Synthesis of Substituted Tri- and Tetracyclic Compounds Bearing a Pyridazine Core and their Biological Evaluation as Antimycobacterial Agents

• Published in: Archiv der Pharmazie (Weinheim) Vol. 333; no. 7; pp. 231 - 240
• Main Authors: Heinisch, Gottfried, Matuszczak, Barbara, Planitzer, Karin
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag GmbH 01-07-2000; WILEY‐VCH Verlag GmbH; Wiley-VCH
• Subjects: 1-b]pyridazino; 3-f; 4-b; 4]oxazepin-12(13H)-ones; 5]benzoxazepin-5(6H)-ones; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; antimycobacterial agents; antituberculotic agents; Biological and medical sciences; Medical sciences; naphtho; naphtho[2,1‐b]pyridazino[4,3‐f][1,4]oxazepin‐12(13H)‐ones; Pharmacology. Drug treatments; Pyridazino; Pyridazino[3,4‐b][1,5]benzoxazepin‐5(6H)‐ones; Lactam; Tetracyclic compound; Tricyclic compound; Screening test; In vitro; Mycobacterium tuberculosis; Structure activity relation; Mycobacteriales; Mycobacteriaceae; Bacteria; Actinomycetes; Antituberculous agent; Aromatic compound; Antibacterial agent; Chemical synthesis; Oxygen nitrogen heterocycle
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/1521-4184(20007)333:7<231::AID-ARDP231>3.0.CO;2-1

Starting from substituted 3,6‐dichloropyridazine‐4‐carboxamides (2, 3) tri‐ and tetracyclic compounds (4, 5) could be smoothly prepared. Structural modifications of interest with regard to biological activity were performed by N‐alkylation and reductive dehalogenation. The new substituted heterocyclic compounds were screened as antimycobacterial agents; the influence of the substitution pattern on activity is discussed.