479691-87-7

Upstream product

• 71406-74-1 N-benzylmethyl-2-chloropyrimidin-4-amine 
• 1296135-47-1 tert-butyl 4-[4-(benzylamino)pyrimidin-2-yl]piperazine-1-carboxylate 

Relevant academic research and scientific papers

Design, synthesis and structure-activity relationship (SAR) studies of 2,4-disubstituted pyrimidine derivatives: Dual activity as cholinesterase and Aβ-aggregation inhibitors

A novel class of 2,4-disubstituted pyrimidines (7a-u, 8a-f, 9a-e) that possess substituents with varying steric and electronic properties at the C-2 and C-4 positions, were designed, synthesized and evaluated as dual cholinesterase and amyloid-β (Aβ)-aggregation inhibitors. In vitro screening identified N-(naphth-1-ylmethyl)-2-(pyrrolidin-1-yl)pyrimidin-4-amine (9a) as the most potent AChE inhibitor (IC50 = 5.5 μM). Among this class of compounds, 2-(4-methylpiperidin-1-yl)-N-(naphth-1-ylmethyl)pyrimidin- 4-amine (9e) was identified as the most potent and selective BuChE inhibitor (IC50 = 2.2 μM, selectivity index = 11.7) and was about 5.7-fold more potent compared to the commercial, approved reference drug galanthamine (BuChE IC50 = 12.6 μM). In addition, the selective AChE inhibitor N-benzyl-2-(4-methylpiperazin-1-yl)pyrimidin-4-amine (7d), exhibited good inhibition of hAChE-induced aggregation of Aβ1-40 fibrils (59% inhibition). Furthermore, molecular modeling studies indicate that a central pyrimidine ring serves as a suitable template to develop dual inhibitors of cholinesterase and AChE-induced Aβ aggregation thereby targeting multiple pathological routes in AD.

Design, synthesis and structure-activity relationship studies of a focused library of pyrimidine moiety with anti-proliferative and anti-metastasis activities in triple negative breast cancer

Triple-negative breast cancer (TNBC) is a clinical conundrum with distinct clinical and pathologic features, which is characterized by high aggression, poor prognosis, and lack of targeted therapies. In this study, based on the structural features of type II kinase inhibitors, we designed and synthesized a focused library of 41 pyrimidine derivatives possessing potent anti-proliferation activity, Y29 showed the most potent activity against MDA-MB-231 cells. Subsequently, we carried out target prediction, homology modeling, molecular docking, dynamics simulation and determination of enzymatic activity. The results suggested that PDGFR-β was its potential target. In vitro experiments revealed that Y29 attenuated metastasis by PDGFR-β inhibition-induced autophagy and could enhance autophagy-related cell death through AKT-MAPK feedback loop in MDA-MB-231 cells.

5-HT receptor ligands and uses thereof

Compounds of Formula (IA) that act as 5-HT receptor ligands and their uses in the treatment of diseases linked to the activation of 5-HT2 receptors in animals are described herein.