Non-enzymatic reduction of a 1,2,4-thiadiazolium derivative

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 6; pp. 2172 - 2178
• Main Authors: Zhang, Fa, Estavillo, Carmelita, Mohler, Margie, Cai, Jane
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.03.2008; Elsevier
• Subjects: 1,2,4-Thiodiazolines; 1-[(2-Methoxy-phenyl)-(2-methoxy-phenylimino)-methyl]-3-phenyl-thiourea; 2,3-Bis-(2-methoxy-phenyl)-5-phenylamino-[1,2,4]-thiadiazolium bromide; Animals; Antioxidants - pharmacology; Ascorbic Acid - pharmacology; Biological and medical sciences; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Chromatography, High Pressure Liquid; Cysteine - pharmacology; Degradation; General pharmacology; Glutathione - pharmacology; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Medical sciences; Melanocortin; Molecular Structure; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Rats; Rats, Sprague-Dawley; Reduction; Science & Technology; Spectrometry, Mass, Electrospray Ionization; Swine; Thiourea - analogs & derivatives; Thiourea - chemistry; Thiourea - isolation & purification; 1,2,4-Thiodiazolines; Degradation; Melanocortin; Reduction; 2,3-Bis-(2-methoxy-phenyl)-5-phenylamino-[1,2,4]-thiadiazolium bromide; 1-[(2-Methoxy-phenyl)-(2-methoxy-phenylimino)-methyl]-3-phenyl-thiourea; 1,2,4-thiodiazolines; degradation; 2,3-bis-(2-methoxy-phenyl)-5-phenylamino-[1,2,4]-thiadiazolium bromide; reduction; 1-[(2-methoxy-phenyl)-(2-methoxy-phenylimino)-methyl]-3-phenyl-thiourea; melanocortin; Biological fluid; Cysteine; Ascorbic acid; Rat; Vitamin; Tripeptide; Thioureas; Blood; Blood plasma; Chemical reduction; 1-[(2-Methoxy-phenyl)-(2-methoxy-phenylimino)- methyl]-3-phenyl-thiourea; Ungulata; Glutathione; Modulator; Rodentia; Metabolism; Melanocortin receptor; Pig; Sulfur containing aminoacid; Vertebrata; Mammalia; Sulfur peptide; Animal; Artiodactyla; Pharmacokinetics
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2008.01.029

2,3-Bis-(2-methoxy-phenyl)-5-phenylamino-[1,2,4]-thiadiazolium bromide ( 1), a 1,2,4-thiadiazolium derivative, was reduced to the corresponding imidoylthiourea, 1-[(2-methoxy-phenyl)-(2-methoxy-phenylimino)-methyl]-3-phenyl-thiourea ( 3), by some biological interesting reducing reagents including glutathione, cysteine, and ascorbic acid. The reduction also occurred in Sprague–Dawley rat and Yorkshire swine plasma. Chemical trapping studies suggested that thiol containing biological molecules existing in the plasma are mainly responsible for this reaction. A facile method for preparation of 3 from 1 was established by using 2-thioethanol as a reaction reagent as well as a solvent. Those new findings could shed lights on the development of 1,2,4-thiadiazolium derivatives for their potential pharmaceutical applications. It was discovered that 2,3-bis-(2-methoxy-phenyl)-5-phenylamino-[1,2,4]-thiadiazolium bromide ( 1), a 1,2,4-thiadiazolium derivative, could be reduced to the corresponding imidoylthiourea, 1-[(2-methoxy-phenyl)-(2-methoxy-phenylimino)-methyl]-3-phenyl-thiourea ( 3), by some biologically interesting reducing reagents including glutathione, cysteine, and ascorbic acid. The reduction also occurred in Sprague–Dawley rat and Yorkshire swine plasma, suggesting that thiol containing biological molecules existing in the plasma are mainly responsible for this reaction. A facile method for preparation of 3 from 1 was established by using 2-thioethanol as reaction reagent as well as solvent. The structure of 3 was fully characterized using nuclear magnetic resonance (NMR) and mass spectrometry with electrospray ionization source (ESI-MS). Those new findings could shed light on the development of 1,2,4-thiadiazolium derivatives for their potential pharmaceutical applications.