Kollar, Levente published the artcileDiscovery of selective fragment-sized immunoproteasome inhibitors, Formula: C6H6OS, the main research area is immunoproteasome inhibitor benzooxazolethione benzothiazolethione benzimidazolethione chymotrypsin subunit binding SAR; Chloro scan; Disulfide formation; Electrophilic warheads; Fragments; Immunoproteasome; Thiones.
Proteasomes contribute to maintaining protein homeostasis and their inhibition is beneficial in certain types of cancer and in autoimmune diseases. However, the inhibition of the proteasomes in healthy cells leads to unwanted side-effects and significant effort has been made to identify inhibitors specific for the immunoproteasome, especially to treat diseases which manifest increased levels and activity of this proteasome isoform. Here, we report our efforts to discover fragment-sized inhibitors of the human immunoproteasome. The screening of an inhouse library of structurally diverse fragments resulted in the identification of benzo[d]oxazole-2(3H)-thiones, benzo[d]thiazole-2(3H)-thiones, benzo[d]imidazole-2(3H)-thiones, and 1-methylbenzo[d]imidazole-2(3H)-thiones (with a general term benzoXazole-2(3H)-thiones) as inhibitors of the chymotrypsin-like (β5i) subunit of the immunoproteasome. A subsequent structure-activity relationship study provided us with an insight regarding growing vectors. Binding to the β5i subunit was shown and selectivity against the β5 subunit of the constitutive proteasome was determined Thorough characterization of these compounds suggested that they inhibit the immunoproteasome by forming a disulfide bond with the Cys48 available specifically in the β5i active site. To obtain fragments with biol. more tractable covalent interactions, we performed a warhead scan, which yielded benzoXazole-2-carbonitriles as promising starting points for the development of selective immunoproteasome inhibitors with non-peptidic scaffolds.
European Journal of Medicinal Chemistry published new progress about Benzothiazoles Role: PAC (Pharmacological Activity), THU (Therapeutic Use), BIOL (Biological Study), USES (Uses). 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Formula: C6H6OS.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem