185312-82-7Relevant academic research and scientific papers
Compound serving as protein kinase inhibitor and application of compound
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Paragraph 0263-0266, (2021/04/07)
The invention discloses a compound used as a protein kinase inhibitor and application of the compound, the compound has an obvious inhibition effect on protein kinase activity, can be used as a BTK inhibitor for preparing medicines for treating BTK-mediated diseases such as malignant tumors, autoimmune diseases and the like, and has wide application prospect.
Catalytic Access to Functionalized Allylic gem-Difluorides via Fluorinative Meyer–Schuster-Like Rearrangement
An, Rui,Li, Huimin,Liao, Lihao,Wu, Jin-Ji,Xu, Yang,Zhao, Xiaodan
supporting information, p. 11010 - 11019 (2020/05/18)
An unprecedented approach for efficient synthesis of functionalized allylic gem-difluorides via catalytic fluorinative Meyer–Schuster-like rearrangement is disclosed. This transformation proceeded with readily accessible propargylic fluorides, and low-cost B–F reagents and electrophilic reagents by sulfide catalysis. A series of iodinated, brominated, and trifluoromethylthiolated allylic gem-difluorides that were difficult to access by other methods were facilely produced with a wide range of functional groups. Importantly, the obtained iodinated products could be incorporated into different drugs and natural products, and could be expediently converted into many other valuable gem-difluoroalkyl molecules as well. Mechanistic studies revealed that this reaction went through a regioselective fluorination of alkynes followed by a formal 1,3-fluorine migration under the assistance of the B–F reagents to give the desired products.
5-Aryl-1,3,4-oxadiazol-2-ylthioalkanoic Acids: A Highly Potent New Class of Inhibitors of Rho/Myocardin-Related Transcription Factor (MRTF)/Serum Response Factor (SRF)-Mediated Gene Transcription as Potential Antifibrotic Agents for Scleroderma
Kahl, Dylan J.,Hutchings, Kim M.,Lisabeth, Erika Mathes,Haak, Andrew J.,Leipprandt, Jeffrey R.,Dexheimer, Thomas,Khanna, Dinesh,Tsou, Pei-Suen,Campbell, Phillip L.,Fox, David A.,Wen, Bo,Sun, Duxin,Bailie, Marc,Neubig, Richard R.,Larsen, Scott D.
, p. 4350 - 4369 (2019/05/08)
Through a phenotypic high-throughput screen using a serum response element luciferase promoter, we identified a novel 5-aryl-1,3,4-oxadiazol-2-ylthiopropionic acid lead inhibitor of Rho/myocardin-related transcription factor (MRTF)/serum response factor (SRF)-mediated gene transcription with good potency (IC50 = 180 nM). We were able to rapidly improve the cellular potency by 5 orders of magnitude guided by sharply defined and synergistic SAR. The remarkable potency and depth of the SAR, as well as the relatively low molecular weight of the series, suggests, but does not prove, that binding to the unknown molecular target may be occurring through a covalent mechanism. The series nevertheless has no observable cytotoxicity up to 100 μM. Ensuing pharmacokinetic optimization resulted in the development of two potent and orally bioavailable anti-fibrotic agents that were capable of dose-dependently reducing connective tissue growth factor gene expression in vitro as well as significantly reducing the development of bleomycin-induced dermal fibrosis in mice in vivo.
INHIBITORS OF RHO/MRTF/SRF-MEDIATED GENE TRANSCRIPTION AND METHODS FOR USE OF THE SAME
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Paragraph 0067; 0112-0112, (2019/10/20)
Disclosed herein are inhibitors of Rho/MRTF/SRF-mediated gene transcription, and methods for their use in treating or preventing diseases such as cancer and fibrosis. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically accept
Stilbene Boronic Acids Form a Covalent Bond with Human Transthyretin and Inhibit Its Aggregation
Smith, Thomas P.,Windsor, Ian W.,Forest, Katrina T.,Raines, Ronald T.
, p. 7820 - 7834 (2017/10/06)
Transthyretin (TTR) is a homotetrameric protein. Its dissociation into monomers leads to the formation of fibrils that underlie human amyloidogenic diseases. The binding of small molecules to the thyroxin-binding sites in TTR stabilizes the homotetramer and attenuates TTR amyloidosis. Herein, we report on boronic acid-substituted stilbenes that limit TTR amyloidosis in vitro. Assays of affinity for TTR and inhibition of its tendency to form fibrils were coupled with X-ray crystallographic analysis of nine TTR·ligand complexes. The ensuing structure-function data led to a symmetrical diboronic acid that forms a boronic ester reversibly with serine 117. This diboronic acid inhibits fibril formation by both wild-type TTR and a common disease-related variant, V30M TTR, as effectively as does tafamidis, a small-molecule drug used to treat TTR-related amyloidosis in the clinic. These findings establish a new modality for covalent inhibition of fibril formation and illuminate a path for future optimization.
3-(PYRIDIN-3-YL)-ACRYLAMIDE AND N-(PYRIDIN-3-YL)-ACRYLAMIDE DERIVATIVES AND THEIR USE AS PAK OR NAMPT MODULATORS
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Paragraph 00353, (2017/03/14)
The invention generally relates to cyclic compounds and, more particularly, to a compound represented by Structural Formula I: or a pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the multicyclic compounds. The invention also relates to a method for treating a disease or disorder selected from cancer (e.g., lymphoma, such as mantle cell lymphoma), a neurodegenerative disease, an inflammatory diseases or an immune system disease (e.g., a T- Cell mediated autoimmune diseases) in a subject in need thereof. The method comprises administering to a subject in need thereof a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a composition comprising a compound of the invention, or a pharmaceutically acceptable salt thereof.
IMMUNE ADJUSTMENT COMPOUND, USE THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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Paragraph 0063; 0064, (2016/08/29)
The present invention provides a compound represented by formula I, wherein R is a halogen element or a C1-C6 alkyl group. The compound has S1 P1 receptor agonist activity and selective specificity and has obviously-shortened half-life in-vivo, and therefore the compound is a high-quality second-generation S1P1 receptor agonist. The present invention also provides a use of the compound in preparing medicine for treating diseases or symptoms mediated by an S1P1 receptor, a pharmaceutical composition comprising the compound, and uses of the compound and the pharmaceutical composition in treating diseases or symptoms mediated by the S1 P1 receptor.
TRIAZOLYL PYRIMIDINONE COMPOUNDS AS PDE2 INHIBITORS
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Page/Page column 49; 50, (2016/10/04)
The present invention is directed to pyrimidine carboxamide compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
Rational design of a novel AMPA receptor modulator through a hybridization approach
Caldwell, Nicola,Harms, Jonathan E.,Partin, Kathryn M.,Jamieson, Craig
supporting information, p. 392 - 396 (2015/04/27)
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a family of glutamate ion channels of considerable interest in excitatory neurotransmission and associated disease processes. Here, we demonstrate how exploitation of the availa
FATTY ACID SYNTHASE INHIBITORS
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Page/Page column 87, (2014/01/18)
This invention relates to novel spirocyclic piperidines according to Formula (I) which are inhibitors of fatty acid synthase (FAS), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the treatment of cancers.
