65069-48-9Relevant academic research and scientific papers
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
, 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.
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.
Improved Procedures for the Preparation of Cycloalkyl-, Arylalkyl-, and Arylthioureas
Rasmussen, C. R.,Villani, F. J.,Weaner, L. E.,Reynolds, B. E.,Hood, A. R.,et al.
, p. 456 - 459 (2007/10/02)
An improved procedure for the preparation of arylthioureas consists of the reaction of benzoyl isothiocyanate with anilines in acetone and debenzoylation of the resultant N-aryl-N'-benzoylthioureas with 5percent aqueous sodium hydroxide.Bicycloalkylthioureas and N-(arylalkyl)thioureas (e.g. 9H-9-fluorenylthiourea) are directly prepared from the corresponding isothiocyanates and ammonia.
Nitrogen heterocyclic carboximidamide compounds
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, (2008/06/13)
5-, 6- or 7-Membered fully saturated 1-azacarbocyclic-2-ylidene derivatives of guanidine having anti-secretory and hypoglycemic activities, and further useful for treatment of cardiovascular disease states.
