Design and synthesis of new EGFR- tyrosine kinase inhibitors containing pyrazolo[3,4-pywmidine cores as anticancer agents

New designed EGFR inhibitors [7-1 1] were prepare dfrom the pyrazolo[3t4-d]pyrimidine intermediates 4a-d including different moieties. All newly synthesized compounds were confirmed by elemental analyses and spectral data. The molecular simulation docking to protein tyrosine kinase [EGFR], using erlotinib [Tarceva[TM]] as a lead compound was also studied. Some of the prepared compounds were screened for in-vitro cytotoxic activity. The docking results were in coincidence with the biological results that indicated compound 7a showed an inhibitory activity against human breast carcinoma cell line [MCF-7] [1C so [14.86microM]

Microwave mediated facile synthesis of some novel pyrazole, pyrazolo [1,5-a] pyrimidine and pyrazolo [5,1-c][1,2,4] triazin derivatives

4-Phenyl-2H-pyrazol-3ylamine 3 has been prepared by reaction of 2-phenyl-3-piperidine-1-yl-acrylonitrile [6] with hydrazine hydrate under microwave irradiation. Compound 3 reacted with acetylacetone and ethyl acetoacetate to yield pyrazolopyrimidine derivatives 7 and 8, respectively. Pyrazolopyrimidine derivative II can be formed by reaction of 3 with 2-ethoxymethylene-malononitrile. Compound 3 can be diazotized to yield the diazonium chloride and coupled with 6 to yield pyrazolotriazine derivative 25. Structures of the synthesized compounds were confirmed by their IR and NMR spectroscopic data

Microwave mediated facile synthesis of some novel pyridine, pyrimidine, pyrazole, pyrazolo [1,5-a] pyrimidine and triazolo[1,5-a]pyrimidine pendant to pyrrole

The synthetic potency of E-3-[dimethylamino]-1-[1H-pyrrol-2-yl]prop-2-en-1-one towards some nitrogen nucleophiles was investigated under microwave irradiations as a convenient route for the synthesis of some novel pyridine, pyrimidine, pyrazole, pyrazolo [1,5-a] pyrimidine and Triazolo[1,5-a] pyrimidine derivatives

Synthesis of certain pyrazolol [3,4-d] pyrimidine derivatives of potential anti-inflammatory activity

The synthesis of twenty nine novel derivatives of pyrazolol [3,4-d] pyrimidines as non acidic nonsteroidal anti-inflammatory drugs has been achieved via reaction of 4-chloro-l-phenylpyrazolo [3,4-d] pyrimidine with different substituents including 4-amino-3-methylphenol, 4-phenylene diamine and 4-acetamidophenol. The anti-inflammatory activity of thirteen representative compounds have been screened compared to indomethacin as a reference drug. The results revealed that all the tested compounds showed anti-inflammatory activity with the exception of 10a.

In vitro antioxidant activity and scavenging effects of some new 1,3,5-triphenyl-2-pyrazolines and 3-[2"-hydroxy naphthalen-1"-YL]-1, 5-diphenyl-2-pyrazolines

A new class of potential pyrazoline derivatives had been synthesized and evaluated for their anti oxidant activities. The obtained five new 1,3,5-triphenyl-2-pyrazolines and another ten 3-[2"-hydroxynapthalen- 1"-yl]-1,5-diphenyl-2-pyrazolines were evaluated for antioxidative activities by using different reactive oxygen species [ROS] assays containing superoxide anion, hydroxyl radical, ABTS cation radical scavenging assays and inhibition of lipid peroxidation assay. The compounds exhibited more prominent effects in scavenging the free radical assays and also inhibited the lipid peroxidation. Compounds 10,13 possessing trimethoxy substitution on phenyl ring at position 5 of the 2-pyrazolines exhibited maximum activity, infact more than that of the standard drug ascorbic acid. Compounds11, 3, 4, 2 and 1 having dimethyl amino groups at position 4 of the phenyl ring at position 5 of the 2-pyrazolines also showed good activity. The present study revealed that an electron releasing group at position 4 of the phenyl ring is very much essential for all these 2-pyrazolines to show significant activity

Conveninent synthesis and antimicrobial activity of pyrazolo [3,4-d] pyrimidine derivatives

Pyrazole derivatives 3a,b were formed upon reacting phenylhydrazine with ketene S, S-acetal or tetracyanoethylene. The pyrazole derivatives 3a, b were in turn used as precursors for the preparation of pyrazolo [3,4-d] pyrimidines which are expected to possess considerable chemical and pharmacological activities. The antimicrobial activity of the prepared compounds was tested

Synthesis of new pyridine, pyrazole and pyrimidine derivatives of potential antimicrobial effect

Reaction of 2- acetyl tetralin [1] with some aldehydes was conducted in presence of malononitrile and/or ethylcyanoacetate and ammonium acetate, yielded tetrahydronaphthalenyl nicotinonitrile of types 2 and 3. Condensation of 1 with aromatic aldehydes afforded the respective chalcones 4a, b, which yielded pyrazolines 5a, b, phenyl pyrazolines 6a, b, 2-pyrimidinones 7a, b and 2-thiopyrimidines 8a, b upon reaction with hydrazine, phenyl hydrazine, urea, and thiourea, respectively. Some of the synthesized compounds have been screened for their antimicrobial activity against various strains of bacteria and fungi

Activated nitriles in heterocyclic synthesis: synthesis of substituted pyrazolopyridine, pyridine, 4H-pyran and naphthodiapyran derivatives

Several new pyrazolopyridines VIa-c were synthesized by reacting 4-nitrosoantipyrine [IIa] with arylidenemalononitriles Ia-c or ethyl arylidenecyanoacetates If-h. Reaction of Ia-c with 4-[azidomethylcarbonyl] antipyrine [IIb] afforded the pyridine derivatives XVI. The 4H-pyrans and naphthodipyran derivatives XVIII- XXI were prepared by reacting I with polyhydric phenols

Synthesis of some new isoxazolidin-3,5-diones, pyrazolidin-3,5-diones and barbituric acids of expected antimicrobial activity

New isoxazolidin-3,5-diones[3,8], pyrazolidin-3,5-diones[4a,b,9] and other related products of barbituric acid 5a, 10 and thiobarbituric acids 5b were synthesized using the malonic acid diethyl ester 2 and 7 as intermediates. The evaluation of the antimicrobial activity of these newly compounds was carried out. The results of the study were given

Reactions with hydrazonoyl halides, XVIII: synthesis of pyrolidino [3,4-c] pyrazole, pyrazolo [3,4-d] pyridazine, imidazo [1,2-a] pyrimidine, pyrasolo [3,4-d] pyrimidine and other heterocyclic derivatives

A synthesis of 1,4-benzothiazine, 1,4-benzoxazine, 1,4-quinoxaline, imidazo[1,2-a] pyridine, imidazol [1,2-a] pyrimidine and pyrazole derivatives was accomplished from the reaction of hydrazonoyl bromide I with 2-aminothiophenol, 2-aminophenol, 1,2-phenylenediamine, 2- aminopyridine, 2-aminopyrimidine and some active methylene. Also, compound 1 reacted with some dipolorophile to give pyrazolines and pyrrolidino [3,4-c] pyrazolines. All structures were elucidated on the basis of elemental analyses and spectral data

Synthesis of some new pyrazolones as potent anti-inflammatory agents

A series of 1,2-diphenyl-3,5-bis [alkyl and /or aryl amino] pyrazolium perchlorates [2a-e] 1,2-diphenyl-3-substituted 5-pyrazolones 3a-c, 4a-c, 6 and 1,2 diphenyl-5-pyrazolone Schiff's bases 7a-d were prepared. Some of the prepared compounds were tested for their antiinflammatory, analgesic, and antipyretic activities

Studies on dehydro-l-ascorbic acid 2-arylhydrazones: conversion into substituted triazoles and pyrazolinediones

The 2-p-chlorophenylhydrazone of dehydro-L-ascorbic acid was reacted with hydroxyamine giving the 3-oxime. Dehydrative cyclization of the latter gave the triazole derivative. The lactone ring cleaved upon treatment with hydrazine, methylamine or dimethylamine giving the corresponding triazole carboxamide derivative. Periodate oxidation of the triazole carboxamide gave the 3-formyltriazole which upon reduction gave the corresponding alcohol, characterized as its monoacetate. The 2-hydrazone was condensed with arylhydrazine giving the mixed bis- hydrazones, which underwent rearrangement to the pyrazolinediones and gave the bicyclic 3,6-anhydro derivatives upon treatment with cupric chloride

Studies on dehydaro-d-erythro-and l-threo-ascorbic acid 2-arylhydrazone-3-oximes and mixed bishydrazones: conversion into substituted triazoles and pyrazolinediones

Reaction of p-nitrophenyltriazole of dehydro-D-erythro-ascorbic acid [I] with hydrazine hydrate in MeOH yielded the corresponding triazole hydrazide [II] which gave the triacetyl derivative [III]. Periodate oxidation of [II] gave the 3-formyltriazole derivative [IV] which formed a triacetyl derivative [VI]. The 3-formyl derivative [IV] was condensed with hydrazine hydrate and O-phenylenediamine to give compounds [VII] and [VIII], respectively. Treatment of [I] with ammonium hydroxide solution and MeOH gave the triazole carboxamide [IX] which produced two different acetyl derivatives [X] and [XI]. The p-nitrophenylhydrazone zone of dehydro-D-erythro-[XII] and dehydro-L- threo-ascorbic acid [XIII], reacted with phenylhydrazine to give the mixed bisarylhydrazones [XIV] and [XV], respectively, which formed the diacetyl derivatives [XVI] and [XVII]. Compound [XIV] underwent rearrangement to the corresponding pyrazole derivative [XVIII] which gave the acetyl product [XIX]. Periodate oxidation of [XVIII] gave the 3-formylpyrazole [XX] which yielded different condensation products [XXI]-[XXV]. Cupric chloride oxidation of [XV] gave the 3,6-anhydro derivative [XXVI] which characterized as its monoacetyl derivative [XXVII]

Studies on dehydro-l-ascorbic acid 2-nitrophenyl-hydrazone: conversion into pyrazolinedione and thiadiazoline derivatives

The p-nitrophenylhydrazone of dehydro-L-ascorbic acid [I] reacted with methylhydrazine in MeOH giving the pyrazolinedione [V] and not the expected mixed bishydrazone [III]. The pyrazole derivative gave the tri-O-acetyl and tri-O-benzoyl derivatives [VI] and [VII], respectively. Periodate oxidation of [V] gave the 3-arboxaldehyde derivative [VIII] which was reduced by NaBH4 to the corresponding alcohol [IX] which formed the monoacetyl derivative [X]. The 3-carboxaldehyde condensed with hydroxylamine to give the 3-hydroxyiminomethyl derivative [XI], which upon acetylation gave the 3-acetoxyiminomethyl derivative [XII]. Similarly, benzoylation of [XI] gave the 3-benzoyl derivative [XIII]. The 3-thiosemicarbazone [XIV] of [VIII] gave the bicyclic derivative [XV] upon treatment with benzoyl chloride in pyridine. Treatment of [XV] with hydrazine hydrate gave [XVII]. which upon benzoylation gave [XVIII]