RESUMO
5-Deazaflavins and their homologues have been known as potential riboflavin antagonists, bioreductives, and compounds with potent antitumor activity. 2-Amino-4-methylquinoline-3-carbonitrile (2) was prepared as unreported starting material for several interesting 2-deoxo-5-deazalloxazine derivatives. Cyclization of 2 using formamide afforded the 2,4-deoxo-5-deazaalloxazine derivative 7, which was subjected to deamination with nitrous acid to give the 2-deoxo-5-deazaalloxazine (8). The compound 8 was also obtained via 13 by treating the latter with refluxing formic acid or formamide and used as a precursor for synthesis of several 2-deoxo-5-deazaalloxazines 18, 19, 20, 21 and 22. The pharmacological and biological properties of these compounds are still under investigation.
Assuntos
Flavinas/síntese química , Pteridinas/síntese química , Pirimidinonas/síntese química , Antineoplásicos/síntese química , Antineoplásicos/química , Antivirais/síntese química , Antivirais/química , Flavinas/química , Pteridinas/química , Pirimidinonas/química , Riboflavina/antagonistas & inibidores , Análise EspectralRESUMO
A series of 2-(3-Arylpropenoyl)benzimidazole, 3a-d, and their corresponding N1-methyl analogues, 3e-h, were synthesized from p-substituted benzaldehyde and 2-acetylbenzimidazole or 2-acetyl-1-methylbenzimidazole, respectively. The in vitro alkylating activities of these alpha-beta-unsaturated ketones were investigated using L-cysteine as a model of cellular thioles at pH 7.4 and 37 degrees C. No significant difference between the alkylating activities of 3a-d and 3e-h as expressed from the pseudo first-order rate constants of the reactions of these derivatives with L-cysteine monitored by HPLC. However, significant variations in the rates of alkylation among these derivatives relative to the p-substituted group on the aryl moiety were observed, which is attributable to the electronic parameters of the substituted groups. The in vitro cytotoxic activity provided that the p-nitro derivative; 3d has some selectivity for cell lines of leukemia, renal cancer and breast cancer. The compounds were completely inactive as anti-HIV agents. Molecular modeling for all derivatives was undertaken.
Assuntos
Fármacos Anti-HIV/síntese química , Antineoplásicos Alquilantes/síntese química , Benzimidazóis/síntese química , Chalcona/síntese química , Fármacos Anti-HIV/farmacologia , Antineoplásicos Alquilantes/farmacologia , Benzimidazóis/farmacologia , Chalcona/farmacologia , Cromatografia Líquida de Alta Pressão , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Metilação , Modelos Moleculares , Células Tumorais CultivadasRESUMO
The key compound 1-amino-8-iminocyclopenta[b]thieno[2,3-d]pyrimidine (5g) was prepared by reaction of 2-amino-3-cyano cyclopenta[b]thiophene (1) with triethyl orthoformate followed by cyclization with hydrazine hydrate in ethanol. Refluxing of 1 with triethyl orthoformate in the presence of acetic anhydride gave an unexpected product 2. while reaction with aromatic amines gave the condensation products 4a-c. Reaction of 5g with formic acid, other formate derivatives, ethoxymethylenemalononitrile and ethyl ethoxymethylenecyanoacetate gave the same product cyclopentathieno-[2,3-d]-1,2,4-triazolo[3,2-f]pyrimidine 6. Compound 7 was prepared by different methods. Treatment of 5g with dicarbonyl compounds gave the triazol derivatives 8-11. Reaction of 5g with phenyl isothiocyanate, carbon disulphide and ethyl chloroformate gave the corresponding derivatives 12-14, respectively. Condensation of 5g with some selected aromatic and heterocyclic aldehydes, acetone, N-acetyl isatin and isatin gave the condensation products 15a-e, 16-18, respectively in good yields. Many of the synthesized compounds were tested in vitro for their inhibitory activity against a variety of bacteria such as: Serratia rhodnii, Bacillus cereus, Staphylococcus citreus and Pseudomonas aeruginosa and fungi such as: Aspergillus flavus, Penicillium chrysogenum and Alternaria alternarta. Some compounds showed modest activity.
Assuntos
Anti-Infecciosos/síntese química , Antifúngicos/síntese química , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Pirimidinas/síntese química , Antibacterianos , Anti-Infecciosos/farmacologia , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana , Pirimidinas/farmacologiaRESUMO
The named compound was reacted with thiosemicarbazide and/or semicarbazide to produce the corresponding condensation products II and V respectively. Reaction of II with chloroacetic acid in ethanol containing anhydrous sodium acetate yielded III. Condensation of III with aromatic aldehydes yielded the corresponding arylidene derivatives (IV). Oxidation of the semicarbazone V with selenium dioxide gave 2-(1,2,3-selenadiazole-4-yl)benzimidazole (VIa, b) while with thionyl chloride it gave 2-(1,2,3-thiadiazole-4-yl)benzimidazole (VIIa, b). The chalcones of 2-acetyl and/or 1-methyl-2-acetylbenzimidazole were condensed with hydrazine hydrate, phenylhydrazine and/or hydroxylamine to produce 2-(5-aryl-1(H)-pyrazolin-3-yl)-, 2-(5-aryl-1-phenyl-2-pyrazolin-3-yl)- and 2-(5-aryl-2-isoxazolin-3-yl)benzimidazole (IX, X, XI) respectively.