylthio)methylene] malononitrile afforded 2-pyrazolylpyridopyrimidine 4. When compound 1 was reacted with 5-amino-3-(methylthio)-1H-pyrazole-4-carbonitrile, the same compound 4 was obtained with no evidence for the production of (pyrazolylamino) pyridopyrimidine 5 or pyrazolodipyridopyrimidine 6. Poly-functionalized dipyridopyrimidine 8 was obtained by reaction of compound 1 with 2-[(methylthio)-( phenylamino)methylene]propanedinitrile. Cyanoguanidine was reacted with compound 1 to afford N-pyridopyrimidinylguanidine 9, which was subjected to cyclization reaction, in presence of piperidinium acetate, to give pyridopyrimidopyrimidine 10.

Los estilos APA, Harvard, Vancouver, ISO, etc.

11

Bahashwan, Saleh A. "Pharmacological activities of some triazinopyrazolothieno pyrimidine derivatives". Acta Pharmaceutica 67, n.º 3 (1 de septiembre de 2017): 407–14. http://dx.doi.org/10.1515/acph-2017-0022.

Texto completo

Resumen

Abstract Triazinopyrazolothieno pyrimidine derivatives 1–5 were evaluated for their anti-inflammatory, analgesic and anticancer activities and acute toxicity. Anti-inflammatory activity of the compounds was studied using the carrageenan test. All tested compounds showed analgesic activity, 3-methoxycarbonyl-4,6-dimethyl-8-[(N-methylindolyl)methyl] pyrimido [5′,4′:4,5]thieno [3′,2′-3,4]pyrazolo [5,1-c]triazine (4) showed activity comparable to that of diclofenac. Compounds 1–5 were also screened for anticancer activity on a human lung cancer cell line (A549) and a human prostate cancer cell line (DU145) using the MTT micro-cultured tetrazolium assay method. Compound 4 showed also significant anticancer activity against both cancer cell lines, comparable to that of doxorubicin. The most active compounds were tested for their acute toxicity and median lethal doses were evaluated.

Los estilos APA, Harvard, Vancouver, ISO, etc.

12

Abdelhamid, Abdou O., Zeineb H. Ismail y Anhar Abdel-Aziem. "Reactions with Hydrazonoyl Halides 601: Synthesis of Thieno[2′,3′:4,5] Pyrimidino[1,2-b][1,2,4,5]tetrazines, [1]benzothieno[2′,3′:4,5]pyrimidino [1,2-b][1,2,4,5]tetrazines, Pyrazolo[3′,4′:4,5]pyrimidino[1,2-b] [1,2,4,5]tetrazines and Pyrazolo[3,4-d]pyridazines". Journal of Chemical Research 2007, n.º 10 (octubre de 2007): 609–16. http://dx.doi.org/10.3184/030823407x256118.

Texto completo

Resumen

Thieno[2′,3′:4,5]pyrimidino[1,2- b][1,2,4,5]tetrazine, [1]benzothieno-[2′,3′:4,5]pyrimidino[1,2- b][1,2,4,5]tetrazine, pyrazolo [3′,4′:4,5]pyrimidino[1,2- b][1,2,4,5]tetrazine, triazolo[4,3- a]pyrimidin-5(1 H)-one, 1-{[2-(1-benzofuran-2-yl)-5-phenyl-4,5-dihydro-1 H-pyrazol-1-yl]-4-substituted-1,3-thiazol-5-yl}-2-phenyldiazene, 3-acyl-4-(1-benzofuran-2-ylcarbonyl) pyrazole and pyrazolo[3,4- d]pyridazine derivatives could be obtained via reactions of hydrazonoyl halides with the appropriate pyrimidine-2-thione, 3-amino-5,6-dimethyl-2-sulfanylthieno[2,3- d]pyrimidin-4(3 H)-one, 5-amino-6-mercapto-1-phenyl-1,5-dihydropyrazolo[3,4- d]pyrimidin-4-one and 1-(benzofuran-2-yl)-3-(dimethylamino)prop-2-en-1-one. Structures of the products have been determined by elemental analyses, spectral data studies and alternative synthesis whenever possible.

Los estilos APA, Harvard, Vancouver, ISO, etc.

13

Hashmi, Imran Ali, Holger Feist, Manfred Michalik, Helmut Reinke y Klaus Peseke. "Dimethylaminomethylene-α-D-xylo-hept-5-ulofuranurononitrile as Building Block in the Synthesis of ‘Reversed’ C-Nucleoside Analogues". Zeitschrift für Naturforschung B 61, n.º 3 (1 de marzo de 2006): 292–300. http://dx.doi.org/10.1515/znb-2006-0309.

Texto completo

Resumen

Abstract 3-O-Benzyl-6-deoxy-1,2-O-isopropylidene-6-(dimethylaminomethylene)-α-D-xylo-hept-5-ulofuranurononitrile (1) was reacted with amidinium salts, S-methylisothiouronium sulfate, and guanidinium chloride, respectively, in the presence of bases to furnish the 4-(3-O-benzyl-1,2-O-isopropylidene- α-D-xylo-tetrofuranos-4-yl)pyrimidine-5-carbonitriles 2 and the 4-(1,2-O-isopropylidene- α-D-glycero-tetr-3-enofuranos-4-yl)pyrimidine-5-carbonitriles 3, respectively. Treatment of 1 with ethyl 5-aminopyrazole-4-carboxylates yielded the ethyl 7-(3-O-benzyl-1,2-O-isopropylidene- α-D-xylo-tetrofuranos-4-yl)-6-cyanopyrazolo[1,5-a]pyrimidine-3-carboxylates 4 and the ethyl 7-amino-6-(3-O-benzyl-1,2-O-isopropylidene-α-D-xylo-pentofuranuronoyl)pyrazolo[1,5-a]pyrimidine- 3-carboxylates 5, respectively. Reaction of 1 with 2-benzimidazolylacetonitrile in the presence of sodium methanolate afforded 1-amino-2-(3-O-benzyl-1,2-O-isopropylidene-α-D-xylo-pentofuranuronoyl) benzo[4,5]imidazo[1,2-a]pyridine-4-carbonitrile (6) and 1-amino-2-(3-deoxy-1,2-O-isopropylidene- α-D-glycero-pent-3-enofuranuronoyl)benzo[4,5]imidazo[1,2-a]pyridine-4-carbonitrile (7).

Los estilos APA, Harvard, Vancouver, ISO, etc.

14

Reheim, Mohamed Ahmed Mahmoud Abdel, Ibrahim Saad Abdel Hafiz y Mohamed Ahmed Elian. "Synthesis and Antimicrobial Evaluation of Some Novel Pyrimidine, Pyrazole, Chromene and Tetrahydrobenzo[b]thiophene Derivatives Bearing Pyrimidinthione Moiety". Current Organic Synthesis 17, n.º 7 (28 de octubre de 2020): 548–57. http://dx.doi.org/10.2174/1570179417666200628021125.

Texto completo

Resumen

Aim and Objective: A novel collection of fused pyrimidine, pyridine, pyrazole, chromene and thiophene derivatives 2-30 have been newly synthesized by using the 1a, b as starting material. Fused pyrane exhibits a range of pharmacological activity such as cancer agents [1], antimicrobial [2-4], antioxidant [5], antiproliferative [6], cytotoxic activity [7], anticipated antitumor [8], antiparkinsonian [9] and anti-inflammatory [10]. Moreover, pyrane derivatives are well known for bacterial biofilm disruptor [11], anticonvulsant [12] and inhibitors of mycobacterium bovis [13]. Materials and Methods: All melting points were measured using the Akofler Block instrument and are uncorrected. IR spectra (KBr) were recorded on a FTIR 5300 spectrometer (υ, cm-1). The 1H-NMR spectra were recorded on a Varian Gemini spectrometer. The 1H-NMR spectra were run at 300, 400 MHz and 13C-NMR spectra were run at 100 MHz in DMSO-d6, CDCl3 as solvents. The chemical shifts are expressed in parts per million (ppm) by using tetramethylsilane (TMS) as an internal reference, 1000 EX mass spectrometer at 70 eV. The purity of synthesized compounds was checked by thin-layer chromatography (TLC) (aluminum sheets) using nhexane, EtOAc (9:1, V/V, 7:3 V/V) eluent. Elemental analyses were carried out by the Microanalytical Research Center, Faculty of Science, and Microanalytical Unit, Faculty of Pharmacy, Cairo University, Egypt. Results and Discussion: A novel series of azoles and azines were designed and prepared via the reaction of 7-amino- 5-(4-chlorophenyl)-4-phenyl-2-thioxo-2,5-dihydro-1H-pyrano- [2,3-d]pyrimidine-6-carbonitrile 1a and 7-amino-4,5- diphenyl-2-thioxo-2,5-dihydro-1H-pyrano[2,3-d]-pyrimidine-6-carbonitrile 1b with some electrophilic and nucleophilic reagents. The structures of target compounds were confirmed by elemental analyses and spectral data. The novel synthesized compounds showed good antimicrobial activity against the previously mentioned microorganisms. Conclusion: In conclusion, compounds 1a, 1b underwent ready cyclization to give fused heterocyclic compounds through reaction with different reagents and under different conditions and subjected to antimicrobial screening.

Los estilos APA, Harvard, Vancouver, ISO, etc.

15

Dashyan, Sh Sh, E. G. Paronikyan, A. S. Noravyan y R. G. Paronikyan. "Synthesis and Anticonvulsive Activity of 5-Pyrrolidin-1-Ylpyrano[4″,3″:4′,5′]Pyrido-3′,2′:4,5]Thieno[3,2-D]Pyrimidine Derivatives". Pharmaceutical Chemistry Journal 50, n.º 4 (agosto de 2016): 221–25. http://dx.doi.org/10.1007/s11094-016-1426-x.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

16

Mahmoud, M. R., A. A. Shalaby, T. A. Gad y A. A. El-Khamry. "A facile synthesis and heteroannulation of pyrido[2,3-d]pyrimidine and related heterocyclic systems". Journal of Chemical Research 2009, n.º 10 (octubre de 2009): 612–15. http://dx.doi.org/10.3184/030823409x12523324765777.

Texto completo

Resumen

7-Amino-1,2,3,4-tetrahydro-4-oxo-2-thioxo-5-(3,4,5-trimethoxyphenyl)pyrido[2,3- d]pyrimidine (1) was prepared and reacted with methyl iodide and ethyl chloroacetate to give the S-alkylated products 2 and 3, respectively. The reaction of 1 or 3 with hydrazine hydrate yielded the same 2-hydrazino derivative 4. Treatment of 4 with 2,4-pentanedione, 2-acetylcyclohexanone and ethyl acetoacetate afforded the corresponding pyrazolylpyrido[2,3- d]pyrimidine derivatives (5–7), while phthalic anhydride gave the phthalazinyl compound 8. Ethoxymethylenemalononitrile with the hydrazine 4 formed the fused 1,2,4-triazepine 9, while triazolopyrido[2,3- d]pyrimidines were obtained from the reaction of 4 with benzylidene malononitrile or benzaldehyde (forming 10), acetic acid/anhydride (giving 11), and ethyl chloroformate (giving 12).

Los estilos APA, Harvard, Vancouver, ISO, etc.

17

Ibrahim, Yusria R. "Synthesis of spiro(cyclohexa-diene-pyrazolo[1,5-a]pyrimidine-4-ylidene)-malononitrile derivatives". Journal of Chemical Research 2009, n.º 8 (agosto de 2009): 495–98. http://dx.doi.org/10.3184/030823409x466717.

Texto completo

Resumen

The reaction of 4-substituted aryldiazenyl-1 H-pyrazole-3,5-diamines with 7,7′,8,8′-tetra-cyanoquinodimethane gave 2-(2′,7′-diamino-6′-cyano-3′-(aryldiazenyl)-4′ H-spiro(cyclohexa[2,5]-diene-1,5′-pyrazolo[1,5- a]pyrimidine-4-ylidene) malononitriles in 63–79% yield, while, by reaction of 2-aminobenzimidazole with 7,7′,8,8′-tetracyanoquinodimethane, 2-(3′-amino-4′-cyano-6′ H-spiro-(cyclohexa[2′,5′]diene-1,5′-benzo( d)-imidazo[1,2- a]pyrimidine)-4-ylidene)malononitrile was formed in 71% yield. Rationales for these transformations are presented.

Los estilos APA, Harvard, Vancouver, ISO, etc.

18

El-Sayed, Wael A., Mahmoud M. M. Ramiz y Adel A. H. Abdel-Rahman. "Anti-Hepatitis B Virus Activity of New N4-β-D-Glycoside Pyrazolo[3,4-d]pyrimidine Derivatives". Zeitschrift für Naturforschung C 64, n.º 5-6 (1 de junio de 2009): 323–28. http://dx.doi.org/10.1515/znc-2009-5-603.

Texto completo

Resumen

1The reaction of 6-hydrazinyl-1,3-dimethylpyrimidine-2,4-(1H,3H)-dione () with ethoxymethylenemalononitrile afforded 5-amino-1-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin- 6-yl)-1H-pyrazole-4-carbonitrile (2). The latter was reacted with formamide and urea affording the corresponding 4-aminopyrazolo[3,4-d]pyrimidines 3 and 4. The reaction of monosaccharide aldoses with 3 and 4 gave stereoselectively the β-N-glycosides 5a - d and 6a - d which were treated with acetic anhydride in pyridine to afford the corresponding acetylated derivatives 7a - d and 8a - d. The prepared compounds were tested for their antiviral activity against hepatitis B virus (HBV) and showed moderate to high activities

Los estilos APA, Harvard, Vancouver, ISO, etc.

19

Zhu, Xiao-Tong, Ge Zhang y Ning Ma. "2-Amino-5,7-bis(4-fluorophenyl)-1′,3′-dimethyl-7,8-dihydrospiro[pyrido[2,3-d]pyrimidine-6(5H),5′-pyrimidine]-2′,4,4′,6′(3H,1′H,3′H,5′H)-tetraone ethanol solvate". Acta Crystallographica Section E Structure Reports Online 65, n.º 7 (20 de junio de 2009): o1625. http://dx.doi.org/10.1107/s1600536809022946.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

20

Ebrahimpour, Zahra, Ali Shiri, Mehdi Bakavoli, Seyed Mohammad Seyedi, Masoumeh Bahreini y Fatemeh Oroojalian. "Microwave-assisted synthesis and antibacterial evaluation of new derivatives of 1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one". Heterocyclic Communications 22, n.º 1 (1 de febrero de 2016): 49–53. http://dx.doi.org/10.1515/hc-2015-0145.

Texto completo

Resumen

AbstractSynthesis of new 1,2-dihydro-3H-pyrazolo[3,4-d] pyrimidin-3-ones4–6starting with ethyl 4-hydroxy-2-methylthio-pyrimidine-5-carboxylate (1) under classical heating and microwave-induced conditions is reported. The antibacterial activities of the synthesized compounds were evaluated using chloramphenicol and streptomycin as reference drugs.

Los estilos APA, Harvard, Vancouver, ISO, etc.

21

Sirakanyan, Samvel N., Domenico Spinelli, Athina Geronikaki, Victor G. Kartsev, Hrachya M. Stepanyan, Elmira K. Hakobyan y Anush A. Hovakimyan. "Synthesis and antimicrobial evaluation of novel polyheterocyclic systems derived from cyclopenta[4',5']pyrido[3',2':4,5]furo[3,2-d]pyrimidine". Chemistry of Heterocyclic Compounds 57, n.º 1 (enero de 2021): 75–80. http://dx.doi.org/10.1007/s10593-021-02870-1.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

22

Hafez, Hend N., Abdulrahman G. Alshammari y Abdel-Rhman B. A. El-Gazzar. "Facile heterocyclic synthesis and antimicrobial activity of polysubstituted and condensed pyrazolopyranopyrimidine and pyrazolopyranotriazine derivatives". Acta Pharmaceutica 65, n.º 4 (1 de diciembre de 2015): 399–412. http://dx.doi.org/10.1515/acph-2015-0037.

Texto completo

Resumen

Abstract Reaction of 6-amino-3-methyl-4-(substituted phenyl)-1,4- dihydropyrano[2,3-c]pyrazole-5-carbonitrile (1) with triethylorthoformate followed by treatment with hydrazine hydrate, formic acid, acetic acid, phenylisocyanate, ammonium thiocyanate and formamide afforded the corresponding pyranopyrimidine derivatives 2-6. Cyclocondensation of 1 with cyclohexanone afforded pyrazolopyranoquinoline 7. One-pot process of diazotation and de-diazochlorination of 1 afforded pyrazolopyranotriazine derivative 8, which upon treatment with secondary amines afforded 9 and 10a- c. Condensation of 2 with aromatic aldehyde gave the corresponding Schiff bases 11a,b, the oxidative cyclization of the hydrazone with appropriate oxidant afforded 11-(4- fluorophenyl))- 2-(4-substituted phenyl)-10-methyl-8,11-dihydropyrazolo-[ 4’,3’:5,6]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidines (12a,b). Structures of the synthesized compounds were confirmed by spectral data and elemental analysis. All synthesized compounds were evaluated for antibacterial and antifungal activities compared to norfloxacin and fluconazole as standard drugs. Compounds 9, 10c, 12a and 15 were found to be the most potent antibacterial agents, with activity equal to that of norfloxacin. On the other hand, compound 5 exhibited higher antifungal activity compared to fluconazole.

Los estilos APA, Harvard, Vancouver, ISO, etc.

23

Aleksanyan, M. S., A. A. Karapetyan, A. Sh Oganisyan y Yu T. Struchkov. "Crystal and molecular structure of the 1:1 solvate of 6,6-dimethyl-4-oxo-2-N-(3-methyl-5-oxo-4H-pyrazolyl)-5,6-dihydro-8H-pyrano[4′,3′:4,5]thieno[2,3-d]pyrimidine with dimethylsulfoxide". Journal of Structural Chemistry 38, n.º 6 (noviembre de 1997): 989–92. http://dx.doi.org/10.1007/bf02763824.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

24

Blake, James F., Michael Burkard, Jocelyn Chan, Huifen Chen, Kang-Jye Chou, Dolores Diaz, Danette A. Dudley et al. "Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development". Journal of Medicinal Chemistry 59, n.º 12 (7 de junio de 2016): 5650–60. http://dx.doi.org/10.1021/acs.jmedchem.6b00389.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

25

Sakamoto, Miho, Takako Moriyasu, Keiko Minowa, Kiyoko Kishimoto, Hideo Kadoi, Tomoko Hamano y Haruhiko Fukaya. "Structure Elucidation of a Novel Analog of Sildenafil Detected as an Adulterant in a Dietary Supplement Using LC-UV and LC/MS". Journal of AOAC INTERNATIONAL 95, n.º 4 (1 de julio de 2012): 1048–52. http://dx.doi.org/10.5740/jaoacint.11-235.

Texto completo

Resumen

Abstract A sildenafil-related compound was detected in a dietary supplement marketed as an aphrodisiac. The compound was detected during analysis of the dietary supplement using LC-UV and LC/electrospray ionization-MS. The structure of the compound was established using high resolution MS, NMR spectrometry, and X-ray crystal structure analysis. The compound was identified as 5-(5-((3,5-dimethylpiperazin-1-yl)sulfonyl)-2-ethoxyphenyl)-1-methyl-7-((1-methyl-4-nitro-1H-imidazol-5-yl)thio)-3-propyl-1H-pyrazolo[4,3-d] pyrimidine. Based on this structure, the compound was named nitroprodenafil. The dietary supplement was found to contain 90 mg nitroprodenafil/capsule.

Los estilos APA, Harvard, Vancouver, ISO, etc.

26

Vlotides, George, Yen-Hao Chen, Tamar Eigler, Song-Guang Ren y Shlomo Melmed. "Fibroblast Growth Factor-2 Autofeedback Regulation in Pituitary Folliculostellate TtT/GF Cells". Endocrinology 150, n.º 7 (9 de abril de 2009): 3252–58. http://dx.doi.org/10.1210/en.2008-1625.

Texto completo

Resumen

To investigate paracrine regulation of pituitary cell growth, we tested fibroblast growth factor (FGF) regulation of TtT/GF folliculostellate (FS) cells. FGF-2, and FGF-4 markedly induced cell proliferation, evidenced by induction of pituitary tumor transforming gene-1 (Pttg1) mRNA expression and percentage of cells in S phase. Signaling for FGF-2-induced FS cell proliferation was explored by specific pharmacological inhibition. A potent inhibitory effect on FGF-2 action was observed by blocking of Src tyrosine kinase with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d] pyrimidine (≥0.1 μm), followed by protein kinase C (PKC) inhibition with GF109203X. Treatment with FGF-2 (30 ng/ml; 10 min) activated phosphorylation of signal transducer and activator of transcription-3, ERK, stress-activated protein kinase/c-Jun N-terminal kinase, Akt, and focal adhesion kinase. Src inhibition with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d] pyrimidine suppressed FGF-2-induced Akt and focal adhesion kinase, indicating effects downstream of FGF-2-induced Src activation. FGF-2 also markedly induced its own mRNA expression, peaking at 2–4 h, and this effect was suppressed by Src tyrosine kinase inhibition. The PKC inhibitor GF109203X abolished FGF-2 autoinduction, indicating PKC as the primary pathway involved in FGF-2 autoregulation in these cells. In addition to pituitary FGF-2 paracrine activity on hormonally active cells, these results show an autofeedback mechanism for FGF-2 in non-hormone-secreting pituitary FS cells, inducing cell growth and its own gene expression, and mediated by Src/PKC signaling.

Los estilos APA, Harvard, Vancouver, ISO, etc.

27

Teixeira, Cleber E., Fernanda B. M. Priviero y R. Clinton Webb. "Molecular Mechanisms Underlying Rat Mesenteric Artery Vasorelaxation Induced by the Nitric Oxide-Independent Soluble Guanylyl Cyclase Stimulators BAY 41-2272 [5-Cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-4-ylamine] and YC-1 [3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl Indazole]". Journal of Pharmacology and Experimental Therapeutics 317, n.º 1 (13 de diciembre de 2005): 258–66. http://dx.doi.org/10.1124/jpet.105.095752.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

28

Mackay, Kenneth B., Haig Bozigian, Dimitri E. Grigoriadis, Sarah A. Loddick, Gail Verge y Alan C. Foster. "Neuroprotective Effects of the CRF1 Antagonist R121920 after Permanent Focal Ischemia in the Rat". Journal of Cerebral Blood Flow & Metabolism 21, n.º 10 (octubre de 2001): 1208–14. http://dx.doi.org/10.1097/00004647-200110000-00009.

Texto completo

Resumen

The neuroprotective effects of a systemically active, highly selective, corticotropin-releasing factor-1 (CRF1) receptor antagonist, R121920 ((7-(dipropylamino)-2,5-dimethyl-3- [2-(dimethylamino)-5-pyridyl] pyrazolo [1,5-a] pyrimidine), was assessed in two rat models of permanent focal cerebral ischemia, where the middle cerebral artery (MCA) was occluded either through the subtemporal approach or using the intraluminal suture technique. R121920 rapidly crossed the blood–brain barrier after intravenous (IV) bolus administration (10 mg/kg), with peak brain concentrations at 5 minutes (2.26 ± 0.40 μg/mL), which were approximately 2-fold greater than those in plasma (0.98 ± 0.24 μg/mL). Treatment with R121920 (10 mg/kg IV followed by 5 mg/kg subcutaneously at hourly intervals for 4 hours) significantly ( P < 0.001) reduced total (by 40%) and cortical (by 37%) infarct volume at 24 hours after subtemporal MCA occlusion (MCAO). In the intraluminal suture MCAO model, IV administration of R121920 (10 mg/kg) at the time of ischemia onset (and at multiple times thereafter) reduced both hemispheric infarct volume (by 34%, P < 0.001) and brain swelling (by 50%, P < 0.001) when assessed at 24 hours. In this model of focal ischemia, significant reduction ( P < 0.05) in both outcome measures was obtained when R121920 administration was delayed up to 1 hour after MCAO. These results further define the antiischemic properties of selective CRF1 antagonists in two experimental models of permanent focal cerebral ischemia.

Los estilos APA, Harvard, Vancouver, ISO, etc.

29

Laurenzana, Ilaria, Antonella Caivano, Francesco La Rocca, Stefania Trino, Luciana De Luca, Francesca D'Alessio, Cristina Tintori et al. "A Pyrazolo[3,4-d]Pyrimidine Compound Reduces Fyn Phosphorylation and Induces Apoptosis in Large Granular Lymphocyte Leukemia Cells". Blood 126, n.º 23 (3 de diciembre de 2015): 3254. http://dx.doi.org/10.1182/blood.v126.23.3254.3254.

Texto completo

Resumen

Abstract Introduction According to WHO classification, large granular lymphocyte leukemia (LGL leukemia) includes three entities: T-cell LGL leukemia, chronic NK lymphoproliferative disorders (NK-CLPD) and aggressive NK cell leukemia. Since no standard therapies for immature NK cell neoplasms have been established so far and the overall outcomes are dismal, new therapeutic options are needed. A pyrazolo[3,4-d]pyrimidine library of compounds have already been studied in a previous work by Tintori et al. It has been demonstrated that one of these compounds proved to be efficient against some member of Src-family of nonreceptor protein-tyrosine kinases, in particular against Fyn. Its abnormal activity has been shown to be related to various hematological malignancies. In this context we verified the effect of the pyrazolo[3,4-d]pyrimidine 4c compound on LGL leukemia cells and we investigated its mechanism of action. Methods The pyrazolo[3,4-d]pyrimidine 4c compound was tested in a time course MTS test (24, 48, 72 h) at different concentrations (0.1, 0.5, 1, 2, 4, 8, 10 µM) on NK leukemia cells (KHYG1 and NK92), hepatosplenic gamma-delta T cell lymphoma cells (Derl-2 and Derl-7), acute T cell leukemia cells (Jurkat), chronic myeloid leukemia cells (Jurl-MK1), acute myeloid leukemia cells (OCI), multiple myeloma cells (SKM-M1), cervical cancer cells (HeLa) and healthy stem cells (CD34+). Fyn mRNA and protein expression was evaluated in all cell lines by quantitative RT-PCR and western blotting (WB). Fyn mRNA levels were evaluated in cells from 10 healthy controls, 10 T-LGL leukemia, 5 GD-LGL leukemia and 8 NK-CLPD patients by qRT-PCR. Apoptosis and cell cycle studies were performed on KHYG1 after treatment with this compound at 4 µM for 24 h using cytometric analysis by labeling cells with annexin V and propidium iodide. Apoptosis pathway was investigated using proteome profiler human apoptosis array kit; pro-caspase 3, activated caspase 3, Akt and p70S6 kinase were validated by WB. Fyn immunoprecipitation was conducted on treated KHYG1 at 4 µM for 24 h. Results The pyrazolo[3,4-d]pyrimidine 4c compound reduced cell viability in KHYG1 cells (50% of reduction after 24 h of treatment at 4 µM), in Derl-2 cells (about 50% after 72 h at 4 µM), in Derl-7 (about 40% after 72 h at 8 µM), in Jurkat cells (50% after 72 h at 2 µM), in NK92 cells (40% after 72 h at 4 µM). No differences in cell viability were observed in Jurl-MK1, OCI, SKM-M1, HeLa and CD34+. To evaluate Fyn expression level, we performed qRT-PCR and WB showing that both transcript and protein levels were highest in NK and T cells (KHYG1>NK92>Jurkat>Derl-7>Derl-2) compared to other cells. Furthermore, we investigated the viability reduction in treated KHYG1 cells demonstrating that pyrazolo[3,4-d]pyrimidine 4c compound induced 45% of apoptosis caspase-3 mediated and cell cycle arrest in G2/M phase. In these cells we detected a reduction of Fyn phosphorylation after treatment and we also observed a decrease of total levels of Akt and p70S6 kinase, other two protein involved in apoptotic process and cell proliferation. Interestingly, qRT-PCR data showed a significant over-expression of Fyn mRNA level also in T-LGL, GD-LGL and NK-CLPD patients compared to healthy controls (p<0.001). Conclusion In this study we demonstrated a higher Fyn expression in LGL leukemia patients compared to healthy controls. We also demonstrated an apoptotic effect of pyrazolo[3,4-d]pyrimidine 4c compound on NK leukemia cells and we provided in vitro preliminary evidences that Fyn is its possible cellular target. Disclosures Musto: Novartis: Honoraria; Celgene: Honoraria; Sanofi: Consultancy; Genzyme: Consultancy; Sandoz: Consultancy; Janssen: Honoraria; Mundipharma: Honoraria; Roche: Honoraria.

Los estilos APA, Harvard, Vancouver, ISO, etc.

30

Hayallah, Alaa M. "Design, Molecular Modeling and Synthesis of Some New Purine-diones and Pyridopyrimidine-diones with Anticancer Activity". JOURNAL OF ADVANCES IN CHEMISTRY 13, n.º 2 (10 de julio de 2017): 5959–76. http://dx.doi.org/10.24297/jac.v13i12.6043.

Texto completo

Resumen

An olomoucine analogues of 2-[(1-substituted)-2,6-dioxo-2,3,6,7â€“tetrahydro-1H-purin-8-ylsulfanyl]-N-substituted acetamide 6a-g and 7a-g, 1-substituted-8-[2-(4-substituted phenyl)-2-oxoethylsulphanyl]-3,7-dihydro-1H-purine-2,6-diones 9a-g and 10a-g, 3-(2-substituted benzyl)-6-(4-substituted phenyl)-1H-thiazolo[2,3-f]purine-2,4-dione 11a-g and 12a-g and their isosteres 3-substituted benzyl-5-methyl-7-substituted-1H-pyrido[2,3-d]pyrimidine-2,4-dione 13a-c and 14a-c were designed and synthesized. The target compounds 11a-g and 12a-g were prepared by cyclodehydration of 9a-g and 10a-g in PPA, while 13a-c and 14a-c were synthesized by condensation of 6-amino-3-(2-substituted benzyl)-1H-pyrimidine-2,4-dione 1a or 1b and the appropriate acylacetone in glacial acetic acid. Structures of the new compounds were verified on the basis of their IR, 1H NMR, MS, HRMS and elemental analyses. The newly synthesized compounds were tested for their anticancer activity and most of the tested compounds showed good to excellent inhibition activity against the tested human breast cancer cell line MCF-7 in comparison to doxorubicin as a reference drug. KEYWORDS: olomoucine; cyclin-depenent kinase; synthesis; anticancer

Los estilos APA, Harvard, Vancouver, ISO, etc.

31

Abdel-Rahman, Adel A. H., Amira K. F. Shaban, Ibrahim F. Nassar, Dina S. EL-Kady, Nasser S. M. Ismail, Samy F. Mahmoud, Hanem M. Awad y Wael A. El-Sayed. "Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity". Molecules 26, n.º 13 (26 de junio de 2021): 3923. http://dx.doi.org/10.3390/molecules26133923.

Texto completo

Resumen

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-‑C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3',2':4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

Los estilos APA, Harvard, Vancouver, ISO, etc.

32

Hu, Xiao-Fen, Ya-Qing Feng, Qi Su y Kang-Jian Qiao. "7′′-Benzyl-9′′-benzylidene-4′-[4-(dimethylamino)phenyl]-1′-methyl-5′′-phenyl- 2′′,3′′,6′′,7′′,8′′,9′′-hexahydro-1H-indole-3(2H)-spiro-2′-pyrrolidine-3′-spiro-2′′-pyrido[4,3-d]thiazolo[3,2-a]pyrimidine-2,2′′-dione acetonitrile disolvate". Acta Crystallographica Section E Structure Reports Online 61, n.º 6 (21 de mayo de 2005): o1830—o1832. http://dx.doi.org/10.1107/s1600536805015485.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

33

Saberi, Dariush, Mohammad Reza Mohammadizadeh y Reza Esmaeili. "Diastereoselective and Efficient Synthesis of Indeno[2″,1″: 4′,5′]furo[3′,2′: 5,6]pyrido[2,3-d]pyrimidine-2,4,6(1H,3H)-trione and 6-(2,3-Dihydro-2-hydroxy-1,3-dioxo-1H-inden-2-yl)-5,8-dihydropyrido[2,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione Derivatives". Helvetica Chimica Acta 98, n.º 10 (octubre de 2015): 1411–18. http://dx.doi.org/10.1002/hlca.201500106.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

34

Ludwig, Lynda M., Dorothee Weihrauch, Judy R. Kersten, Paul S. Pagel y David C. Warltier. "Protein Kinase C Translocation and Src Protein Tyrosine Kinase Activation Mediate Isoflurane-induced Preconditioning In Vivo". Anesthesiology 100, n.º 3 (1 de marzo de 2004): 532–39. http://dx.doi.org/10.1097/00000542-200403000-00011.

Texto completo

Resumen

Background The authors tested the hypotheses that protein kinase C (PKC)-specific isoform translocation and Src protein tyrosine kinase (PTK) activation play important roles in isoflurane-induced preconditioning in vivo. Methods Rats (n = 125) instrumented for measurement of hemodynamics underwent 30 min of coronary artery occlusion followed by 2 h of reperfusion and received 0.9% saline (control); PKC inhibitors chelerythrine (5 mg/kg), rottlerin (0.3 mg/kg), or PKC-epsilonV1-2 peptide (1 mg/kg); PTK inhibitors lavendustin A (1 mg/kg) or 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1; 1 mg/kg); mitochondrial adenosine triphosphate-sensitive potassium channel antagonist 5-hydroxydecanote (10 mg/kg); or reactive oxygen species scavenger N-acetylcysteine (150 mg/kg) in the absence and presence of a 30-min exposure to isoflurane (1.0 minimum alveolar concentration) in separate groups. Isoflurane was discontinued 15 min before coronary occlusion (memory period). Infarct size was determined using triphenyltetrazolium staining. Immunohistochemistry and confocal microscopic imaging were performed to examine PKC translocation in separate groups of rats. Results Isoflurane significantly (P < 0.05) reduced infarct size (40 +/- 3% [n = 13]) as compared with control experiments (58 +/- 2% [n = 12]). Chelerythrine, rottlerin, PKC-epsilonV1-2 peptide, lavendustin A, PP1, 5-hydroxydecanote, and N-acetylcysteine abolished the anti-ischemic actions of isoflurane (58 +/- 2% [n = 8], 50 +/- 3% [n = 9], 53 +/- 2% [n = 9], 59 +/- 3% [n = 6], 57 +/- 3% [n = 7], 60 +/- 3% [n = 7], and 53 +/- 3% [n = 6], respectively). Isoflurane stimulated translocation of the delta and epsilon isoforms of PKC to sarcolemmal and mitochondrial membranes, respectively. Conclusions Protein kinase C-delta, PKC-epsilon, and Src PTK mediate isoflurane-induced preconditioning in the intact rat heart. Opening of mitochondrial adenosine triphosphate-sensitive potassium channels and generation of reactive oxygen species are upstream events of PKC activation in this signal transduction process.

Los estilos APA, Harvard, Vancouver, ISO, etc.

35

Liao, Wu-xiang, Lin Feng, Jing Zheng y Dong-bao Chen. "Deciphering Mechanisms Controlling Placental Artery Endothelial Cell Migration Stimulated by Vascular Endothelial Growth Factor". Endocrinology 151, n.º 7 (12 de mayo de 2010): 3432–44. http://dx.doi.org/10.1210/en.2009-1305.

Texto completo

Resumen

Vascular endothelial growth factor (VEGF) stimulated fetoplacental artery endothelial (oFPAE) cell migration and activated multiple signaling pathways including ERK2/1, p38MAPK, Jun N-terminal kinase (JNK1/2), v-Akt murine thymoma viral oncogene homolog 1 (Akt1), and c-Src in oFPAE cells. VEGF-induced cell migration was blocked by specific kinase inhibitors of JNK1/2 (SP600125), c-Src (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d] pyrimidine), and phosphatidylinositol 3-kinase/Akt (wortmannin) but not ERK2/1 (U0126) and p38MAPK (SB203580). VEGF-induced cell migration was associated with dynamic actin reorganization and focal adhesion as evidenced by increased stress fiber formation and phosphorylation of cofilin-1 and focal adhesion kinase (FAK) and paxillin. Inhibition of JNK1/2, c-Src, and phosphatidylinositol 3-kinase/Akt suppressed VEGF-induced stress fiber formation and cofilin-1 phosphorylation. c-Src inhibition suppressed VEGF-induced phosphorylation of focal adhesion kinase, paxillin, and focal adhesion. VEGF-induced cell migration requires endogenous nitric oxide (NO) as: 1) VEGF-stimulated phosphorylation of endothelial NO synthase (eNOS) via activation of Akt, JNK1/2, and Src; 2) a NO donor diethylenetriamine-NO-stimulated cell migration; and 3) NO synthase inhibition blocked VEGF-induced cell migration. Targeted down-regulation and overexpression of caveolin-1 both inhibited VEGF-induced cell migration. Caveolin-1 down-regulation suppressed VEGF-stimulated phosphorylation of Akt, JNK, eNOS, c-Src, and FAK; however, basal activities of c-Src and FAK were elevated in parallel with increased stress fiber formation and focal adhesion. Caveolin-1 overexpression also inhibited VEGF-induced phosphorylation of Akt, JNK, c-Src, FAK, and eNOS. Thus, VEGF-induced placental endothelial cell migration requires activation of complex pathways that are paradoxically regulated by caveolin-1.

Los estilos APA, Harvard, Vancouver, ISO, etc.

36

Tang, Xian-Liang, Eitaro Kodani, Hitoshi Takano, Michael Hill, Ken Shinmura, Thomas M. Vondriska, Peipei Ping y Roberto Bolli. "Protein tyrosine kinase signaling is necessary for NO donor-induced late preconditioning against myocardial stunning". American Journal of Physiology-Heart and Circulatory Physiology 284, n.º 4 (1 de abril de 2003): H1441—H1448. http://dx.doi.org/10.1152/ajpheart.00789.2002.

Texto completo

Resumen

Although protein tyrosine kinases (PTKs) signaling has been implicated in the late phase of ischemic preconditioning (PC), it is unknown whether PTK signaling is necessary for the development of nitric oxide (NO) donor-induced late PC. Thus conscious rabbits underwent a sequence of six 4-min coronary occlusion (O)/4-min reperfusion (R) cycles followed by a 5-h recovery period of reperfusion for 3 consecutive days ( days 1, 2, and 3). On day 0 (24 h before the 6 O/R cycles on day 1), rabbits received no treatment (control), the NO donor diethylenetriamine (DETA)/NO (DETA/NO), the PTK inhibitor 4-amino-5-(4-chlorophenyl)-7-( t-butyl)pyrazolo[3,4- d]pyrimidine (PP2), or DETA/NO plus PP2 (DETA/NO + PP2). In control rabbits ( n = 6), the six O/R cycles on day 1resulted in delayed functional recovery, indicating severe myocardial stunning. In rabbits pretreated with DETA/NO ( n = 5) on day 1, myocardial stunning caused by the six O/R cycles on day 1 was markedly attenuated, with a significant reduction (∼60%) in the total deficit of wall thickening (WTh) compared with controls, indicating that DETA/NO induced a late PC effect against stunning. However, in rabbits pretreated with DETA/NO + PP2 ( n = 5), the total deficit of WTh was significantly greater than that in rabbits treated with DETA/NO alone and was similar to that in controls, indicating that PP2 prevented the development of DETA/NO-induced late PC. In rabbits pretreated with PP2 on day 0 ( n = 4), the total deficit of WTh was similar to that in controls, indicating that PP2 does not affect myocardial stunning in itself. We conclude that a PTK-dependent signaling mechanism is necessary for the development of NO donor-induced late PC against myocardial stunning in conscious rabbits.

Los estilos APA, Harvard, Vancouver, ISO, etc.

37

SHAH, O. Jameel, Scot R. KIMBALL y Leonard S. JEFFERSON. "The Src-family tyrosine kinase inhibitor PP1 interferes with the activation of ribosomal protein S6 kinases". Biochemical Journal 366, n.º 1 (15 de agosto de 2002): 57–62. http://dx.doi.org/10.1042/bj20020198.

Texto completo

Resumen

Considerable biochemical and pharmacological evidence suggests that the activation of ribosomal protein S6 kinases (S6Ks) by activated receptor tyrosine kinases involves multiple co-ordinated input signals. However, the identities of many of these inputs remain poorly described, and their precise involvement in S6K activation has been the subject of great investigative effort. In the present study, we have shown that 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1), a selective inhibitor of the Src family of non-receptor tyrosine kinases, interferes with the activation of 70 and 85kDa S6K gene products (p70S6K1 and p85S6K1) by insulin, insulin-like growth factor 1, sodium orthovanadate and activated alleles of phosphoinositide 3-kinase and H-Ras. PP1 also impedes the activation of AKT/protein kinase B and the extracellular signal-regulated protein kinases 1 and 2 by these various stimuli. Insulin-like growth factor 1 was observed to induce a sustained increase in c-Src autophosphorylation as revealed using anti-phospho-Y416 antisera, but this effect was absent from the cells treated with PP1. To conclude, an activated allele of p70S6K1 is compared with the wild-type allele, resistant to inhibition by PP1 when co-expressed with phosphoinositide-dependent kinase 1 (PDK1), suggesting that PP1 affects p70S6K1 via a PDK1-independent pathway. Thus activation of Src may supply a necessary signal for the activation of p70S6K1 and possibly other S6Ks.

Los estilos APA, Harvard, Vancouver, ISO, etc.

38

Gui, Yu, Xi-Long Zheng y Morley D. Hollenberg. "Interleukin-1β, Src- and non-Src tyrosine kinases, and nitric oxide synthase induction in rat aorta in vitro". American Journal of Physiology-Heart and Circulatory Physiology 279, n.º 2 (1 de agosto de 2000): H566—H576. http://dx.doi.org/10.1152/ajpheart.2000.279.2.h566.

Texto completo

Resumen

We studied the potential roles for endogenous interleukin-1β (IL-1β) and for several signaling pathways in the spontaneous induction in vitro of inducible nitric oxide synthase (iNOS) in endothelium-denuded rat aorta rings. Added IL-1β augmented, whereas the IL-1β receptor antagonist IL-1ra blocked, spontaneous iNOS induction. Furthermore, increases in IL-1β mRNA preceded those of iNOS mRNA. Mitogen-activated protein kinase kinase and phosphatidyl inositol 3′ kinase inhibition did not block iNOS induction, whereas nuclear factor κB inhibition did. The sarcoma virus tyrosine kinase (Src) family-selective inhibitor 4-amino-5(4-methylphenyl)-7-( t-butyl)pyrazolo[3,4-d]pyrimidine (PP1) blocked the upregulation of IL-1β mRNA and the subsequent induction of iNOS but not the induction of iNOS stimulated by exogenously added IL-1β. In contrast, the non-Src inhibitors TP 47/AG 213 and genistein and the tyrosine phosphatase inhibitor vanadate did not affect the spontaneous upregulation of IL-1β mRNA but blocked both the IL-1β-mediated and spontaneous induction of iNOS. We conclude that 1) the upregulation of tissue IL-1β, via a signaling pathway involving a Src family kinase, plays a key role in rat vascular iNOS induction and 2) non-Src tyrosine kinases play roles downstream from IL-1β for iNOS induction.

Los estilos APA, Harvard, Vancouver, ISO, etc.

39

Tozzi, Alessandro, Ezia Guatteo, Luigi Caputi, Giorgio Bernardi y Nicola B. Mercuri. "Group I mGluRs Coupled to G Proteins Are Regulated by Tyrosine Kinase in Dopamine Neurons of the Rat Midbrain". Journal of Neurophysiology 85, n.º 6 (1 de junio de 2001): 2490–97. http://dx.doi.org/10.1152/jn.2001.85.6.2490.

Texto completo

Resumen

Metabotropic glutamate receptors (mGluRs) modulate neuronal function via different transduction mechanisms that are either dependent or independent on G-protein function. Here we investigated, using whole cell patch-clamp recordings in combination with fluorimetric measurements of intracellular calcium concentration ([Ca2+]i), the metabolic pathways involved in the responses induced by group I mGluRs in dopamine neurons of the rat midbrain. The inward current and the [Ca2+]i increase caused by the group I mGluR agonist ( S)-3,5-dihydroxyphenylglycine (DHPG, 100 μM) were permanently activated and subsequently abolished in cells loaded with the nonhydrolizable GTP-analogue GTP-γ-S (600 μM). In addition, when GDP-β-S (600 μM) was dialyzed into the cells to produce the blockade of the G proteins, the DHPG-dependent responses were reduced. When the tissue was bathed with the phospholipase C inhibitor 1-[6[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]exyl]-1H-pyrrole-2,5-dione (10 μM), the DHPG-induced calcium transients slightly diminished but the associated inward currents were not affected. Interestingly, a substantial depression of the DHPG-induced inward current and transient increase of [Ca2+]i was caused by the protein tyrosine kinase inhibitors tyrphostin B52 (40 μM) and 4′,5,7-trihydroxyisoflavone (genistein; 40 μM), whereas genistein's inactive analogue 4′,5,7-trihydroxyisoflavone-7-glucoside (40 μM) was ineffective. The blockade of the Src family of tyrosine kinase by 4-amino-5-(4-methylphenyl)-7-( t-butyl)pyrazolo[3,4-d]pyrimidine (20 μM), mitogen-activated protein kinase by 2′-amino-3′ methoxyflavone (50 μM), and protein kinase C by staurosporine (1 μM) had no effect on the cellular responses caused by DHPG. The mGluR5-selective antagonist 2-methyl-6-(phenylethynyl)-pyridine (10–100 μM) did not affect the actions of DHPG. Thus our results indicate that the responses, mainly mediated by mGluRs1 in dopamine neurons, are activated by intracellular mechanisms coupled to G proteins and regulated by tyrosine kinases.

Los estilos APA, Harvard, Vancouver, ISO, etc.

40

Gao, Ben-Bo, Hans Hansen, Hong-Chi Chen y Edward P. Feener. "Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet-derived growth factor receptor-β and its binding to class IA PI3K in vascular smooth muscle cells". Biochemical Journal 397, n.º 2 (28 de junio de 2006): 337–44. http://dx.doi.org/10.1042/bj20060095.

Texto completo

Resumen

PI3K (phosphoinositide 3-kinase) activity is involved in Ang (angiotensin) II-stimulated VSMC (vascular smooth muscle cell) growth and hypertrophy. In the present study, we demonstrate that the inhibition of PI3K in VSMCs by expression of a dominant-negative p85α mutant lacking the p110-binding domain (Δp85), or by treatment of cells with LY294002, inhibited Ang II-stimulated PAI-1 (plasminogen activator inhibitor-1) mRNA expression. Using a GST (glutathione S-transferase) fusion protein containing the p85 N-terminal SH2 (Src homology 2) domain as ‘bait’ followed by MS/MS (tandem MS), we identified a 70 kDa fragment of the p70 PDGFR-β (platelet-derived growth factor receptor-β) as a signalling adapter that is phosphorylated and recruits the p85 subunit of PI3K after Ang II stimulation of AT1 (Ang II subtype 1) receptors on VSMCs. This fragment of the PDGFR-β, which has a truncation of its extracellular domain, accounted for approx. 15% of the total PDGFR-β detected in VSMCs with an antibody against its cytoplasmic domain. Stimulation of VSMCs with Ang II increased tyrosine-phosphorylation of p70 PDGFR-β at Tyr751 and Tyr1021 and increased its binding to p85. PDGF also induced phosphorylation of p70 PDGFR-β, a response inhibited by the PDGF tyrosine kinase selective inhibitor, AG1296. By contrast, Ang II-induced phosphorylation of the 70 kDa receptor was not affected by AG1296. Ang II-stimulated phosphorylation of the p70 PDGFR-β was blocked by the AT1 receptor antagonist, candesartan (CV 11974) and was partially inhibited by PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine}, an Src family kinase inhibitor. Our result suggests that the p70 PDGFR-β functions as an adapter that recruits PI3K to the membrane upon AT1 receptor stimulation.

Los estilos APA, Harvard, Vancouver, ISO, etc.

41

Gaben, Anne-Marie, Cécile Saucier, Monique Bedin, Gérard Redeuilh y Jan Mester. "Mitogenic Activity of Estrogens in Human Breast Cancer Cells Does Not Rely on Direct Induction of Mitogen-Activated Protein Kinase/Extracellularly Regulated Kinase or Phosphatidylinositol 3-Kinase". Molecular Endocrinology 18, n.º 11 (1 de noviembre de 2004): 2700–2713. http://dx.doi.org/10.1210/me.2003-0133.

Texto completo

Resumen

Abstract We have addressed the question of rapid, nongenomic mechanisms that may be involved in the mitogenic action of estrogens in hormone-dependent breast cancer cells. In quiescent, estrogen-deprived MCF-7 cells, estradiol did not induce a rapid activation of either the MAPK/ERK or phosphatidylinositol-3 kinase (PI-3K)/Akt pathway, whereas the entry into the cell cycle was documented by the successive inductions of cyclin D1 expression, hyperphosphorylation of the retinoblastoma protein (Rb), activity of the promoter of the cyclin A gene, and DNA synthesis. However, pharmacological inhibitors of the src family kinases, 4-amino-5-(4-methylphenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP1) or of the PI-3K (LY294002) did prevent the entry of the cells into the cell cycle and inhibited the late G1 phase progression, whereas the inhibitor of MAPK/ERK activation (U0126) had only a partial inhibitory effect in the early G1 phase. In agreement with these results, small interfering RNA targeting Akt strongly inhibited the estradiolinduced cell cycle progression monitored by the activation of the promoter of the cyclin A gene. The expression of small interfering RNA targeting MAPK 1 and 2 also had a clear inhibitory effect on the estradiol-induced activation of the cyclin A promoter and also antagonized the estradiol-induced transcription directed by the estrogen response element. Finally, transfection of the estrogen receptor into NIH3T3 fibroblasts did not confer to the cells sensitivity to a mitogenic action of estradiol. We conclude that the induction of the cell cycle by estradiol does not require a direct activation of MAPK/ERK or PI-3K signaling protein kinase cascades, but that these kinases appear to have a permissive role in the cell cycle progression.

Los estilos APA, Harvard, Vancouver, ISO, etc.

42

Bhattacharya, Sujoy, Ramesh M. Ray y Leonard R. Johnson. "Integrin β3-mediated Src activation regulates apoptosis in IEC-6 cells via Akt and STAT3". Biochemical Journal 397, n.º 3 (13 de julio de 2006): 437–47. http://dx.doi.org/10.1042/bj20060256.

Texto completo

Resumen

Intestinal epithelial (IEC-6) cells are resistant to apoptosis following the inhibition of ODC (ornithine decarboxylase) and subsequent polyamine depletion. The depletion of polyamines rapidly activates NF-κB (nuclear factor κB) and STAT3 (signal transducer and activator of transcription 3), which is responsible for the observed decrease in apoptosis. Since both NF-κB and STAT3 signalling pathways can be activated by Src kinase, we examined its role in the antiapoptotic response. Inhibition of ODC by DFMO (α-difluoromethylornithine) increased the activity of Src and ERK1/2 (extracellular-signal-regulated kinase 1/2) within 30 min, which was prevented by exogenous polyamines added to the DFMO-containing medium. Conversely, epidermal growth factor-mediated Src and ERK1/2 activation was not prevented by the addition of polyamines. Inhibition of Src with PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine} and a DN-Src (dominant-negative Src) construct prevented the activation of Akt, JAK (Janus kinase) and STAT3. Spontaneous apoptosis was increased in DN-Src-expressing cells and the protective effect of polyamine depletion was lost. Polyamine depletion by DFMO increased integrin β3 Tyr785 phosphorylation. Cells plated on fibronectin had significantly higher β3 phosphorylation and Src activation compared with plastic. Exogenous polyamines added to the fibronectin matrix prevented Src activation. Arg-Gly-Asp-Ser inhibited β3, Src and Akt phosphorylation and sensitized polyamine-depleted cells to tumour necrosis factor α/cycloheximide-mediated apoptosis. Fibronectin activated Src and subsequently protected cells from apoptosis. Together, these results suggest that the inhibition of ODC rapidly removes a small pool of available polyamines triggering the activation of β3 integrin, which in turn activates Src. The subsequent Akt and JAK activation is accompanied by translocation of NF-κB and STAT3 to the nucleus and the synthesis of antiapoptotic proteins.

Los estilos APA, Harvard, Vancouver, ISO, etc.

43

Yano, Naohiro, Daisuke Suzuki, Masayuki Endoh, Andy Tseng, Joan P. Stabila, Bethany G. McGonnigal, Ting C. Zhao, James F. Padbury y Yi-Tang Tseng. "β-Adrenergic Receptor Mediated Protection against Doxorubicin-Induced Apoptosis in Cardiomyocytes: The Impact of High Ambient Glucose". Endocrinology 149, n.º 12 (21 de agosto de 2008): 6449–61. http://dx.doi.org/10.1210/en.2008-0292.

Texto completo

Resumen

Recent studies have demonstrated that the β2-adrenergic receptor (β2AR)-Gαi signaling pathway exerts a cardiac antiapoptotic effect. The goals of this study were to determine the intracellular signaling factors involved in β2AR-mediated protection against doxorubicin-induced apoptosis in H9c2 cardiomyocyte and explore the impact of high ambient glucose on the antiapoptotic effect. Under physiological glucose environment (100 mg/dl), β2AR stimulation prevented doxorubicin-induced apoptosis, which was attenuated by cotreatment with wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, or transfection of a dominant-negative Akt. Inhibition of Src kinase with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d] pyrimidine or cSrc small interfering RNA 32 also attenuated the antiapoptotic effect. Inhibition of platelet-derived growth factor receptor (PDGFR) with AG1296 reversed the β2AR-induced antiapoptotic effect. Transfection of an active Src cDNA (Y529F) alone was sufficient to render the cells resistant to apoptosis, and the resistance was blocked by wortmannin. Transfection of an active PI3K minigene (iSH2-p110) alone also induced resistance to apoptosis, and the resistance was reversed by an Akt-inhibitor but not by AG1296. High ambient glucose (450 mg/dl) caused two major effects: 1) it significantly reduced βAR-induced PDGFR phosphorylation, Src kinase activity, and activation of PI3K signaling pathway; and 2) it partially attenuated β2AR-induced antiapoptotic effect. These data provide in vitro evidence supporting a signaling cascade by which β2AR exerts a protective effect against doxorubicin-induced apoptosis via sequential involvement of Gαi, Gβγ, Src, PDGFR, PI3K, and Akt. High ambient glucose significantly attenuates β2AR-mediated cardioprotection by suppressing factors involved in this cascade including PDGFR, Src, and PI3K/Akt.

Los estilos APA, Harvard, Vancouver, ISO, etc.

44

Kumar, M. Sathish y M. Vijey Aanandhi. "Design, Molecular docking, Synthesis and Biological evaluation of 5, 7 dimethyl pyrido(2, 3-d)pyrimidin-4-one and 4,5 dihydro pyrazolo (3, 4-d) pyrimidines for cytotoxic activity". Research Journal of Pharmacy and Technology, 29 de junio de 2021, 3029–38. http://dx.doi.org/10.52711/0974-360x.2021.00530.

Texto completo

Resumen

The fused pyrimidine derivatives are potent tyrosine kinase and thymidylate synthase inhibitors. The compound 3-(4-sulphonyl amino)-2-methyl thio-6-phenyl azo-5, 7-dimethyl pyrido(2,3-d)pyrimidin-4-one was synthesized from Ethyl 2-amino-4,6-dimethylpyridine-3-carboxylate, benzene diazonium chloride, benzene sulphonyl amino isothiocyanate in subsequent reactions. 1-(1, 3-benzothiazol-2-yl)-3-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidines were synthesized from 1, 3-benzothiazole, 2-thiol, Hydrazine Hydrate, 2-hydrazinyl-1, 3-benzothiazole and aldehydes in subsequent reactions. Twenty-five derivatives pyrimidine scaffolds were designed and performed molecular docking studies for the ability to inhibit the target protein using molecular docking simulation, selective compounds were synthesized and characterized by spectral methods. All the synthesized compounds evaluated for their antioxidant activity and MTT assay exhibited compounds 13c, 13e and 14d can be potential anticancer candidates against MCF-7, Hep G2 and Hela cell lines respectively. Based on all the studies conclude that good agreement was observed between the top-ranked docking scores and top experimental inhibitors when compared with standards ascorbic acid and imatinib. Hence, the compounds could be considered as new anticancer hits for further lead optimization.

Los estilos APA, Harvard, Vancouver, ISO, etc.

45

Ashok, D. y K. Pallavi. "SYNTHESIS OF 1-ARYL-5-METHYL-4-[4-ARYL-6-(3-OXO-1,4-BENZOTHIAZIN-6-YL)PYRID-2-YL]PYRAZOLES AND 1-ARYL-5-METHYL-4-[2-AMINO-4-ARYL-PYRIMIDIN-6-YL]PYRAZOLES AS ANTIBACTERIAL AGENTS". Heterocyclic Communications 14, n.º 1-2 (enero de 2008). http://dx.doi.org/10.1515/hc.2008.14.1-2.33.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

46

"Orphan designation: 2-(isopropylamino)-3-methyl-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one, Treatment of tenosynovial giant cell tumour, localised and diffuse type". Case Medical Research, 24 de febrero de 2020. http://dx.doi.org/10.31525/cmr-2a32a82.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

47

Kim, Tae Woo, Da-Won Hong y Sung Hee Hong. "CB13, a novel PPARγ ligand, overcomes radio-resistance via ROS generation and ER stress in human non-small cell lung cancer". Cell Death & Disease 11, n.º 10 (octubre de 2020). http://dx.doi.org/10.1038/s41419-020-03065-w.

Texto completo

Resumen

Abstract Peroxisome proliferator-activated receptor gamma (PPARγ) is a well-known therapeutic target for type 2 diabetes as well as is a potential target for effective anti-cancer drug, since PPARγ ligands such as ciglitazone (Cig) frequently cause cell death in many types of cancer cells and suppress tumor growth. However, many cancer patients acquire chemo-resistance or radio-resistance after chemo or radiotherapy, and it is still unclear. In the difficulty of well-known anti-cancer drugs, we developed a novel PPARγ agonist CB13 (1-benzyl-5-(4-methylphenyl) pyrido [2,3-d]pyrimidine-2,4(1H,3H)-dione) and investigated the anti-cancer effect and cell death mechanism on human non-small cell lung cancer (NSCLC) cells. With anti-cancer effect of Cig, CB13 also causes inhibition of cell growth by decreasing cell viability, increasing the release of LDH, and increasing caspase-3, and caspase-9 activities. CB13 generates reactive oxygen species (ROS) and causes cell death via ER stress in NSCLC and radio-resistant NSCLC cells (A549R and H460R), and a combination of CB13 and radiation induces greater ER stress and cell death when compared to CB13 alone. Taken together, our results suggest that a combination of CB13 and radiation may overcome radio-resistance caused by radiotherapy.

Los estilos APA, Harvard, Vancouver, ISO, etc.

Artículos de revistas sobre el tema "Pyrido[2’,1’ :1,5]pyrazolo[3,4-d]pyrimidine"

Crea una cita precisa en los estilos APA, MLA, Chicago, Harvard y otros