title: Medicinal chemistry and properties of 1,2,4-thiadiazoles.
abstract: 1,2,4-Thiadiazole is a distinctive class of small heterocyclic thiol trapping agents that serve as an interesting pharmacophore in the design of inhibitors targeting the cysteine residues of proteins. X-Ray crystal structures of enzyme-inhibitor complex indicate that the cysteine thiol reacts with the N-S bond of the thiadiazole moiety to form a disulfide bond resulting in the inactivation of the enzymes. This review addresses the medicinal chemistry and various properties of 1,2,4-thiadiazoles in their potential as new electrophilic "warheads" for targeting the cysteine residues of biomolecules (e.g, H+/K+ ATPase), and cysteine-dependent enzymes (e.g., cathepsin B and transglutaminase).
authors.affiliation: Apotex Research, Inc. Medicinal Chemistry Department, 400 Ormont Drive, Toronto, ON, M9L 1N9, Canada. ttam@apotex.com
authors.forename: Tim Fat
authors.initials: TF
authors.lastname: Tam
authors.forename: Regis
authors.initials: R
authors.lastname: Leung-Toung
authors.forename: Wanren
authors.initials: W
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Spino
authors.forename: Khashayar
authors.initials: K
authors.lastname: Karimian
mesh_terms: D002401:Cathepsin B / Q000737:chemistry / Q000187:drug effects; D003545:Cysteine / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry / Q000187:drug effects; D013830:Thiadiazoles / Q000737:chemistry* / Q000494:pharmacology*; D011503:Transglutaminases / Q000737:chemistry / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D013830:Thiadiazoles; D011503:Transglutaminases; D002401:Cathepsin B; D017506:H(+)-K(+)-Exchanging ATPase; D003545:Cysteine