Synthesis and Anti-inflammatory Activity of Alkyl/Arylidene-2-aminobenzothiazoles and 1-Benzothiazol-2-yl-3-chloro-4-substituted-azetidin-2-ones

Abstract

Ten new derivatives of 1-benzothiazol-2-yl-3-chloro-4-substituted-azetidin-2-ones (3a-j) were synthesized using various Schiff bases (alkyl/arylidene-2-aminobenzothiazoles; 2a-j), which in turn were prepared starting from 2-aminobenzothiazole (1). All the synthesised compounds were characterised by elemental analyses and spectral (IR, 1H-NMR, 13C-NMR and EI-MS) data. The title compounds 2a-j and 3a-j were screened in vivo using carrageenan-induced rat paw edema model. All the test compounds showed anti-inflammatory activity when tested in vivo. In general, compounds 3a-j were found to be more potent compared to compounds 2a-j. Among the compounds tested, compound 2g in the alkyl/arylidene-2-aminobenzothiazoles series and compound 3 g in the 1-benzothiazol-2-yl-3-chloro-4-substituted-azetidin-2-ones series were found to be the most potent. All the test compounds were also evaluated to check the gastric ulcer incidence. In gastric ulceration studies, all the test compounds were generally found to be safe at the 100 mg/kg dose level. Furthermore the most potent compounds 2 g and 3 g from each series were screened in vitro for inhibition of both COX-2 and COX-1 catalysed prostaglandin biosynthesis (radiochemical assay). Like most of the commercially available non-steroidal anti-inflammatory drugs (NSAIDs), in the in vitro study, compounds 2 g and 3 g showed anti-inflammatory activity by blocking the metabolism of arachidonic acid to prostaglandin via the cyclooxygenase pathways. In general, in the vitro assay, test compounds 2 g and 3 g were found to be more active after 15 min pre-incubation with the enzyme. Compound 3 g was found to be more COX-2 selective, while compound 2 g was found to be equally COX-2 and COX-1 selective.

Syntheses, Characterization and Antimicrobial Activities of 1-(1H-benzo[d][1,2,3]triazol-1-yl)-2-(((3aR,5R)-3--5- disubstituted -3,3a-dihydro-2H-pyrazolo[3,4-d]thiazol-6(5H)-yl)amino)ethanone derivatives

“…A mixture of compound 7-12 (0.01 mol), hydrazine hydrate (0.01 mol) and anhydrous NaOAc (0.005 mol) in anhydrous glacial AcOH (50 mL), was refluxed for 3 h. The reaction mixture was concentrated and then poured in to ice cold water, the solid thus separated was filtered, washed with water and recrystallised from glacial AcOH to afford pure brown colour solid (13)(14)(15)(16)(17)(18). Their characteristic analytical data are given in Table 1.…”

“…Thiazolidine moiety is well known for biological [9][10][11][12] and pharmacological activities [13][14][15][16][17] such as CNS stimulant anthelmintic 18 , antibacterial 19 , mosquito repellant 20 , analgesic [21][22] , diurals, antiinflammatory, antifungal 18,23 , hypnotic, amoebicidal 24 , anticonvulsant 25 and nematocidal, antitubercular 26 etc.…”

Identification of a bacteria-produced benzisoxazole with antibiotic activity against multi-drug resistant Acinetobacter baumannii

“…Although uncommonly reported from natural sources, benzisoxazole scaffolds are well represented in pharmacology, having shown significant importance in anti-HIV [14], antimicrobial [15][16][17][18], antipsychotic [19,20], antiinflammatory [17,21,22], antioxidation [17,23], anticancer [23][24][25][26], anticonvulsant [27] and antidiabetic [28,29] research. Moreover, 1,2-benzisoxazole derivatives, which include zonisamide, risperidone, paliperidone, and iloperidone, are all FDA approved and currently in use for epilepsy, mood disorders, and schizophrenia, respectively [30][31][32][33].…”