1-4-benzothiazine has been researched along with Disease-Models--Animal* in 2 studies
2 other study(ies) available for 1-4-benzothiazine and Disease-Models--Animal
| Article | Year |
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Developing potential agents against atherosclerosis: Design, synthesis and pharmacological evaluation of novel dual inhibitors of oxidative stress and Squalene Synthase activity.
For the treatment of multifactorial and complex diseases, it has become increasingly apparent that compounds acting at multiple targets often deliver superior efficacy compared to compounds with high specificity for only a single target. Based on previous studies demonstrating the important antioxidant and anti-hyperlipidemic effect of morpholine and 1,4-benzo(x/thi)azine derivatives (A-E), we hereby present the design, synthesis and pharmacological evaluation of novel dual-acting molecules as a therapeutic approach for atherosclerosis. Analogues 1-10 were rationally designed through structural modifications of their parent compounds (A-E) in order for structure-activity relationship studies to be carried out. Most compounds showed a significant inhibition against Squalene Synthase activity exhibiting at the same time a very potent multimodal antioxidant (against lipid peroxidation and as free-radical scavengers) effect, thus bringing to light the 2-aryl-1,4-benzo(x/thia)zin-2-ol scaffold as an outstanding pharmacophore for the design of potent antioxidants. Finally, the replacement of the octahydro-1,4-benzoxazine moiety of lead compound D with its respective 1,4-benzothiazine (compound 4), although conserved (anti-hypercholesterolemic) or even improved (anti-hyperlipidemic) activity, did not preserve the anti-diabetic effect of D. Topics: Animals; Atherosclerosis; Cyclooxygenase 1; Cyclooxygenase 2; Diabetes Mellitus, Type 2; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Design; Enzyme Inhibitors; Farnesyl-Diphosphate Farnesyltransferase; Humans; Hypolipidemic Agents; Male; Mice; Mice, Hairless; Molecular Structure; Morpholines; Oxidative Stress; Rats; Structure-Activity Relationship; Thiazines | 2017 |
Novel ketoconazole analogues based on the replacement of 2,4-dichlorophenyl group with 1,4-benzothiazine moiety: design, synthesis, and microbiological evaluation.
As a part of a program to develop novel antifungal agents, new compounds which incorporate the 1,4-benzothiazine moiety into the structure of ketoconazole (KTZ) were prepared. These compounds were computationally investigated to assess whether the 1,4-benzothiazine moiety was a suitable bioisosteric replacement for the 2,4-dichlorophenyl group of KTZ in order to obtain a more potent inhibition of CYP51 enzyme of Candida albicans. Results of preliminary microbiological studies show that the racemic cis-7 analogue has a good in vivo activity, comparable to that of KTZ, but the best activity was observed in the racemic trans-7 analogue. Topics: Animals; Candida albicans; Candidiasis; Crystallography, X-Ray; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Disease Models, Animal; Enzyme Inhibitors; Female; Fungal Proteins; Hydrocarbons, Chlorinated; Immunologic Tests; Ketoconazole; Kidney; Mice; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Stereoisomerism; Structure-Activity Relationship; Thiazines | 2006 |