35966-84-8Relevant articles and documents
Discovery of selective fragment-sized immunoproteasome inhibitors
Kollár, Levente,Gobec, Martina,Szilágyi, Bence,Proj, Matic,Knez, Damijan,ábrányi-Balogh, Péter,Petri, László,Imre, Tímea,Bajusz, Dávid,Ferenczy, Gy?rgy G.,Gobec, Stanislav,Keser?, Gy?rgy M.,Sosi?, Izidor
, (2021/04/23)
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 in-house 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 biologically 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.
TROPOMYOSIN RECEPTOR KINASE (TRK) DEGRADATION COMPOUNDS AND METHODS OF USE
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Page/Page column 349-350, (2021/09/04)
This disclosure relates to bivalent compounds (e.g., bi-functional small molecule compounds), compositions comprising one or more of the bivalent compounds, and to methods of use the bivalent compounds for the treatment of certain disease in a subject in need thereof. The disclosure also relates to methods for identifying such bivalent compounds.
Synthesis and fungicidal activity of novel imidazo[4, 5-b]pyridine derivatives
Wu, Daoxin,Liu, Minhua,Li, Zhong,Dang, Mingming,Liu, Xingping,Li, Jianming,Huang, Lu,Ren, Yeguo,Zhang, Zai,Liu, Weidong,Liu, Aiping
, p. 8 - 14 (2019/05/21)
A series of novel imidazo[4,5-b]pyridine derivatives were synthesized and their structures were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. The results of bioassays showed that some compounds exhibit good fungicidal activity against Puccinia polysora In particular, compound 7b showed an EC50 value of 4.00 mg/L, which was comparable with that of tebuconazole. Besides, preliminary structure-activity relationship was discussed.