452056-82-5Relevant articles and documents
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.
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
