914660-36-9Relevant articles and documents
Design, synthesis and evaluation of 2-aminothiazole derivatives as sphingosine kinase inhibitors
Vogt, Dominik,Weber, Julia,Ihlefeld, Katja,Brüggerhoff, Astrid,Proschak, Ewgenij,Stark, Holger
, p. 5354 - 5367 (2014/12/11)
Sphingosine kinases (SphK1, SphK2) are main regulators of sphingosine-1-phosphate (S1P), which is a pleiotropic lipid mediator involved in numerous physiological and pathophysiological functions. SphKs are targets for novel anti-cancer and anti-inflammatory agents that can promote cell apoptosis and modulate autoimmune diseases. Herein, we describe the design, synthesis and evaluation of an aminothiazole class of SphK inhibitors. Potent inhibitors have been discovered through a series of modifications using the known SKI-II scaffold to define structure-activity relationships. We identified N-(4-methylthiazol-2-yl)-(2,4′-bithiazol)-2′-amine (24, ST-1803; IC50values: 7.3 μM (SphK1), 6.5 μM (SphK2)) as a promising candidate for further in vivo investigations and structural development.
Multi-dimensional target profiling of N,4-diaryl-1,3-thiazole-2-amines as potent inhibitors of eicosanoid metabolism
R?dl, Carmen B.,Vogt, Dominik,Kretschmer, Simon B.M.,Ihlefeld, Katja,Barzen, Sebastian,Brüggerhoff, Astrid,Achenbach, Janosch,Proschak, Ewgenij,Steinhilber, Dieter,Stark, Holger,Hofmann, Bettina
supporting information, p. 302 - 311 (2014/08/05)
Eicosanoids like leukotrienes and prostaglandins play a considerable role in inflammation. Produced within the arachidonic acid (AA) cascade, these lipid mediators are involved in the pathogenesis of pain as well as acute and chronic inflammatory diseases like rheumatoid arthritis and asthma. With regard to the lipid cross-talk within the AA pathway, a promising approach for an effective anti-inflammatory therapy is the development of inhibitors targeting more than one enzyme of this cascade. Within this study, thirty N-4-diaryl-1,3-thiazole-2- amine based compounds with different substitution patterns were synthesized and tested in various cell-based assays to investigate their activity and selectivity profile concerning five key enzymes involved in eicosanoid metabolism (5-, 12-, 15-lipoxygenase (LO), cyclooxygenase-1 and -2 (COX-1/-2)). With compound 7, 2-(4-phenyl)thiazol-2-ylamino)phenol (ST-1355), a multi-target ligand targeting all tested enzymes is presented, whereas compound 9, 2-(4-(4-chlorophenyl)thiazol-2-ylamino)phenol (ST-1705), represents a potent and selective 5-LO and COX-2 inhibitor with an IC50 value of 0.9 ± 0.2 μM (5-LO) and a residual activity of 9.1 ± 1.1% at 10 μM (COX-2 product formation). The promising characteristics and the additional non-cytotoxic profile of both compounds reveal new lead structures for the treatment of eicosanoid-mediated diseases.
THIAZOLE COMPOUNDS AND METHODS OF USE
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Page/Page column 63, (2010/11/24)
The present invention provides compounds, salts and hydrates of Formula I, wherein the variables Ar1R2, R3, R4, r, q, and t are defined herein. Certain compounds of Formula I described herein possess potent antiviral activity. The invention also provides compounds of Formula I that are potent and/ or selective inhibitors of Hepatitis C virus replication. Certain compounds described herein inhibit assembly of the HCV replication complex. The invention also provides pharmaceutical compositions containing one or more compounds of Formula I, or a salt, solvate, or acylated prodrug of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents. The invention further comprises methods of treating patients suffering from certain infectious diseases by administering to such patients an amount of a compound of Formula I effective to reduce signs or symptoms of the disease. These infectious diseases include viral infections, particularly HCV infections. The invention is particularly includes methods of treating human patients suffering from an infectious disease, but also encompasses methods of treating other animals, including livestock and domesticated companion animals, suffering from an infectious disease. Methods of treatment include administering a compound of Formula I as a single active agent or administering a compound of Formula I in combination with on or more other therapeutic agent.
