Ahmed S. A. Youssef

Reactions of 5-Aroylmethylene-3-benzyl-4-oxo-2-thioxo-1,3- thiazolidines with Nitrile Oxides.

E,Z-5-Aroylmethylene-3-benzyl-4-oxo-2-thioxo-1,3-thiazolidines (3a-c) react with 4-methoxy and 4-chlorophenylnitrile oxides (4a and b) in pyridine solution to afford one or more of the following compounds: Z-3, Z-2,4-dioxo analogues 5 and 3,6-diaryl- 1,4,2,5-dioxadiazines (6a-b). The interconversion route is discussed and the structures of all of the synthesised compounds are proven by microanalytical and spectral data.

Design and Discovery of Novel Quinoxaline Derivatives as Dual DNA Intercalators and Topoisomerase II Inhibitors

Backgroun/Methods: In attempt to develop new potent anti-tumor agents, a series of quinoxaline derivatives was designed and synthesized. The novel compounds were tested in vitro for their anti-proliferative activities against HePG-2, MCF-7 and HCT-116 cell lines. Additionally, DNA binding affinities as well as DNA-top II inhibitory activities of the synthesized compounds were investigated as potential mechanism for anticancer activity. Compounds 13, 15, 16 and 19 exhibited good cytotoxicity activities against the three cell lines (IC50 ranging from 7.6 to 32.4 µM) comparable to that of doxorubicin (IC50 = 9.8 µM). RESULTS Interestingly, the results of DNA binding and DNA-top II inhibition assays were in agreement with those of the cytotoxicity tests, where the most potent anticancer compounds showed good DNA binding affinities (IC50 ranging from 25.1 to 32.4 µM) and DNA-top II inhibitory activities (IC50 ranging from 6.4 to 15.3 µM) comparable to those of doxorubicin (IC50 = 28.1 and 3.8 μM, respectively). Furthermore, molecular docking studies were carried out for the new compounds in order to investigate their binding pattern with the prospective target, DNA-top II complex (PDB-code: 3qx3).

Behaviour of some 2(3H)-furanones bearing a pyrazolyl group as alkylating agents

5-Aryl-3-(1,3-diphenylpyrazol-4-ylmethylene)-2(3H)-furanones (1a–c) were prepared by condensing 1,3-diphenyl-pyrazole-4-carboxaldehyde with 3-aroylpropionic acids in the presence of N,N-dimethyl(chlorosulfinyloxy)meth-animinium chloride as a cyclodehydrating agent. The reactions of these furanones with anhydrous aluminium chloride in benzene, toluene and anisole led to the formation of 4,4-diaryl-1-(1,3-diphenylpyrazol-4-yl)buta-1,3-diene-2-carboxylic acids (6) as mixtures of two geometrical (E,E- and E,Z-) stereoisomers. The unfavoured intramolecular alkylation of 1a–c compared with other furanones is discussed using Hyper Chem Professional (7) AM1 calculations.

The (E)/(Z)-ratio in the reaction of 5-(2-aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidines with bromine

Summary3-Aryl-, 3-benzyl-, and 3H-5-(2-aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidines3a–h react with bromine in acetic acid solution to give mixtures of the respective 5-aroylmethylene (E) and (Z) diastereomeric derivatives5 and6. They contain more than 85% of the (E)-diastereomers along with some pure isomers. The intermediacy of the 5-bromo derivatives4 is proven and a plausible route of the reaction is presented. Structures of compounds3–6 are evidenced by analytical and spectral data.Zusammenfassung3-Aryl-, 3-Benzyl- und 3H-5-(2-Aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidine3a–h reagieren mit Brom in essigsaurer Lösung zu Gemischen der entsprechenden diastereomeren 5-Arylmethylen-Derivate ((E) und (Z))5 und6. Sie enthalten mehr als 85% des (E)-Diastereomeren. Die intermediäre Natur der 5-Brom-Derivate4 wird bewiesen; ein Reaktionsweg wird vorgeschlagen. Die Strukturen der Verbindungen3–6 werden durch analytische und spektroskopische Daten abgesichert.

SYNTHESIS OF SOME BIOLOGICALLY ACTIVE HETEROCYCLES. REACTIONS OF THE HYDRAZIDE OF 2′-THIENOYL ANTHRANILIC ACID AND ITS 3,5-DIBROMO DERIVATIVE

Abstract The hydrazide of 2′-thienoyl anthranilic acid and its 3,5-dibromo derivative (1a and b) were condensed with carbon disulphide to give 1–3′-quinazolin-2-thione 5–2′′-aminophenyl-1,3,4-triazoles (2a, b). When treated with acetyl chloride 3-N-acetamidoquinazolin-4-ones (3a, b), with aromatic aldehydes the schiff bases 4 and 5(a, b). Potassium thiocyanate and phenyl isothiocyanate gave the semicarbazide derivatives (6a, b) while ammonium thiocyanate afforded the triazol-thiones (7a, b). Reaction with ethyl acetoacetate and acetylacetone gave the pyrazole derivatives 8 and 9 respectively; Biological activities of some of these compounds are tested.

Reactions of 3-substituted 5-Arylmethylene-1,3-Thiazolidin-2,4-diones with Azide and Cyanide Ions

3-substituted-5-arylmethylene-1,3-thiazolidine-2,4-diones 3a–e react- ed with sodium azide to afford pyrazolinone derivatives 8a–d as well as 5-(4-chlorophenylmethylene)-1,3 - thiazolidine-2,4-dione 7a in the case of 3d and 5-(4-methoxyphenylmethylene-1,3-thiazolidin-2,4-dione 7b as a sole product in the case of 3e . Reactions of potassium cyanide with 3b–d gave butyronitrile derivative 9 as well as 7a and a water soluble adduct that, upon treatment with chloroacetic acid, yielded 10 in the case of 3c and 3d . Also, the treatment of 3e with potassium cyanide afforded a mixture of 7b , but-3-enonitrile derivative 11 and 10 . Structures of all products were elucidated by microanalytical and spectral data.

REACTIONS OF 5-SUBSTITUTED-2-THIOXO-4-OXO-1,3-THIAZOLIDINES WITH 4-METHOXYPHENYLAZIDE

Abstract 4-Methoxyphenylazide cycloadds to the thiono function and undergoes nucleophilic attack at other electrophilic centers of 5-benzoylmethyl-(1a) and E,Z-5-(4-bromobenzoylmethylene)-(E,Z-2b) -2-thi-oxx-4-oxo-1,3-thiazolidines in non site selective reactions to afford variety of products. With la, the attack at the thiono as well as the hetero-ring carbonyl functions leads to the 5-benzoylmethylene-2-(4-methoxyphenylimino)-derivative (3) and the ring fission product 2–4. Similar treatment of E,Z-Zb gives a mixture of the respective E,Z-2-(4-methoxyphenylimino)-derivative (E,Z-5) containing 80% of the Z-configurated isomer (Z-5) and the ring enlarged thiazinonethione derivative (6), due to the attack at the thiono and exocyclic double bond functions, respectively. Rationalizations for the above mentioned conversions are given. Structures of all products are evidenced by microanalytical and spectral data.

Dodecanoyl thiosemicarbazide derivatives as useful synthons in the synthesis of 1,2,4-triazole, 1,3,4-thiadiazole, and 1,3-benzothiazole derivatives

ABSTRACT A convenient synthesis of the dodecanoyl thiosemicarbazide derivatives 3a, b has been achieved from the reaction of 2-benzamido-3-arylacryloylhydrazides 1a, b and lauroyl isothiocyanate (2). The thiosemicarbazide derivative 3a is used as precursor for synthesis of 1,2,4-triazole, 1,3,4-thiadiazole, and 1,3-benzothiazole derivatives. The antimicrobial activity of some of the synthesized compounds was tested. GRAPHICAL ABSTRACT

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

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).

Conversion of 5-Aryl-3-phenylthio-2(3H)-furanones into Some Nitrogen- and Sulphur-Containing Heterocycles

3-Phenylthio-5-aryl-2(3H)-furanones 4 were prepared from 2-phenylthio- 3-aroylpropionic acids 3 by a ring closure using acetic anhydride. Benzylamine reacted with 4 to give the benzylamide derivatives 5, which were cyclized to the corresponding 2(3H)-pyrrolones 6. The isothiazolone derivatives 7 were obtained from the benzylamides 5 by the action of SOCl2. A ring opening of furanone 4 with hydrazine hydrate gave the acid hydrazides 8. The latter hydrazides were utilized as starting materials for the synthesis of pyridazinone derivatives 9 and 11, 1,3,4-oxadiazoles 13, and triazolone derivatives 14.