80967-50-6Relevant academic research and scientific papers
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.
Substituted N-phenylisothioureas: Potent inhibitors of human nitric oxide synthase with neuronal isoform selectivity
Shearer, Barry G.,Lee, Shuliang,Oplinger, Jeffrey A.,Frick, Lloyd W.,Garvey, Edward P.,Furfine, Eric S.
, p. 1901 - 1905 (2007/10/03)
S-Ethyl N-phenylisothiourea (4) has been found to be a potent inhibitor of both the human constitutive and inducible isoforms of nitric oxide synthase. A series of substituted N-phenylisothiourea analogues was synthesized to investigate the structure-activity relationship of this class of inhibitor. Each analogue was evaluated for human isoform selectivity. One analogue, S-ethyl N-[4-(trifluoromethyl)phenyl]isothiourea (39), exhibited 115-fold and 29-fold selectivity for the neuronal isoform versus the inducible and endothelial derived constitutive isoforms, respectively. Studies have shown the substituted N-phenylisothiourea 39 binds competitively with L,-arginine.
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.
