Facile synthesis of coumarin bioisosteres—1,2-benzoxathiine 2,2-dioxides

7-Aryl-triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrase IX and XII

“…The general strategy of Zabulovski's group 1,9 for the preparation of 6-substituted sulfocoumarins was recently validated by us for the synthesis of 7-substituted such derivatives. As reported 40 , the regioselective protection of the commercially available 2,4-dihydroxybenzaldehyde 4, followed by intramolecular cyclization and aromatization, afforded the desired 7-hydroxysulfocoumarin 5, which finally was converted to the derivative 6 through reaction with propargyl bromide (Scheme 1).…”

“…The design of sulfocoumarins as CA inhibitors (CAIs) was inspired by their corresponding bioisosters coumarins [2][3][4][5][6][7][8][9] , whose inhibition mechanism relies on the CA-mediated esterase activity. Indeed the sulfocoumarins, as well as coumarins, undergo a CA-mediated hydrolysis within the active site cavity with the generation of the inhibitory species.…”

“…Many synthetic efforts have been made for the development of specific CAIs: in the last 15 years, in addition to the classical ''tail approach'' [10][11][12][13][14][15][16][17][25][26][27][28] which is mainly applied to classical sulfonamide inhibitors and their isosters, novel CAIs scaffolds have been also identified such as the polyamines 29 , phenols [30][31][32] , dithiocarbamates [33][34][35][36] , xanthates 37 , coumarins, thiocoumarins, 2-thioxocoumarins, coumarine oximes 4,38,39 . Sulfocoumarins are the latest CAI class identified and similarly to the coumarins showed the most selective inhibition profiles against the pathologically valuable CA isoforms 1,9,[40][41][42][43][44] . In analogy to coumarins, the substitution pattern at the sulfocoumarin scaffolds strongly influences the potency and selectivity profile against different hCA isoforms 1, [40][41][42][43][44] .…”

Deciphering the Mechanism of Human Carbonic Anhydrases Inhibition with Sulfocoumarins: Computational and Experimental Studies

“…The novel sulfocoumarins 10 – 14 were obtained by applying the general synthetic strategy firstly reported by Zalubovski's group (Scheme ) …”

One-pot catalyst-free synthesis of 3-heterocyclic coumarins

“…They possess versatile biological activities and can be found in many natural or synthetic drug molecules [1][2][3][4][5][6]. Moreover, coumarin derivatives are characterized by sufficient fluorescence in the visible light range, large Stokes shift, high quantum yield of photoluminescence, and reasonable solubility, making them some of the most extensively investigated and commercially significant organic fluorescent materials [7][8][9][10][11].…”