Synthesis and antiulcer activity of novel 5-(2-ethenyl substituted)-3(2H)-furanones

Abstract

In order to investigate new antiulcer agents, spizofurone 1 (AG-629) was fragmented and reassembled to generate 5-phenyl-2,2-dimethyl-3(2H)-furanone (bullatenone, 2). Because of the antiulcer activity of 2,5-phenyl-substituted 2,2-dimethyl-3(2H)-furanones (3-6) were made and shown to have poor activity. Insertion of an ethenyl link between the furanone and phenyl rings gave 5-(2-phenylethenyl)-2,2-dimethyl-3(2H)- furanone (7). This compound had better activity than 2. Compounds 8-41 were synthesized to evaluate the SAR in 5-(2-ethenyl substituted)-3(2H)-furanones. Electron-withdrawing substituents on the aromatic ring (8, 10, 19, and 20) gave 2-3-fold higher activity. Further increases in the activity were found when the phenyl ring was replaced by heterocyclic nuclei. Compounds that contained a thiophene (29), pyridine (24-26), or quinoline ring (32) had the best activity. Replacement of the methyl group on the furanone ring with a phenyl (34) or p-fluorophenyl (40) substituent in the 2-pyridine series gave compounds with activity that ranked with the best obtained in this study. The best compounds from the above SAR studies were evaluated in the ethanol-necrosis model for duration of cytoprotection action. Compounds 19, 24, and 29, which had the best duration of action, were tested with AG-629 in the acidified aspirin and indomethacin-induced lesion models. Only compound 24 had equivalent activity with AG-629 in both models.

5-(Biphenyl-4-yl)-3-(3-methoxybenzylidene)furan-2(3H)-one

“…For potential anti-ulcer agents containing a furanone structure, see: Felman et al (1992). For the role of furanones in the biochemical processes of the human body, see: Rappai et al (2009).…”

Synthesis of Heterocyclic Systems by Transition‐Metal‐Catalyzed Cyclization‐Migration Reactions – A Diversity‐Oriented Strategy for the Construction of Spirocyclic 3(2H)‐Furanones and 3‐Pyrrolones

“…Moreover, pharmaceutical activity, such as inhibitory activity on COX-2, [35] cytotoxic activity against tumor cells, [36] and inhibitory activity on MAO, [37] has been reported for several substances containing the 3(2H)-furanone moiety. [38] The construction of 3(2H)-furanones typically relies on classical condensation methods such as the acid-catalyzed cyclocondensation of substituted αЈ-hydroxy 1,3-diketones, whereas the bond formation between C5 and O1 is used in a cyclization step with the substitution pattern and the hydroxy group at C2 being installed at an earlier stage. [39,40] An alternative strategy involves unsaturated frameworks as starting materials for transition-metal-catalyzed 5-endo heterocyclizations.…”

Synthesis, Characterization and Antibacterial Evaluation of Some Azole Derivatives

“…[12][13] Isoxazole ring system occupies prime position in the design and synthesis of novel therapeutic agents. In addition to this, they are known to possess antiepileptic, 14 anticancer, 15 antimicrobial, [16][17] immunomodulatory, 18 antinociceptive, 19 anti-inflammatory, 20 antiplatelet, 21 antiulcer 22 activities and even more. During the last decade, most bacterial pathogens have exhibited antimicrobial resistance, and considerable effort has been directed at developing new agents to replace those whose usefulness has been eroded by resistance.…”