Synthesis of Some Triazolophthalazine Derivatives for Their Anti-Inflammatory and Antimicrobial Activities

• Published in: Archiv der Pharmazie (Weinheim) 2011-08, Vol.344 (8), p.530-542
• Main Authors: Habib, Nargues S., Farghaly, Ahmed M., Ashour, Fawzia A., Bekhit, Adnan A., Abd El Razik, Heba A., Abd El Azeim, Tarek
• Format: Article
• Language: English
• Subjects: Acute toxicity; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - toxicity; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - toxicity; Anti-inflammatory/antimicrobial activities; Antimicrobial agents; Drug Design; Drug Discovery; Microbial Sensitivity Tests; Phthalazines - chemical synthesis; Phthalazines - pharmacology; Phthalazines - toxicity; Structure-Activity Relationship; Triazoles - chemical synthesis; Triazoles - pharmacology; Triazoles - toxicity; Triazolophthalazines; Ulcerogenic effect
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201100053

Several novel series of triazolophthalazine derivatives namely; pyrazolylethenyltriazolophthalazinones (4a–d), styryltriazolophthalazinones (5a,b), aryloxopropenyltriazolophthalazinones (7a,b), pyrazolinyl‐ (8a,b), (9a,b) and (10a–f), pyrazolyl‐ (11a–d), (1,2‐oxazol‐5‐yl)‐1,2,4‐triazolo[3,4‐a]phthalazin‐6(5H)‐ones (14a,b), triazolo[3,4‐a]phthalazin‐3‐yl‐pyridine‐3‐carbonitriles (12a,b), triazolo[3,4‐a]phthalazin‐3‐yl)ethylthioacetic acids (13a,b) and 2‐aryl‐5‐arylamino‐1H,5H‐pyrazolo[2″,3″‐1′,5′]imidazo[3′,4′‐1,5]‐1,2,4‐triazolo[3,4‐a]phthalazin‐12(13H)‐ones (15a–c) have been synthesized. The anti‐inflammatory activity of representative compounds has been studied. Compounds 8b, 10c, 10f, 11b, 12a, 13b, and 15a showed anti‐inflammatory activities comparable to that of the reference standard, indomethacin. They exhibit also minimal ulcerogenic effect relevant to the reference standard and were found to be non‐toxic up to 120 mg/kg orally or up to 75 mg/kg through parenteral route. Concerning the antimicrobial activity; compounds 12b and 13b were found to be equipotent to ampicillin against Staphylococcus aureus, while compounds 10a and 10f were found to be as potent as ampicillin against E. coli, whereas compound 14b exhibited equipotency to clotrimazole against Candida albicans. Compounds 8b, 10f, 11b, 12a, and 13b exhibited, besides their antimicrobial activity, moderate to potent anti‐inflammatory profiles. This represents a fruitful matrix for the development of a new class of dual non‐acidic anti‐inflammatory/antimicrobial agents. Several novel series of triazolophthalazine derivatives has been synthesized. The results reveal that compounds 8b, 10c, 10f, 11b, 12a, 13b, and 15a showed anti‐inflammatory activities comparable to indomethacin. Compounds 8b, 10f, 11b, 12a, and 13b exhibited, besides their antimicrobial activity, moderate to potent anti‐inflammatory profiles.