title: Synthesis and biological evaluation of some novel urea and thiourea derivatives of isoxazolo[4,5-d]pyridazine and structurally related thiazolo[4,5-d]pyridazine as antimicrobial agents.
abstract: This study reports the synthesis of some novel isoxazolo[4,5-d]pyridazines and structurally related thiazolo[4,5-d]pyridazines, and their biological evaluation as antimicrobial agents. The proposed compounds were designed to contain pharmacophores such as urea, thiourea, sulfonylurea (thiourea) and some derived functionalities that are believed to contribute to the anticipated biological activities. The results revealed that 25 compounds displayed broad spectrum of antibacterial activity, with greater inhibitory effect on the growth of the tested Gram positive strains compared to Gram negative ones. Moreover, 14 compounds were able to produce appreciable growth inhibitory activity against Candida albicans fungus when compared to Clotrimazole. Most of the tested isoxazolo[4,5-d]pyridazines displayed better antimicrobial profile than their corresponding thiazolo[4,5-d]pyridazine congeners. Four compounds namely, p-(3,7-dimethyl-4-oxo-4H-isoxazolo [4,5-d]pyridazine-5-yl)benzenesulfonylthioureas (11c-d), 3-substituted-2-[p-(3,7-dimethyl-4-oxo-4H-isoxazolo[4,5-d]pyridazine-5-yl)-benzene-sufonylimino]-4-oxothiazolidines (13d) and p-(2,7-dimethyl-4-oxo-4H-thiazolo[4,5-d]pyridazin-5-yl)benzenesulfonylthiourea (24c) were found to be most active antimicrobial members in present study.
authors: Department of Chemistry, Faculty of Science, King Abdulaziz University, P O Box 80203, Jeddah, 21589, Saudi Arabia, hfaidallahm@hotmail.com.
authors: Hassan M
authors: HM
authors: Faidallah
authors: Sherif A F
authors: SA
authors: Rostom
authors: Salem A
authors: SA
authors: Basaif
authors: Mohammed S T
authors: MS
authors: Makki
authors: Khalid A
authors: KA
authors: Khan
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives*; D014508:Urea / Q000031:analogs & derivatives*
chemical_list: D000890:Anti-Infective Agents; D011724:Pyridazines; D014508:Urea; D013890:Thiourea