M. A. Metwally

Synthesis and antimicrobial activity of some new thiazole, thiophene and pyrazole derivatives containing benzothiazole moiety.

In an attempt to find a new class of antimicrobial agents, a series of thiazole, thiophene, pyrazole and other related products containing benzothiazole moiety were prepared via the reaction of N-(benzothiazol-2-yl)-2-cyanoacetamide (1) with appropriate chemical reagents. These compounds were screened for their antibacterial activity against gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes), gram-negative bacteria (Pseudomonas phaseolicola and Pseudomonas fluorescens) and antifungal activity against Fusarium oxysporum and Aspergillus fumigatus. Among the synthesized compounds, thiophene 13 showed equal activity with chloroamphenicol against S. aureus (MIC 3.125 microg/mL), while its activity was 50% lower than of chloroamphenicol against S. pyogenes. Thiazole 3 and pyrazolo[1,5-a]pyrimidine 21 b were found to exhibit the most potent in vitro antifungal activity with MICs (6.25 microg/mL) against A. fumigatus and F. oxysporum. Structures of the newly synthesized compounds were established by elemental analysis and spectral data.

Enaminonitrile in heterocyclic synthesis: Synthesis and antimicrobial evaluation of some new pyrazole, isoxazole and pyrimidine derivatives incorporating a benzothiazole moiety

Enaminonitrile 2 was used as key intermediate for the synthesis of polyfunctionally substituted heterocycles (e.g. pyrazoles, isoxazole, pyrimidines, thiazolo[3,2-a]pyrimidine, tetrazolo[1,5-a]pyrimidine, pyrido[1,2-a]pyrimidine, 1,5-benzodiazepine, and pyrazolo[1,5-a]pyrimidine) incorporating benzothiazole moiety via its reactions with some N-nucleophiles. The newly synthesized compounds were characterized by IR, (1)H NMR and mass spectral studies. Representative compounds of the synthesized products were tested and evaluated as antimicrobial agents.

Synthesis of new 5-thiazolyl azo-disperse dyes for dyeing polyester fabrics

Diazotized aryl amines were coupled with 2-aminothiazoles 1 and 2 to give the corresponding thiazolylazo dyes 3 and 4, respectively. 2-Amino-5-arylazothiazoles 5 reacted with chloroacetyl chloride to afford the chloro-acetamide derivatives 6 which further reacted with 2-mercaptobenzothiazole to furnish a new series of 5-arylazothiazolyl dyes 7. The azo structure of the dyes (rather than the tautomeric hydrazo structure) was assessed by ab initio DFT calculations at the B3LYP/6-31G* level. These dyes were applied to polyester fabric as disperse dyes and their fastness properties were evaluated.

Synthesis of some new thiazole derivatives of pharmaceutical interest

Condensation of 1,3-thiazolidinone derivatives 1a-c with different aromatic aldehydes and/or aryldiazonium chlorides gave the corresponding arylidenes 2-10 and arylazo-1,3-thiazolidinones 12-20. Bromination of 12 resulted in the formation of dibromo derivative 21. Treatment of 1a-c with HCHO-piperidine gave the Mannich adduct 24. Compound 1a was hydroxymethylated, oxidized and formylated to yield the products 25-28. The structures of the new products were confirmed by spectral and analytical methods.

Recent trends in the chemistry of 2-aminobenzothiazoles

The chemistry of 2-aminobenzothiazoles has gained increased interest in both synthetic organic chemistry and biological fields, since a large number of developments in the use of such compounds, covering the literature up to 2007, seem to be of considerable value. The present review presents their synthetic methods and chemical reactions. The reactions are subdivided in groups that cover reactions at the amino substituent without touching the benzene ring and reactions which involve both nitrogen in the formal amidine system to give fused heterocyclic systems. Most imaginable reaction types have been successfully applied and used, as many of the synthesized compounds exhibit interesting biological activity in various fields.

Synthesis, antitumor, cytotoxic and antioxidant evaluation of some new pyrazolotriazines attached to antipyrine moiety

Iminopropanehydrazonoyl cyanide 4 was achieved upon reaction of antipyrine diazonium salt 2 with 3-iminobutanenitrile (3) in EtOH/AcONa. 3-Aminopyrazole derivative 5 was obtained upon reaction of 4 with hydrazine hydrate. Diazodization of 5 afforded the diazonium salt 6 which coupled with active methylene compounds 7-10, 19, 20, 25, 29 and 32 in pyridine to give aryl hydrazone derivatives 11-14, 21, 22, 26, 30 and 33, respectively. Refluxing of compounds 11-14, 21, 22, 26 and 33 in acetic acid afforded the pyrazolotriazines 15-18, 23, 24, 28 and 35, respectively. The newly synthesized compounds were screened for their cytotoxic and antioxidant activities. The results showed clearly that compounds 4, 5, 13, 22, and 24 displayed promising in vitro anticancer activity against four different cell lines (HepG2, WI 38, VERO and MCF-7). Compounds 4 and 22 are the more potent antioxidant and anticancer agents. On the other hand, most of the compounds exhibited good cytotoxic activity toward (EAC).

3-Acetylindoles: Synthesis, Reactions and Biological Activities

This review deals with synthesis and reactions of 3-acetylindoles as well as their biological activities. The data published over the last few years on the methods of synthesis and chemical properties of 3-acetylindoles are reviewed here for the first time. 3-Acetylindole derivatives have been in the centre of at- tention of researchers over many years due to the high prac- tical value of these compounds, in the first place, the unusu- ally broad spectrum of biological activities. For example, 4- (1H-indol-3-yl)-2-hydroxy-4-oxobut-2-enoic acid was useful as anti-HIV agent, other compounds derived from 3-acetylindoles used in the treatment of gastrointestinal, car- diovascular and CNS disorders, and also used as HIV-1 inte- grase inhibitors. Despite this importance, 3-acetylindoles have not been previously reviewed. The main purpose of this review is to present a survey of the literature on 3- acetylindoles chemistry and provides useful and up-to-date data for medicinal chemists.

Versatile 2-amino-4-substituted-1,3-thiazoles: synthesis and reactions

Syntheses and reactions of 2-amino-4-substituted-1,3-thiazoles are reviewed in a formal way. The title compounds are most easily accessible by various approaches, and even waste-free solid-state procedures have been developed. The substitution in 4-position has synthetic reasons and therefore most interest accumulates around these derivatives of 2-aminothiazole. The high reactivity of both the amino group and the positions 3 and 5 of the 1,3-thiazole ring are used for numerous syntheses in a comprehensive way. The reactions are subdivided in groups that cover reactions at the amino substituent without touching the thiazole ring, reactions which involve both nitrogens in the formal amidine system to give thiazolo-pyrimidinones and -imidazoles as well as more involved polycondensed N,S-heterocycles with multiple possibilities for substituents, and substitution reactions at the 5-position of the thiazole ring. Most of the imaginable reaction types have been successfully applied and used, as many of the synthesized compounds exhibit interesting biological activity in various fields.

Utility of isothiocyanates in heterocyclic synthesis

Reaction of substituted pyrazolin-5-one and 3-phenyl-5-isoxazolone 1a-c with phenyl isothiocyanate in basic DMF gave the non-isolable sodium salt of the adduct 2a-c which was treated with HCl to give the corresponding thiocarbamoyl derivatives 3a-c . The latter compounds underwent heterocyclization upon treatment with chloroacetyl chloride and ethyl bromoacetate to give the corresponding thiazolidinone derivatives 6 and 7 . Compound 3a,b was oxidized to yield benzothiazoly pyrazolinone derivatives 8a,b . Also, nucleophilic substitution of 2 and 3 and with different nucleophilic reagents afforded the products 9-14 . Cyclocondensation of the thiocarbamoyl salt with some halogenated esters or acid chloride derivatives such as f -bromopropionate, ethyl chloroformate and f -bromo diethyl malonate afforded cyclized polyfunctionally thiazinone, thiazetidinone and thiazolidinone derivatives respectively 15-17 . The structures of the products were confirmed by spectral and micro analytical data.

2-Acetylbenzofurans: synthesis, reactions and applications

This review deals with synthesis and reactions of 2-acetylbenzofurans. Some of these reactions have been applied successfully to the synthesis of biologically important compounds. The main purpose of this review is to present a survey of the literature on 2-acetylbenzofurans chemistry and provides useful and up-to-date data for their applications since such compounds have not been previ- ously reviewed.