Novel design principle validated: Glucopyranosylidene-spiro-oxathiazole as new nanomolar inhibitor of glycogen phosphorylase, potential antidiabetic agent

Glucose derived inhibitors of glycogen phosphorylase

“…Combining these facts with the spirobicyclic structure of hydantoins, a novel design principle for efficient glucose-based inhibitors of GP could be set up [69,70] : 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 such molecules should have a rigid spirobicyclic scaffold in which a (preferably five-membered hetero) cycle is attached to the anomeric carbon of D-glucopyranose; this cycle, although it may, should not necessarily be a Hbond donor towards His 377; a suitably oriented, large aromatic appendage must be present on this cycle to fit into the b-channel.…”

Click Inspired Synthesis of 1,2,3‐Triazole‐linked 1,3,4‐Oxadiazole Glycoconjugates

“…Also, considering the involvement of carbohydrates in various interactions, sugars are often incorporated in various simpler molecules to deal with the targeting mechanism of action and/or pharmacology . 1,3,4‐Oxadiazoles linked to sugar skeleton such as a glucofuranose, glucopyranose, xylopyranose, psicopyranose, thioglycosides and fructopyranose are documented in literature, and many of these derivatives have showed potential antibacterial, anticancer, antitumor, and antidiabetic activity . Considering the aforementioned facts and our previous experience on click‐mediated development of glycoconjugates of diverse application , we intend to conjugate the orthogonally protected saccharide residue with biologically privileged 1,3,4‐oxadiazole framework using Cu(I)‐catalyzed click reaction to obtain glycohybrids, which may exhibit the medicinal properties of both the parent components.…”

Synthesis of C-xylopyranosyl- and xylopyranosylidene-spiro-heterocycles as potential inhibitors of glycogen phosphorylase

“…Among the recently designed and synthesized 5-b-D-glucopyranosyl-3-substituted-1,2,4-triazoles submicromolar inhibitors of GP (e.g., G) were found. 22,23 Best compounds in series of other types of anomeric spirocycles like isoxazolines 24 (e.g., H) and oxathiazoles 25,26 (e.g.,…”