title: 2-Substituted-3-oxoisothiazolo[5,4-b]pyridines as potential central nervous system and antimycobacterial agents.
abstract: The 2-[3-(substituted-amino)-2-hydroxypropyl]-4,6-dimethyl-3-oxo-2,3- dihydroisothiazolo[5,4-b]pyridines 3 were synthesized and pharmacologically evaluated in animal models. The preliminary pharmacological screening study showed that the investigated compounds were toxic and had no significant activity in central nervous system (CNS) tests. Additionally, compounds 3, and several other 2-substituted-4,6- dimethyl-3-oxo-2,3-dihydroisothiazolo[5,4-b]pyridines described here (2), together with those (4) reported in a previous paper, were evaluated in vitro against Mycobacterium tuberculosis H37Rv. For comparison, products of the rearrangement of some isothiazolopyridine 1,1-dioxides (4a,b) with the corresponding pyrido[3,2-e]-1,2-thiazines (5a,b) and different N2-substituted derivatives of the latter (5c-i) were also prepared and investigated in antimycobacterial tests. The most potent antituberculars of the 23 compounds assayed are 2-[3-(4-benzylpiperidin-1-yl)-2-hydroxypropyl]-4,6-dimethyl-3-oxo- 2,3- dihydroisothiazolo[5,4-b]pyridine 3d and ethyl (4,6-dimethyl-3-oxo-2,3-dihydroisothiazolo[5,4-b]pyridin-2-yl)acet ate 4c (MIC < 12.5 micrograms/ml, 100 and 98% inhibition, respectively).
authors.affiliation: Department of Chemistry of Drugs, Wrocław University of Medicine, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Malinka
authors.forename: S
authors.initials: S
authors.lastname: Ryng
authors.forename: M
authors.initials: M
authors.lastname: Sieklucka-Dziuba
authors.forename: G
authors.initials: G
authors.lastname: Rajtar
authors.forename: A
authors.initials: A
authors.lastname: Głowniak
authors.forename: Z
authors.initials: Z
authors.lastname: Kleinrok
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D014151:Anti-Anxiety Agents; D000995:Antitubercular Agents; D011725:Pyridines