Kollar, Levente; Gobec, Martina; Szilagyi, Bence; Proj, Matic; Knez, Damijan; Abranyi-Balogh, Peter; Petri, Laszlo; Imre, Timea; Bajusz, David; Ferenczy, Gyorgy G.; Gobec, Stanislav; Keseru, Gyorgy M.; Sosic, Izidor published an article in 2021. The article was titled 《Discovery of selective fragment-sized immunoproteasome inhibitors》, and you may find the article in European Journal of Medicinal Chemistry.Reference of 1H-Benzo[d]imidazol-2-amine The information in the text is summarized as follows:
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. The results came from multiple reactions, including the reaction of 1H-Benzo[d]imidazol-2-amine(cas: 934-32-7Reference of 1H-Benzo[d]imidazol-2-amine)
1H-Benzo[d]imidazol-2-amine(cas: 934-32-7) can be used in the hydrolysis of a choline carbonate. It was also used in the synthesis of imidazo[1,2-a]benzimidazoles.Reference of 1H-Benzo[d]imidazol-2-amine
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem