New Carriers for Representative Peptides and Peptide Drugs

Abstract

3,5-Disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivatives; 4a-g were prepared and found to be a promising prodrug approach for peptide drugs. The pH profile for their degradation in aqueous buffer solutions was determined using HPLC technique and accounted for, in terms of specific base-catalyzed reactions. All of the compounds however, showed high acid-stability. Enzymatic (human serum) hydrolysis of the different derivatives offered an advantageous range of t1/2's, the property that permits controlling onset and duration of actions of drugs.

Synthesis, in vitro urease inhibitory activity and molecular docking of 3,5‐disubstituted thiadiazine‐2‐thiones

“…Benzylamine (2.18 mL, 20 mmol) and glycine (1.5 g, 20 mmol): recrystallized from ethanol, colourless solid, Yield = 72%, m.p = 135‐137°C; UV (methanol) λ max nm: 205, 290; IR (KBr) υ max cm −1 : 3430 (COOH), 3030 (Aromatic–C–H), 2883 (Aliphatic–C–H), 1724 (C═O), 1491 (C═S); 1 H NMR (CDCl 3 + CD 3 OD) δ: 7.29‐7.21 (m, 5H, Ar‐H), 5.22 (s, 2H, C 6 H 5 CH 2 ), 4.39 (s, 2H, H‐4), 4.29 (s, 2H, H‐6), 3.29 (s, 2H, NCH 2 COOH); 13 C NMR (CD 3 OD) δ: 194.5 (C═S), 172.2 (C═O), 136.9 (Ar‐C), 129.8, 129.5, and 129.1 (Ar–CH), 69.7 (C‐4), 59.7 (C‐6), 54.5 (CH 2 C 6 H 5 ), 51.9 (NCH 2 ); EI‐MS; m/z (rel. int.…”

“…In addition to its renowned biological potential, this versatile heterocyclic nucleus has been reported as a biolabile prodrug, in the drug delivery system (DDS) because of its characteristic features like high liphophilicity and enzymatic hydrolysis. Subsequently, different types of amino acids, peptides, and drug based on primary amine have been reported to successfully attached to the THTT moiety, which further enhance their cellular uptake by improving lipophilicity in the area where various physiological and enzyme activities causes the release of the drug molecule.…”

New 2H-Tetrahydro-1, 3, 5-thiadiazine-2-thiones Incorporating Glycine and Glycinamide as Potential Antifungal Agents

“…It was suggested that the reaction proceeds through the formation of the intermediates (3 a-i) in situ [11][12][13][14][15][16]. One of these intermediates, 3 c, was isolated by using 40 % KOH (instead of 20 % KOH, see Experimental to provide a concentrated solution inducing crystallization of 3 c after addition of the required amount of formaldehyde.…”

Synthesis and antifungal activity of 3,3'-ethylenebis(5-alkyl-1,3,5-thiadiazine-2-thiones)

“…It was suggested that the reaction proceeds through the formation of the intermediate (2) in situ [12][13][14][15] . Structures of the synthesized compounds were verified on the basis of spectral and elemental methods of analyses.…”