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.
INHIBITORS OF FIBROBLAST GROWTH FACTOR RECEPTOR KINASES
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Paragraph 00667-00669; 00688-00689, (2021/12/28)
Provided herein are heteroaryl inhibitors of fibroblast growth factor receptor kinases, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.
NOVEL OXOQUINOLIZINE COMPOUNDS FOR THE TREATMENT AND PROPHYLAXIS OF BACTERIAL INFECTION
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Page/Page column 34, (2019/12/25)
The present invention relates to novel compounds of formula (I), wherein R1, R2, R3, R4, R5, R6 and R7 are as described herein, and their pharmaceutically 5 acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.
