Preparation of novel derivatives of pyridothiazine-1,1-dioxide and their CNS and antioxidant properties.
Starting from isothiazolopyridine-1,1-dioxide (1), corresponding derivatives of 3-aryl-4-hydroxypyrido[3,2-e]-1,2-thiazine-1,1-dioxide (6) possessing the 3-[4-(substituted-phenyl)piperazinyl]propyl or 3-(4-substituted-piperidinyl)propyl side chain by the nitrogen atom of the thiazine ring were prepared. Under pharmacological central nervous system (CNS) screening in animal models (mice), all of the six pyridothiazines 6 tested exhibited analgesic action as the predominant profile of their activity ('writhing' test 12.5-50 mg/kg). Moreover, the radical scavenging activity against peroxyl radicals of the representative pyridothiazines 6 was evaluated in vitro in water environment and some of them proved to be moderate antioxidants.
Malinka
W
W
Department of Chemistry of Drugs, Wrocław Medical University, Poland. malinka@bf.uni.wroc.pl
Kaczmarz
M
M
Filipek
B
B
Sapa
J
J
Glod
B
B
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002490:Central Nervous System / Q000187:drug effects*; D004357:Drug Synergism; D004487:Edema / Q000188:drug therapy; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010087:Oxides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010147:Pain Measurement; D010545:Peroxides / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013874:Thiopental / Q000008:administration & dosage / Q000494:pharmacology
D000700:Analgesics; D000975:Antioxidants; D010087:Oxides; D010545:Peroxides; D013843:Thiazines; C049375:perhydroxyl radical; D013874:Thiopental