452056-83-6Relevant academic research and scientific papers
Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases
Albrecht, Wolfgang,Unger, Anke,Bauer, Silke M.,Laufer, Stefan A.
, p. 5290 - 5305 (2017/07/22)
The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38α MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs, and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha release. For reconfirming the findings of the animal studies when administering 1 to healthy human volunteers, a phase I clinical trial was conducted. Apart from further information regarding the pharmacokinetic and pharmacodynamic characteristics of 1, it was demonstrated that dual inhibition of p38α MAPK and PDE4 is able to synergistically attenuate the excessive anti-inflammatory response.
Tetra-substituted pyridinylimidazoles as dual inhibitors of p38α mitogen-activated protein kinase and c-jun N-terminal kinase 3 for potential treatment of neurodegenerative diseases
Muth, Felix,Günther, Marcel,Bauer, Silke M.,D?ring, Eva,Fischer, Sabine,Maier, Julia,Drückes, Peter,K?ppler, Jürgen,Trappe, J?rg,Rothbauer, Ulrich,Koch, Pierre,Laufer, Stefan A.
supporting information, p. 443 - 456 (2015/07/27)
Tetra-substituted imidazoles were designed as dual inhibitors of c-Jun N-terminal kinase (JNK) 3 and p38α mitogen-activated protein (MAP) kinase. A library of 45 derivatives was prepared and evaluated in a kinase activity assay for their ability to inhibi
Imidazole compounds having an antiinflammatory effect
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Page/Page column 15, (2008/06/13)
The invention relates to 2-sulfinyl- or 2-sulfonyl-substituted imidazole derivatives of the formula I in which the radicals R1, R2, R3 and R4 have the meaning indicated in the description. The compounds of the i
Tetrasubstituted imidazole inhibitors of cytokine release: Probing substituents in the N-1 position
Laufer, Stefan A.,Zimmermann, Werner,Ruff, Kathrin J.
, p. 6311 - 6325 (2007/10/03)
We prepared novel 1,2,4,5-tetrasubstituted imidazole derivatives with high anti-inflammatory activity by using our previously described regiospecific synthesis. Systematic optimization of the imidazole N-1 substituent resulted in compound 9b that potently
Identification of regioisomers in a series of N-substituted pyridin-4-yl imidazole derivatives by regiospecific synthesis, GC/MS, and 1H NMR
Wagner, Gerd K.,Kotschenreuther, Dunja,Zimmermann, Werner,Laufer, Stefan A.
, p. 4527 - 4530 (2007/10/03)
The regiospecific synthesis of 2a (Scheme 3), a novel and potent pyridinyl imidazole inhibitor of p38 MAP (mitogen-activated protein) kinase, and the regioselective preparation of its regioisomer 2b (Scheme 4) are described. Chromatographic and spectroscopic data are presented, which in this class of compounds allow the unambiguous identification of regioisomers prepared by a nonregiospecific synthetic strategy. Biological data demonstrating the importance of the correct regiochemistry for inhibition of p38 are given.
Ones, thiones, and N-oxides: An eercise in imidazole chemistry
Laufer, Stefan,Wagner, Gerd,Kotschenreuther, Dunja
, p. 2290 - 2293 (2007/10/03)
Regioselective synthetic approaches to tetrasubstituted imidazoles (see picture) are reported. These highly substituted heterocycles are potent inhibitors of cytokine release and therefore interesting candidates for anti-inflammatory drugs.
