35966-84-8Relevant academic research and scientific papers
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.
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.
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.
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.
C2-Selective Branched Alkylation of Benzimidazoles by Rhodium(I)-Catalyzed C-H Activation
Tran, Ga?l,Confair, Danielle,Hesp, Kevin D.,Mascitti, Vincent,Ellman, Jonathan A.
, p. 9243 - 9252 (2017/09/11)
Herein, we report a Rh(I)/bisphosphine/K3PO4 catalytic system allowing for the first time the selective branched C-H alkylation of benzimidazoles with Michael acceptors. Branched alkylation with N,N-dimethyl acrylamide was successfully applied to the alkylation of a broad range of benzimidazoles incorporating a variety of N-substituents and with both electron-rich and -poor functionality displayed at different sites of the arene. Moreover, the introduction of a quaternary carbon was achieved by alkylation with ethyl methacrylate. The method was also shown to be applicable to the C2-selective branched alkylation of azabenzimidazoles.
3 - methylamino - 4 - nitro phenoxyethanol preparation method
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Paragraph 0036; 0037, (2017/08/25)
The invention relates to a method for preparing 3-methylamino-4-nitrophenoxyethanol. The method comprises the steps of performing methylamination reaction by using 2,4-dichloronitrobenzene as a raw material and using methanol as a solvent to obtain 3-methylamino-4-nitrochlorobenzene, performing nucleophilic substitution with a sodium hydroxide (or other alkaline matter) solution of ethylene glycol to substitute the remaining other chlorine group so as to obtain crude 3-methylamino-4-nitrophenoxyethanol, and performing re-crystallization to obtain high-purity 3-methylamino-4-nitrophenoxyethanol. The process of preparing the 3-methylamino-4-nitrochlorobenzene intermediate through a one-step method replaces a two-step method process of preparing the intermediate through high pressure ammonolysis of 2,4-dichloronitrobenzene and N-methylation reaction; in addition, methanol is adopted in the one-step method to replace a tetrahydrofuran solution, so that the purposes of reducing the recovery cost and reducing the cost of the solvent are achieved; the method has the characteristics of conventional equipment, simplicity in operation, cheap and readily available raw materials, low cost, high yield and the like.
N2,N4-BIS(4-(PIPERAZINE-1-YL)PHENYL)PIRIMIDINE-2,4-DIAMINE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT FOR PREVENTING OR TREATING CANCER
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Paragraph 0102; 0106, (2015/07/02)
The present invention relates to a N2,N4-bis(4-(piperazine-1-yl)phenyl)pirimidine-2,4-diamine derivative or a pharmaceutically acceptable salt thereof, and to a composition containing same as an active ingredient for preventing or treating cancer. Since the compound according to the present invention has good effects in inhibiting the activities of anaplastic lymphoma kinase (ALK) and activated Cdc42-associated kinase (ACK1), the compound can have improved therapeutic effects against cancer cells having ALK fusion proteins such as EML4-ALK and NPM-ALK and is expected to be effective in preventing the recurrence of cancer. Therefore, the compound can be effectively used as a composition for preventing or treating cancer.
N2,N4-BIS(4-(PIPERAZINE-1-YL)PHENYL)PIRIMIDINE-2,4-DIAMINE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT FOR PREVENTING OR TREATING CANCER
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Paragraph 0244; 0245, (2015/06/10)
Disclosed herein are a new N2,N4-bis(4-(piperazin-1-yl)phenyl)pyrimidin-2,4-diamine derivative or a pharmaceutically acceptable salt thereof and a pharmaceutical composition for the prevention or treatment of cancers containing the same as an active ingredient. The compound of the present invention has excellent inhibitory effects against the activities of anaplastic lymphoma kinase (ALK) and activated cdc42-associated kinase (ACK1) and thus can improve the therapeutic effects on the treatment of cancer cells having anaplastic lymphoma kinase fusion proteins such as EML4-ALK and NPM-ALK, and also effectively prevent the recurrence of cancers thus being useful as a pharmaceutical composition for the prevention and treatment of cancers.
Conformation-based restrictions and scaffold replacements in the design of hepatitis C virus polymerase inhibitors: Discovery of deleobuvir (BI 207127)
LaPlante, Steven R.,B?s, Michael,Brochu, Christian,Chabot, Catherine,Coulombe, René,Gillard, James R.,Jakalian, Araz,Poirier, Martin,Rancourt, Jean,Stammers, Timothy,Thavonekham, Bounkham,Beaulieu, Pierre L.,Kukolj, George,Tsantrizos, Youla S.
supporting information, p. 1845 - 1854 (2014/04/03)
Conformational restrictions of flexible torsion angles were used to guide the identification of new chemotypes of HCV NS5B inhibitors. Sites for rigidification were based on an acquired conformational understanding of compound binding requirements and the roles of substituents in the free and bound states. Chemical bioisosteres of amide bonds were explored to improve cell-based potency. Examples are shown, including the design concept that led to the discovery of the phase III clinical candidate deleobuvir (BI 207127). The structure-based strategies employed have general utility in drug design.
