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Upstream product

• 16153-81-4 4-(4-Methyl-piperazino)-anilin 
• 16155-03-6 1-methyl-4-(4-nitrophenyl)piperazine 
• 330550-98-6 N⁴-cyclopentyl-N²-(4-(4-methylpiperazin-1-yl)phenyl)-5-nitropyrimidine-2,4-diamine 
• 1003-03-8 Cyclopentamine 
• 330551-07-0 4-cyclopentylamino-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5-aminopyrimidine 
• 103-72-0 phenyl isothiocyanate 
• 330550-92-0 2-chloro-N-cyclopentyl-5-nitropyrimidin-4-amine 
• 109-01-3 1-methyl-piperazine 

Relevant academic research and scientific papers

ARYLAMINO PURINE DERIVATIVES, PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF

Arylamino purine derivatives represented by formula I and their preparation method are disclosed, wherein each substituent is defined as in the description. The derivatives have an inhibitory effect on non-small cell lung cancer with deletion mutation of exon 19 or L858R point mutation of exon 21 in epidermal growth factor receptor (EGFR).

Structural optimization and structure-activity relationships of N 2-(4-(4-methylpiperazin-1-yl)phenyl)- N 8-phenyl-9 H -purine-2,8-diamine derivatives, a new class of reversible kinase inhibitors targeting both EGFR-activating and resistance mutations

This paper describe the structural optimization of a hit compound, N 2-(4-(4-methylpiperazin-1-yl)phenyl)-N8-phenyl-9H-purine- 2,8-diamine (1), which is a reversible kinase inhibitor targeting both EGFR-activating and drug-resistance (T790M) mutations but has poor binding affinity. Structure-activity relationship studies led to the identification of 9-cyclopentyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)-N 8-phenyl-9H-purine-2,8-diamine (9e) that exhibits significant in vitro antitumor potency against the non-small-cell lung cancer (NSCLC) cell lines HCC827 and H1975, which harbor EGFR-activating and drug-resistance mutations, respectively. Compound 9e was further assessed for potency and selectivity in enzymatic assays and in vivo anti-NSCLC studies. The results indicated that compound 9e is a highly potent kinase inhibitor against both EGFR-activating and resistance mutations and has good kinase spectrum selectivity across the kinome. In vivo, oral administration of compound 9e at a dose of 5 mg/kg caused rapid and complete tumor regression in a HCC827 xenograft model, and an oral dose of 50 mg/kg initiated a considerable antitumor effect in an H1975 xenograft model.