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

• Published in: Archives of pharmacal research Vol. 36; no. 11; pp. 1354 - 1368
• Main Authors: Faidallah, Hassan M., Rostom, Sherif A. F., Basaif, Salem A., Makki, Mohammed S. T., Khan, Khalid A.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-11-2013; 대한약학회
• Subjects: Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Medicine; Microbial Sensitivity Tests; Molecular Structure; Pharmacology/Toxicology; Pharmacy; Pyridazines - chemical synthesis; Pyridazines - chemistry; Pyridazines - pharmacology; Research Article; Structure-Activity Relationship; Thiourea - analogs & derivatives; Urea - analogs & derivatives; 약학; Urea; pyridazine; Antimicrobial activity; Synthesis; Thiazolo[4,5; Thiourea; Isoxazolo[4,5
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-013-0144-0

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-4
H
-isoxazolo [4,5-
d
]pyridazine-5-yl)benzenesulfonylthioureas (
11c
–
d
), 3-substituted-2-[
p
-(3,7-dimethyl-4-oxo-4
H
-isoxazolo[4,5-
d
]pyridazine-5-yl)-benzene-sufonylimino]-4-oxothiazolidines (
13d
) and
p
-(2,7-dimethyl-4-oxo-4
H
-thiazolo[4,5-
d
]pyridazin-5-yl)benzenesulfonylthiourea (
24c
) were found to be most active antimicrobial members in present study.