Synthesis and antimicrobial activity of some new pyrimidinone and oxazinone derivatives fused with thiophene rings using 2-chloro-6-ethoxy-4-acetylpyridine as starting material

• Published in: Molecules (Basel, Switzerland) Switzerland), 2012-11, Vol.17 (11), p.13642-13655
• Main Authors: Hossan, Aisha S M, Abu-Melha, Hanaa M A, Al-Omar, Mohamed A, Amr, Abd El-Galil E
• Format: Article
• Language: English
• Subjects: Acids; acryloyl candidates; Analgesics; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antimicrobial agents; citrazinic acid; Fungi - drug effects; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Hydrolysis; Isonicotinic Acids - chemistry; Microbial Sensitivity Tests; Molecular weight; Oxazines - chemical synthesis; Oxazines - chemistry; Oxazines - pharmacology; oxazinone; Pharmacy; pyrimidinone; Pyrimidinones - chemical synthesis; Pyrimidinones - chemistry; Pyrimidinones - pharmacology; Sodium; Transition Temperature
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules171113642

A series of pyridines, pyrimidinones, oxazinones and their derivatives were synthesized as antimicrobial agents using citrazinic acid (2,6-dihydroxyisonicotinic acid) as a starting material. α,β-Unsaturated ketones 3a-c were condensed with cyanothio-acetamide in the presence of ammonium acetate to give 2-cyanopyridinethiones 4a-c, which were reacted with ethyl chloroacetate to yield the corresponding cyano esters 5a-c. The esters 5a-c were cyclized by action of sodium methoxide to aminoesters 6a-c, which were aminolyzed with ammonia to corresponding aminoamide derivatives 7a-c. Also, the esters 6a-c were hydrolyzed with NaOH to the corresponding sodium salt 8a-c, which were treated with acetic anhydride to afford 2-methyloxazinones 9a-c. The latter compounds were treated with ammonium acetate to afford 2-methylpyrimidinones 10a-c, followed by methylation with methyl iodide to yield 2,3-dimethyl-pyrimidinones 11a-c. The antimicrobial screening showed that many of these compounds have good antibacterial and antifungal activities comparable to streptomycin and fusidic acid used as reference drugs.