- Structure-based drug designing, scoring, and synthesis of some substituted sulphonylureas/guanidine-based derivatives as hypoglycemic agents
-
Objective: The present work deals with the designing, scoring, synthesis and, characterization of 1-(4-(2-(4-Substitutedphenylamino)-2-oxoethyl)phenylsulfonyl)-3-(4-substitutedbenzoyl)urea (5A-5B),1-(4-(2-(4-substitutedphenylamino)-2-oxoethyl)phenylsulfonyl)-3-(4-substituted-benzoyl)guanidine(5C-5E) and, 1-(4-Substitutedbenzoyl)-3-(4-(2-oxo-2-(piperazin-1-yl)ethyl)phenylsulfonyl)urea (5F-5H) based derivatives as hypoglycemic agents. Methods: Docking calculations were performed to predict the binding affinity between the AKR1C1 complexes and sulphonylureas compounds using the Glide docking program. Docking studies on LigPrep treated ligands were carried out to predict the binding pocket of protein 4YVP using the docking program. The QikProp program was used to predict the ADME/T properties of the analogues. All these newly synthesized compounds were screened for their in vivo hypoglycemic activity by most relevant animal models like alloxan-induced diabetic rats by measuring blood plasma concentration compared with reference drug glibenclamide. Results: Novel compounds 1-(4-(2-(4-Substitutedphenylamino)-2-oxoethyl)phenylsulfonyl)-3-(4-substitutedbenzoyl)urea (5A-5B), 1-(4-(2-(4-substitutedphenylamino)-2-oxoethyl)phenylsulfonyl)-3-(4-substitutedbenzoyl) guanidine (5C-5E), and 1-(4-Substitutedbenzoyl)-3-(4-(2-oxo-2-(piperazin-1-yl)ethyl)phenylsulfonyl)urea (5F-5H) were synthesised and characterized using spectral and analytical data. The results of molecular docking and in vivo hypoglycemic activity, all compounds have shown considerable activity with respect to glibenclimide, but compounds 5D (52.49±7.73) and 5E(48.18±4.22)are equipotent with respect to activity as compared to standard glibenclamide(55.97±3.19). Conclusion: Compounds 5D and 5E have exhibited good hypoglycemic activity,hence both the derivatives will consider as a lead molecule and further some modification in their structures to get a more potent anti-diabetic agent.
- Panchal, Ishan,Sen, Dhrubo Jyoti,Navle, Archana,Shah, Umang
-
p. 226 - 232
(2017/12/12)
-
- CARBONIC ANHYDRASE INHIBITORS. 9. INHIBITORS WITH MODIFIED SULFONAMIDO GROUPS AND THEIR INTERACTION WITH THE ZINC ENZYME
-
A number of 20 compounds, containing modified sulfonamido groups were prepared and tested as carbonic anhydrase inhibitors on the bovine enzyme. Novel classes of inhibitors were evidenced, and a new mode of binding for bidentate inhibitors was proposed, both for the native and Co(II) substituted enzyme.
- Supuran, Claudiu T.,Banciu, Mircea D.
-
p. 1345 - 1354
(2007/10/03)
-
- Ring-expansion of Azidobenzenesulphonamides and Azidobenzamides
-
4-Azidobenzenesulphonamides and 2- and 4-azidobenzamides undergo phototransformation to 2-alkoxy-3H-azepines in alcohols but the yields are low.Ring-expansion of 4-azidobenzenesulphonamide and 4-azidobenzenesulphonylguanidine in aqueous tetrahydrofuran to 3H-azepin-2(1H)-ones proceeds via a singlet nitrene pathway; thermolysis of 4-azidobenzenesulphonamide in aqueous dioxane gave only the triplet-derived product, sulphanilamide.Efficient de-azidation of 4-azidobenzesulphonamides and 4-azidobenzamides can be accomplished by heating the azides at 105 deg C in hydrazine hy drate.The crystallographic analysis of 5-sulphamoyl-3H-azepin-2(1H)-one shows the molecule to be non-planar with the azepine ring puckered in a boat form.The lactam configuration is confirmed with the carbonyl group having a bond length of 1.231 Angstroem.
- Brown, Thomas B.,Lowe, Philip R.,Schwalbe, Carl H.,Stevens, Malcolm F.G.
-
p. 2485 - 2490
(2007/10/02)
-
