title: Synthesis of some pyrrolo[3,4-d]pyridazinones and their preliminary anticancer, antimycobacterial and CNS screening.
abstract: Starting from 1-substituted-2,5-dimethyl-3,4-pyrroledicarboxylic acid anhydrides 1 and N-methylhydrazine, 1,2,3,4-tetrahydro-6-substituted-2,5,7-trimethyl-6H-pyrrolo[3,4-d]pyridazin- 1,4-ones 2 were prepared. Reaction of compounds 2 with alkylating agents give 3-N- or 4-O-alkylated products 3, 4 or mixtures of these isomers in ratios depending on the alkylating agents. Under preliminary pharmacological screening two of four new pyrrolo[3,4-d]pyridazinones were active as cystostatic agents, all the eight compounds displayed moderate activity against Mycobacterium tuberculosis and two compounds were active as CNS-depressive agents.
authors.affiliation: Department of Chemistry of Drugs, Wrocław Medical University, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Malinka
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D010147:Pain Measurement / Q000187:drug effects; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D011930:Reaction Time / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000700:Analgesics; D000970:Antineoplastic Agents; D000995:Antitubercular Agents; D002491:Central Nervous System Agents; D011724:Pyridazines; D011758:Pyrroles