Synthesis,characterization and biological activity of some 1,2,4‐triazine derivatives

4‐Amino‐6‐methyl‐3‐(2H)‐thioxo‐5‐(4H)‐oxo‐1,2,4‐triazine ( 1 ) was condensed with 2‐methyl (or phenyl)‐4H‐3,1‐benzoxazin‐4‐one ( 5a,b ) in boiling acetic acid to give compounds 8‐11 . Reacting 1 with chloroacetyl chloride afforded the corresponding chloroacetamido and triazinothiadiazine derivatives 12 and 13 . Condensing 2 with succinic anhydride and/or phthalic anhydride yielded compounds 14 and 15 . Benzoylation of 4‐amino‐6‐methyl‐3‐(2H)‐thioxo‐5‐(4H)‐oxo‐2‐(2,3,4,5‐tetra‐O‐acetyl‐α‐D‐glucopyra‐nosyl)‐1,2,4‐triazine ( 19 ) afforded the corresponding 4‐N,N‐dibenzoyl derivative 20 . Deblocking of the N‐2 glycoside 21 and the S‐glycoside 22 by methanolic ammonia gave compounds 23 and 24 . Acetylation of 4‐amino glycoside 25a afforded the corresponding 4‐mono‐ and 4‐diacetyl derivatives 26 and 27 . Deamination of 25a,b yielded compounds 28a,b . Methylation of compound 28b afforded the corresponding N4‐ and S‐methyl derivatives 29 and 30 .     

Synthesis and biological evaluations of mono‐ and bis‐ferrocene uracil derivatives

Mono‐ ( 3a – 3e and 4a – 4e ) and bis‐ferrocene ( 5a – 5e and 6a – 6e ) conjugated 5‐substituted uracil derivatives that are bridged by 1,2,3‐triazole linker were synthesized. The impact of ferrocene unit and spacer between ferrocene and triazole on radical scavenging potency was observed. Bis‐ferrocenyl uracil derivatives exhibited better antiproliferative activities than their mono‐ferrocenyl analogs. Bis‐ferrocenyl methyl‐ ( 5b ) and halogen‐substituted ( 5e , 6c , and 6d ) uracil derivatives showed pronounced and selective cytostatic activities on colon adenocarcinoma (CaCo‐2) and Burkitt lymphoma (Raji) cells, with higher potency and selectivity than the reference drug 5‐fluorouracil. Generation of reactive oxygen species (ROS) in CaCo‐2 and Raji cells when treated with compounds 5b , 5e , and 6d was observed. Bis‐ferrocenyl 5‐chlorouracil 6c induced significant disruption in mitochondrial membrane potential that is accompanied by activation of apoptosis in CaCo‐2, Raji, and acute lymphoblastic leukemia (CCRF‐CEM) cells, while 6d caused mitochondrial dysfunction and apoptosis induction in CaCo‐2 and Raji cells. Potent antiproliferative activity of 6c and 6d could be associated with mitochondrial membrane potential disruption accompanied by apoptosis induction. Our findings highlighted 6c and 6d with potent and selective antiproliferative activity on CaCo‐2, Raji, and CCRF‐CEM cells that may be associated with targeting cancer cell mitochondria, as a molecular target.     

Synthesis and biological activity of some gossypol derivatives

Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 44–49, January–February, 1995. Original article submitted October 17, 1994.     

邻烷氧基羰基苯磺酰胺衍生物的合成、表征及生物活性

磺酰胺类化合物是继磺酰脲与咪唑啉酮除草剂之后开发的乙酰乳酸合成酶 (ＡＬＳ)抑制剂的另一重要领域 ,已筛选出一些高活性的新品种[1～ 3] 。为寻找新的性能优良的活性物质 ,进一步研究活性与结构的关系 ,本文设计将磺酰胺类和酰胺类除草剂的基本骨架用一个亚甲基 ＣＨ2 连结起来 ,相当于在磺酰脲桥链中间插入了一个亚甲基 ,共合成了 1 6个新的邻烷氧基羰基苯磺酰胺衍生物( 2ａ～ 2ｐ) ,并初步测试了它们的生物活性。1　实验部分1 1　仪器和试剂ＪＥＯＬＦＸ 90Ｑ型、ＢＲＵＫＥＲＡＣ Ｐ2 0 0型核磁共振仪 ,ＴＭＳ为内标 ;Ｓｈｉｍａｄ…     

Synthesis,characterization and biological activity of diorganotin dithioate derivatives

Reaction of dithioacid (ArCS₂CH₂CO₂H, Ar = phenyl, 2‐furyl or 2‐thienyl) with ⁿBu₂SnO gives monomeric (ArCS₂CH₂CO₂)₂Sn(Buⁿ)₂ in a 2:1 molar ratio, and dimeric {[(ArCS₂CH₂CO₂)Sn(Buⁿ)₂]₂O}₂ in a 1:1 molar ratio, respectively, which have been characterized by IR, NMR (¹H, ¹³C and ¹¹⁹Sn) spectra and elemental analyses. X‐ray crystal structure analyses indicate that the compound [(C₄H₃S)CS₂CH₂CO₂]₂Sn(Buⁿ)₂ is monomeric with the tin atom occupying a skew‐trapezoidal bipyramidal geometry. In addition, this compound forms a three‐dimensional structure through the weak intermolecular S^…S and Sn^…O interactions. Compound {[((C₄H₃S)CS₂CH₂CO₂)Sn(Buⁿ)₂]₂O}₂ is a centrosymmetric dimer with a cyclic Sn₂O₂ unit, in which the coordination modes of the two crystallographically unique carboxylic ligands are different. One acts as monodentate ligand by the carboxylate oxygen atom, the other bridges two tin atoms via only one carboxylate oxygen atom. Furthermore, each tin atom in this compound locates a distorted trigonal bipyramidal geometry. Biological activities of these organotin compounds show that they have hardly acaricidal activity, but display certain activities on fungi. In mononuclear tin compounds, the inhibition percentage of [(C₄H₃S)CS₂CH₂CO₂]₂Sn(Buⁿ)₂ in vitro for Alternaria solani and Physolospora piricola is 57.1% and 43.9%, respectively, while in dimers {[((C₄H₃O)CS₂CH₂CO₂)Sn(Buⁿ)₂]₂O}₂ shows high inhibition percentage for Gibbereila zeae (52.6%) and Physolospora piricola (50.0%), respectively. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis, characterization, and biological activities of some 3,5,6-trichloropyridine derivatives

Aromatic carboxylic acids on refluxing with 3,5,6-trichloro-2-pyridyloxyacetylhydrazide in POCl3 gave 5-aryl-2-(3,5,6-trichloro-2-pyridyloxymethyl)-1,3,4-oxadiazoles. The hydrazide on treatment with acid chlorides gave diacylhydrazines, whereas with arylsulfonyl chlorides acyl(arylsulfonyl)hydrazines were obtained. The latter two types of compounds were tested for their antibacterial and antifungal activities whereas 1,3,4-oxadiazole derivatives were tested for their herbicidal activity. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 711–717, May, 2006.     

Synthesis and biological activity of some new pyridazine derivatives

Summary Condensation of -aroyl--[1,3-diphenyl-5(4H)-oxo-pyrazol-4-yl] propionic acid with hydrazine hydrate affords 4,5-dihydro-3(2H)-pyridazinone (2). Reaction of2 with POCl₃ and P₂S₅ gives a dichloro derivative (7) and a dithione (4). The behavior of the dichloro and dithione derivatives toward various reagents was studied. Thein vitro antibacterial screening reveals moderate activities against certain bacteria.

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Synthese und biologische Aktivität einiger neuer Pyridazinderivate

Zusammenfassung Kondensation von -Aroyl--[1,3-diphenyl-5(4H)-oxo-pyrazol-4-yl]-propionsäure mit Hydrazinhydrat ergibt 4,5-Dihydro-3(2H)-pyridazinon (2). Reaktion von2 mit POCl₃ und P₂S₅ liefert ein Dichlorderivat (7) und ein Dithion (4). Das Verhalten dieser beiden Verbindungen gegenüber verschiedenen Reagentien wurde untersucht. Antibakterielles screening (in vitro) ergab mäßige Aktivität gegenüber verschiedenen Bakterienstämmen.

     

Synthesis,characterization, and biological activity of some lanthanide ternary complexes

Five complexes have been synthesized by the reaction of lanthanide(III) nitrate with 2-thenoyltrifluoroacetone (HTTA) and p-hydroxybenzoic acid (L). The complexes have been characterized by elemental analysis, molar conductivity, FT-IR, UV-Vis, ¹H NMR, TG-DTA, XPS, and transmission electron microscope. The general formula of the complexes is Na[Ln(TTA)₃L] (Ln?=?La³⁺,?Ce³⁺,?Nd³⁺,?Eu³⁺,?Er³⁺). The antibacterial activities indicate that all five complexes exhibit antibacterial ability against Escherichia coli and Staphylococcus aureus with broad antimicrobial spectrums. The antitumor activity of the five complexes against K562 tumor cell in vitro is measured using methyl thiazolyl tetrazolium (MTT) colorimetry. The results show that the complexes induce K562 tumor cell apoptosis, and the complexes exhibit inhibitory effect on leukemia K562 cells.     

Indole derivatives CI. Synthesis and biological activity of some tryptamines

The cyclization of hydrazones obtained by coupling of diazonium salts with ethyl-acetyl--phthalimidovalerate gives ethyl 5-substituted-3-(2-phthalimidoethyl)indole-2-carboxylates, the successive hydrolysis and decarboxylation of which make it possible to obtain 5-substituted tryptamines. The synthesized hydroxyethyl ester of serotonin was found to have pronounced antiradiation action.See [1] for communication C.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1496–1501, November, 1974.     

Synthesis,characterization, and biological activity of N′‐trifluoromethanesulfonyl‐2‐aminopyridine

The synthesis, characterization and biological activity of N′‐trifluoromethanesulfonyl‐2‐aminopyridine in connection with our studies of trifluoromethanesulfonyl derivatives of the pyridine ring have been achieved. In solution an equilibrium (∼ 50:50%) of the amide and imide tautomeric forms was observed, while in the solid state only the imide form was present. Biological tests on the compound showed no effect either upon the growth of Escherichia coli or on Staphylococcus aureus in the agar diffusion tests; however, the growth of Enterococcus faecalis was effectively inhibited. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:308–312, 2000     

Synthesis,structure, and biological activity of novel 4,5‐disubstituted thiazolyl urea derivatives

Novel 1‐(2,4‐dichlorophenyl)‐3‐[4‐aryl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐yl] urea derivatives were synthesized by the reaction of 2‐amino‐4‐sustituted phentyl‐5‐(1H‐1,2,4‐triazol‐1‐yl) thiazoles with 2,4‐dichloro‐1‐isocyanatobenzene. Structures of the title compounds were confirmed by the elemental analysis, ¹H NMR, and single crystal X‐ray diffraction analysis. Biological evaluation showed that some of them possess promising antitumor activities. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:2–6, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20375     

Synthesis,characterization, and in vitro biological studies of some novel pyran fused pyrimidone derivatives

A variety of pyrano[2,3‐d]pyrimidine‐5‐one derivatives 5 , 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 6 , 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j have been synthesized from 6‐amino‐4‐(substituted phenyl)‐5‐cyano‐3‐methyl‐1‐phenyl‐1,4‐dihydropyrano[2,3‐c]pyrazole derivatives 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j via cyclization using formic acid and acetic acid. All the newly synthesized compounds have been characterized by IR, ¹H NMR, ¹³C NMR, and elemental analysis. All the synthesized compounds have been screened for antibacterial, antifungal and antitubercular activity. J. Heterocyclic Chem., (2012).     

Synthesis,characterization and biological activity of bis(3‐Aryl‐1‐hexahydropyrimidinyl)methanes. Novel heterocyclic polyamine derivatives

A method is described for the synthesis of bis(3‐aryl‐1‐hexahydropyrimidinyl)methanes 1, by condensation of N‐aryl‐1,3‐propanediarnines 2 with formaldehyde. The reaction mechanism involves N‐arylhexahydropyrimidines 3 as intermediates. Such compounds can also be prepared efficiently by a methylene exchange reaction between bis‐hexahydropyrimidines 1 and the corresponding diamines 2. The antimicrobial activity of compounds 1 was evaluated by the disk diffusion method and some of them showed moderate to good growth inhibition activity.     

Synthesis,anti‐inflammatory,and anticancer activity evaluation of some heterocyclic amidine and bis‐amidine derivatives

Heterocyclic amidine derivatives of benzothiazole ( 6a , 6b , 6c ), benzimidazole ( 6d , 6e , 6f ), benzoxazole ( 6g , 6h , 6i ), and bis‐amidine derivatives of pyrimidine, ( 7a , 7b ) & triazole ( 7c , 7d , 7e ) ring system have been synthesized by nucleophilic addition reaction. All these compounds were screened for anti‐inflammatory and anticancer activities. At a dose of 50 mg/kg p.o., compounds 6c (39%), 6e (39%), and 6f (39%) exhibited anti‐inflammatory activity comparable to standard drug ibuprofen, which showed 39% activity and compounds 6b , 6e , 7a , and 7c exhibited moderate anticancer activity against cervix (HELA); neuroblastoma (IMR‐32); breast (MCF‐7), leukemia (THP‐1); and cervix (HELA) human cancer cell lines, respectively. J. Heterocyclic Chem., (2011).     

Synthesis and biological activity of some new aminoacylcarbazole derivatives. Part I

The syntheses of different 9-(N-phthalyl- or N-tosyl- or free aminoacyl)carbazoles and the corresponding derivatives of 3,6-dinitrocarbazoles and some derivatives of 3,6-diamino-9-(N-phthalylaminoacyl)carbazoles (II-XXXII) are described. Compounds VIII, XIII-XVII and XXIII-XXVII were found to be active against a number of microorganisms.     

Synthesis,characterization and in vitro antitumour activity of di‐ and tri‐organotin derivatives of fenbufen

The di‐ and tri‐organotin derivatives of fenbufen (4‐(4‐biphenyl)‐4‐oxobutyric acid), [{(n‐C₄H₉)₂Sn(OCOCH₂CH₂COC₆H₄C₆H₅‐4)}₂O]₂ ( 1 ) and R₃SnOCOCH₂CH₂COC₆H₄C₆H₅‐4 (R?C₆H₅, 2 ; c‐C₆H₁₁, 3 ; C₆H₅C(CH₃)₂CH₂, 4 ), have been prepared and characterized by means of elemental analysis, IR and NMR (¹H, ¹³C and ¹¹⁹Sn) spectroscopies. The crystal structure of 1 , bis[4‐(4‐biphenyl)‐4‐oxobutyrato]tetra‐n‐butyldistannoxane, has been determined and it is a centrosymmetric dimer with two distinct types of carboxylate moieties and tin atoms with distorted trigonal bipyramidal geometries. The in vitro antitumour activity of 1 and 2 against two human tumour cell lines was found to be higher than that for cis‐platin used clinically. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis, characterization and biological activity of polyketones

Polyketone resins have been prepared by the Friedel-Crafts polymerization of dithiophenylidenecyclopentanone (Ⅰ), dithiophenylidenecyclohexanone (Ⅱ) and dithiophenylideneacetone (Ⅲ) with adipoyl, sebacoyl and terephthaloyl dichlorides using boron trifluoride as catalyst and carbon disulphide as solvent. Polymers were characterized with IR, 1 H-NMR, and the results showed the presence of carbonyl of ketonic groups in the main chain. The polyketones have inherent viscosities of 0.40-0.70 dL/g. All the polymers are semicrystalline and most of them are partially soluble in most common organic solvents but freely soluble in aprotic solvents. The temperatures of 50% weight loss are as high as 185℃ to 280℃ in air, indicating that these aromatic polyketones have excellent thermal stability. All the polyketones were tested for their antimicrobial activity against bacteria and fungi.     

Synthesis,reactions, and biological study of some new thienopyrimidine derivatives as antimicrobial and anti‐inflammatory agents

Pyrimidine and thienopyrimidine derivatives play a very important role in organic chemistry because of their wide applications as bioactive compounds with multiple biological activities. However, a literature survey revealed that the merger of different groups in the thieno[2,3‐d]pyrimidine heterocyclic ring enhances its antibacterial, antifungal and anti‐inflammatory activities. This encouraged us to prepare a new series of thieno[2,3‐d]pyrimidine heterocyclic compounds and to test them as antimicrobial and anti‐inflammatory agents. These compounds have shown remarkable activity toward fungi, bacteria, and inflammation. Thus, these compounds have been prepared by the chloroacylation of 5‐amino‐4‐phenyl‐2‐(p‐tolylamino)thieno[2,3‐d] pyrimidine‐6‐carboxamide ( 4 ) using chloroacetyl chloride under neat condition to afford the target compound ( 6 ), which was used as precursor for the synthesis of a number of bioactive compounds. Thus reaction of the chloromethylpyrimidine derivative ( 6 ) with triphenylphosphine in dry benzene gave the corresponding ((4‐oxo‐9‐phenyl‐7‐(p‐tolylamino)‐3,4‐dihydropyrimido[4′,5′:4,5]thieno[2,3‐d]pyrimidin‐2‐yl)methyl) triphenylphosphonium chloride ( 7 ). Compounds 8a – 8c and 9a – 9c were obtained by the reaction of 7 with some selected aromatic aldehydes and ketones in methanol and sodium methoxide under Wittig reaction condition. The structures of the all new synthesized compounds were established on the basis of their analytical and spectral data (IR, ¹H NMR, ¹³C NMR, and MS).