69206-89-9

Usage

Uses

Used in Pharmaceutical Industry:
4-Amino-6-piperidinopyrimidine is used as a building block for the development of MNK1/2 inhibitors, which are targeted cancer therapies. These inhibitors play a crucial role in regulating the MAPK signaling pathway, which is often dysregulated in cancer cells, leading to uncontrolled cell growth and proliferation. By inhibiting MNK1/2, these compounds can potentially suppress tumor growth and enhance the effectiveness of cancer treatments.

InChI:InChI=1/C9H14N4/c10-8-6-9(12-7-11-8)13-4-2-1-3-5-13/h6-7H,1-5H2,(H2,10,11,12)

Upstream product

• 110-89-4 piperidine 
• 5305-59-9 4-amino-6-chloropyrimidine 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of pyridone–aminal derivatives as MNK1/2 inhibitors

Excessive phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) plays a major role in the dysregulation of mRNA translation and the activation of tumor cell signaling. eIF4E is exclusively phosphorylated by mitogen-activated protein kinase interacting kinases 1 and 2 (MNK1/2) on Ser209. So, MNK1/2 inhibitors could decrease the level of p-eIF4E and regulate tumor-associated signaling pathways. A series of pyridone–aminal derivatives were synthesized and evaluated as MNK1/2 inhibitors. Several compounds exhibited great inhibitory activity against MNK1/2 and selected compounds showed moderate to excellent anti-proliferative potency against hematologic cancer cell lines. In particular, compound 42i (MNK1 IC50 = 7.0 nM; MNK2 IC50 = 6.1 nM) proved to be the most potent compound against TMD-8 cell line with IC50 value of 0.91 μM. Furthermore, 42i could block the phosphorylation level of eIF4E in CT-26 cell line, and 42i inhibited the tumor growth of CT-26 allograft model significantly. These results indicated that compound 42i was a promising MNK1/2 inhibitor for the potent treatment of colon cancer.