467470-45-7Relevant academic research and scientific papers
Discovery of n-phenyl-4-(1h-pyrrol-3-yl)pyrimidin-2-amine derivatives as potent mnk2 inhibitors: Design, synthesis, sar analysis, and evaluation of in vitro anti-leukaemic activity
Abdelaziz, Ahmed M.,Diab, Sarah,Islam, Saiful,Basnet, Sunita K. C.,Noll, Benjamin,Li, Peng,Mekonnen, Laychiluh B.,Lu, Jingfeng,Albrecht, Hugo,Milne, Robert W.,Gerber, Cobus,Yu, Mingfeng,Wang, Shudong
, p. 600 - 621 (2019/08/30)
Background: Aberrant expression of eukaryotic translation initiation factor 4E (eIF4E) is common in many types of cancer including acute myeloid leukaemia (AML). Phosphorylation of eIF4E by MAPK-interacting kinases (Mnks) is essential for the eIF4E-mediated oncogenic activity. As such, the pharmacological inhibition of Mnks can be an effective strategy for the treatment of cancer. Methods: A series of N-phenyl-4-(1H-pyrrol-3-yl)pyrimidin-2-amine derivatives was designed and synthesised. The Mnk inhibitory activity of these derivatives as well as their anti-proliferative activity against MV4-11 AML cells was determined. Results: These compounds were identified as potent Mnk2 inhibitors. Most of them demonstrated potent anti-proliferative activity against MV4-11 AML cells. The cellular mechanistic studies of the representative inhibitors revealed that they reduced the level of phosphorylated eIF4E and induced apoptosis by down-regulating the anti-apoptotic protein myeloid cell leukaemia 1 (Mcl-1) and by cleaving poly(ADP-ribose)polymerase (PARP). The lead compound 7k possessed desirable pharmacokinetic properties and oral bioavailability. Conclusion: This work proposes that exploration of the structural diversity in the context of N-phenyl-4-(1H-pyrrol-3-yl)pyrimidin-2-amine would offer potent and selective Mnk inhibitors.
Synthesis and biological activity of 2-anilino-4-(1H-pyrrol-3-yl) pyrimidine CDK inhibitors
Wang, Shudong,Wood, Gavin,Meades, Christopher,Griffiths, Gary,Midgley, Carol,McNae, Iain,McInnes, Campbell,Anderson, Sian,Jackson, Wayne,Mezna, Mokdad,Yuill, Rhoda,Walkinshaw, Malcolm,Fischer, Peter M.
, p. 4237 - 4240 (2007/10/03)
A series of 2-anilino-4-(1H-pyrrol-3-yl)pyrimidines were prepared and evaluated for their ability to inhibit cyclin-dependent kinases (CDKs). A number of analogues were found to be potent CDK2 and CDK4 inhibitors and to exhibit anti-proliferative activity
