El-Sayed A. M. Badawey

Nonsteroidal antiinflammatory agents - Part 1: Antiinflammatory, analgesic and antipyretic activity of some new 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-ones

Abstract In our reinvestigation of the cyclocondensation reaction of aminoguanidine bicarbonate 1 with 2-acetylbutyrolactone 2 and ethyl cyclohexanone-2-carboxylate 6 , we have obtained the respective 1-amidino-3-pyrazolin-5-one derivative 3 and the 2-amidino-1,2,4,5,6,7-hexahydro-3 H -indazol-3-one 7 . These intermediates were utilized for the synthesis of two novel series of 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)-1,2,4,5,6,7-hexahydro-3 H -indazol-3-ones. Selected analogs from both series (15 compounds) were evaluated for their antiinflammatory activity in an acute and subacute model of inflammation. The analgesic and antipyretic activity of the target compounds were also evaluated. A structure-activity relationship (SAR) comparative study indicated that some compounds from both series exhibited excellent antiinflammatory activity, together with good analgesic and antipyretic activity and were found to be more potent than the reference drugs at a dose of 50 mg/kg, po. In consideration of the efficacy of the compounds in these assays, the 5-phenyl derivative 18 from the 1-(pyrimidin-2-yl)pyrazolinone series, the 5-butyl and 5-phenyl derivatives 26, 27 from the 2-(pyrimidin-2-yl)indazolone series were further studied at graded doses for their acute toxicity (ALD 50 ) and ulcerogenic activity and were shown to have a large safety margin (ALD 50 > 4.0 g/kg, po) and devoid of ulcerogenic potentialities when administered orally at a dose of 300 mg/kg.

Benzimidazole condensed ring system. IX. Potential antineoplastics. New synthesis of some pyrido[1,2-α]benzimidazoles and related derivative

Summary Some pyrido[1,2-a]benzimidazoles were prepared in order to investigate their in vitro antineoplastic and anti-HIV activities. Two compounds (9b, NSC 658526 and 15, NSC 664715) showed a variable degree of antineoplastic activity against some of the cell lines tested. Compound 9a (NSC 649900) exhibited a good in vitro antineoplastic activity with subpanel disease selectivity, particularly against most of the cell lines of leukemia and some cell lines from colon, melanoma and renal cancer panels.

Malonates in Cyclocondensation Reactions

The use of malonates such as diethyl malonates 9, (chlorocarbonyl)ketenes 15 and bis(2,4,6-trichlorophenyl) malonates 18 as reagents for cyclocondensation with 1,3-dinucleophiles to give six-membered heterocycles is described. Further attempts to use malonates such as bis(trimethylsilyl) malonates 19 and bis(carbamimidoyl) malonates 29 as new cyclocondensation agents are described .

Benzimidazole condensed ring systems. XI. Synthesis of some substituted cycloalkyl pyrido[1,2-a]benzimidazoles with anticipated antineoplastic activity

As part of a research project on the synthesis of a number of pyrido[1,2-a]benzimidazole derivatives with possible antineoplastic activity, and as a result of the interesting antineoplastic activity recorded for one such compound (NSC 649900), some new cycloalkylpyrido[1,2-a]benzimidazoles were prepared and evaluated for such activity. Compound (7c, NSC 682011) exhibited a good in vitro antineoplastic activity especially against most of the leukaemia cell lines. This compound has been selected by the NCI for further testing in a new in vivo anticancer hollow fibre assay.

Potential antineoplastics. Synthesis and cytotoxicity of certain 4-chloro-3-(2-chloroethyl)-2-methylquinolines and related derivatives

Summary In an extension of our work in the field of nitrogen heterocycles with potential cytotoxic activity, the synthesis of some substituted 4-chloro-3-(2-chloroethyl)-2-methylquinolines ( 10–13 ) from their parent 3-[1-(phenylamino)ethylioene]-dihybro-2(3H)-furanomes ( 6–9 ) is reported. The conversion of 10–13 to some thieno-, furo- and pyrrolo [3,2- c ]quinotines ( 14–27, 31–33 ) is also described. The compounds were evaluated for their toxicty in brine shrimp ( Artemia salina ), and their cytotoxicity against some clinically isolated human tumor in vitro. Several compounds exhibined good toxic activity against Artemia salina , which the furnace ( 6 , NSC 680781) displayed good antineoplastic activity and high selectivity against some cell lines from leukemia, lung cancer, colon and melanoma panels. This compound has been selected by the NCI for further testing in a new in vivo anticancer hollow fiber assay.

Potential anti-microbials. I. Synthesis and structure-activity studies of some new thiazolo[4,5-d]pyrimidine derivatives

Abstract The synthesis of several 2,3-dihydro-3,6-diaryl-5-mercapto-2-thioxothiazolo[4,5- d ]pyrimidin-7(6 H )-ones and related compounds are discussed. Some members of the series displayed broad in vitro anti-bacterial and anti-fungal activities. Three compounds were screened for anti-HIV potency but were inactive.

Potential anti-microbials. II. Synthesis and in vitro anti-microbial evaluation of some thiazolo[4,5-d]pyrimidines

Abstract Some thiazolo[4,5- d ]pyrimidines were prepared in order to investigate their antimicrobial activity. A significant inhibitory effect was recorded for many compounds against Staphylococcus aureus ATCC 25923 ( 3, 6, 9a ; MIC = 10–20 μg/ml), Escherichia coli ATCC 25922 ( 3, 5, 9b , MIC = 40 μg/ml) and Candida albicans DSM 70443 ( 6 , MIC = 50 μg/ml).

Benzimidazole condensed ring systems, III . Synthesis of some substituted 2,3-dihydrocyclopenta-1H-[4′,5′: 2,3]pyrido[1,2-a]benzimidazole-11-carbonitriles

SummaryThe synthesis of compound3 by condensing 1H-benzimidazole-2-acetonitrile (1) with ethyl cyclopentanone-2-carboxylate (2) in the presence of ammonium acetate is described. Methylation of3 with trimethyl phosphate yielded the N-methyl derivative4. Methods for converting3 to some of its related derivatives in which the carbonyl function was replaced by Cl, N3 and amines are also reported.ZusammenfassungDie Synthese der tetracyclischen Verbindung3 durch Kondensation von 1H-Benzimidazol-2-acetonitril (1) mit Cyclopentanon-2-carbonsäureester (2) in Gegenwart von Ammonacetat wird beschrieben. Die Methylierung von3 mit Trimethylphosphat liefert das N-Methylderivat4. Die Sauerstoffunktion in3 kann durch Chlor, Azid und Aminogruppen ersetzt werden.

Benzimidazole condensed ring systems, VI: Organic azides in heterocyclic synthesis, X: Synthesis of some substituted pyrimido[1,6-a]-benzimidazoles as potential antimicrobial agents

SummaryThe syntheses of 3-chloro derivatives of 2-alkyl-pyrimido[1,6-a]benzimidazol-1(2H)-ones2a, b as well as of 4,4-dichloro and 4,4-dibromo derivatives of 2-alkylpyrimido[1,6-a]benzimidazole-1,3(2H,4H)-diones3 a, b and4 are reported. Methods for converting some of the chloro compounds to azido (5, 6), amino (8), morpholino (9 a,10,11), piperidino (9 b), cyano (12), and methoxy (13) derivatives of the adopted tricyclic system are also described.ZusammenfassungDie Synthese von 3-Chlor-2-alkyl-pyrimido[1,6-a]benzimidazol-1(2H)-onen (2 a, b) und von 4,4-Dichlor- und 4,4-dibrom-pyrimido[1,6-a]benzimidazol-1,3(2H,4H)-dionen (3 a, b, 4) wird beschrieben. Diese Verbindungen lassen sich zu den entsprechenden Azido- (5, 6), Amino- (8), Morpholino- (9 a, 10, 11), Piperidino- (9 b), Cyano- (12) und Methoxy- (13) Derivaten umwandeln.

Condensed thiazoles, I: Synthesis of 5,7-disubstituted thiazolo[4,5-d]pyrimidines as possible anti-HIV, anticancer, and antimicrobial agents

SummaryA convenient and simple synthesis of 5-mercapto-3-phenyl-2-thioxo-2,3-dihydrothiazolo-[4,5-d]pyrimidin-7(6H-one(2) and its 5,7-dichloro (3), 5,7-diazido (4), 5,7-diamino (5), 5,7-dimerapto (6), 5,7-dimethylthio (7), and 6-methyl-5-methylthio (8) derivatives is described. The prepared compounds were screened for theirin vitro anti-HIV, anticancer, antibacterial and antifungal activities.ZusammenfassungDie Synthese von 5-Mercapto-3-phenyl-2-thioxo-2,3-dihydrothiazolo[4,5-d-pyrimidin-7(6H)-on (2) und seiner 5,7-dichloro-(3), 5,7-diazido-(4), 5,7-dimanio-(5), 5,7-dimercapto-(6), 5,7-dimethylthio- (7) und 6-methyl-5-methylthio-Derivaten (8) wird beschrieben. Die hergestellten Verbindungen wurden auf ihrein vitro anti-HIV, anticancerogenen, antibakteriellen und antimykotischen Aktivitäten geprüft.