Hybrid compounds from chalcone and 1,2-benzothiazine pharmacophores as selective inhibitors of alkaline phosphatase isozymes

2-Benzylidenebenzofuran-3(2H)-ones as a new class of alkaline phosphatase inhibitors: synthesis, SAR analysis, enzyme inhibitory kinetics and computational studies

“…In recent years, several inhibitors of APs based on biaryl sulfonamide, chromone, triazole and coumarin sulfonate motifs have been reported. [25][26][27][28][29][30][31][32] APs have become important target enzymes owing to their considerable pharmacological importance in medicinal chemistry. 33,34a,b Some compounds were found to be effective inhibitors of AP, but most of them inhibited APs non-selectively.…”

Basicity-Tuned Reactivity: diaza-[1,2]-Wittig versus diaza-[1,3]-Wittig Rearrangements of 3,4-Dihydro-2H-1,2,3-benzothiadiazine 1,1-Dioxides

“…When seeking mechanistic information on the reaction starting from compound 1a , we realized that depending on the basicity of the system (i.e., on the amount of t -BuOK applied), the reaction could result either in the previously described benzisothiazole 2a or in an unexpected benzothiazine derivative 3a (Scheme ), the latter being again a molecular framework in the focus of recent pharmacological interest. − Hereby we explore the mechanism of this highly complex reaction and demonstrate that it is possible to selectively influence the outcome of the reaction toward any of the two different products. The corresponding experimental and computational studies are described below, with further details disclosed in the Supporting Information (SI).…”

Recent Advances in Synthesis and Medicinal Evaluation of 1,2‐Benzothiazine Analogues

“…Ashraf and co-workers fused these eccentric molecules with 1,2-benzothiazines (whose pharmacological applications have been discussed earlier) to increase the specific inhibition of ALPs. [82] The team studied the inhibition of derivatives 186 a-o towards h-TNALP and h-IALP isozymes of alkaline phosphatase (Table 18). Their synthesis can be achieved by aldol condensation of already reported compounds 110 (Scheme 18) with appropriate aldehydes in alkaline medium.…”

“…The remarkable features of these heterocycles can be witnessed by their large number of publications (1782) and citations (11592) in recent times. Here in this review, therapeutic applications of 1,2‐benzothiazines in the arena of anti‐inflammatory, [23–37] anticancer, [38–56] antimicrobial, [57–62] antioxidant, [56,58,63–66] antidiabetic, [67–74] nor‐A efflux pump inhibitor, [75] antiepileptic, [76] anti‐arthritis, [77] anti‐HIV‐1, [78–81] alkaline phosphate inhibitors, [82] anti‐monoamine oxidase, [83] anti‐11β‐hydroxysteroid dehydrogenase, [84–85] calpain‐1 inhibitors, [86–87] and hepatitis virus‐C [88–89] along with their corresponding synthesis have been visualized. The prominence attained by derivatives of thiazole [90–91] and thiazine [15,92] lead researchers to construct medications like alpelisib and prochlorperazine maleate and a lot more (Figure 1).…”