450368-25-9

Usage

Uses

2-Anilinopyrimidine-5-carboxylic Acid can be used for useful organic synthesis.

InChI:InChI=1/C11H9N3O2/c15-10(16)8-6-12-11(13-7-8)14-9-4-2-1-3-5-9/h1-7H,(H,15,16)(H,12,13,14)

Upstream product

• 886365-88-4 (5-bromo-pyrimidin-2-yl)-phenyl-amine 
• 937796-09-3 C₁₂H₁₁N₃O₂ 
• 864172-93-0 ethyl 2-(phenylamino)pyrimidine-5-carboxylate 

Downstream Products

• 1581701-32-7 N-(2-methyl-5-((4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)phenyl)-2-(phenylamino)pyrimidine-5-carboxamide 

Relevant academic research and scientific papers

Synthesis and structure-activity relationship of thiol-based histone deacetylase 6 inhibitors

Selective histone deacetylase 6 (HDAC6) inhibitors are safe and well-tolerated with less off-target effect. However, most available HDAC6 inhibitors contain hydroxamate as a zinc-binding group (ZBG), and their unfavorable pharmacokinetic properties along with potential genotoxicity limited wide application in diverse diseases. Therefore, we designed and synthesized a series of selective HDAC6 inhibitors utilizing thiol as the ZBG and discussed their structure-activity relationship based on molecular docking. In particular, compound 21, obtained by constantly step-by-step simplification and evolution based on Ricolinostat, a specific HDAC6 inhibitor in Phase II, unexpectedly showed high selectivity (29-fold) and moderate potency (73?nM). Utilizing pyrimidine as a linker in thiol-based HDAC6 inhibitors produces an utterly novel structure, which might display different pharmacokinetic properties and genotoxicity.

Identification and optimization of new dual inhibitors of B-Raf and epidermal growth factor receptor kinases for overcoming resistance against vemurafenib

Epidermal growth factor receptor (EGFR) amplification has been demonstrated to be critical for the inherent and/or acquired resistance against current B-RafV600E inhibitor therapy for melanoma and colorectal cancer patients. We describe the discovery and structure-activity relationship study of a series of 1H-pyrazolo[3,4-b]pyridine-5-carboxamide analogues as novel dual inhibitors of EGFR and B-RafV600E mutant. One of the most promising compounds, 6a, potently inhibited both of the kinases with IC50 values of 8.0 and 51 nM, respectively. The compound also strongly suppressed the proliferation of a panel of intrinsic and acquired resistant melanoma and/or colorectal cancer cells harboring overexpressed EGFR with submicromolar IC 50 values. Further mechanism investigation revealed that 6a could sustainably inhibit the activation of the MAPK path way in the resistant SK-MEL-28 PR30 melanoma cancer cells and WiDr colorectal cancer cells with EGFR amplification. Our results support the hypothesis that the EGFR/B-Raf V600E dual inhibition might be a tractable strategy to overcome the intrinsic and acquired resistance of melanoma and/or colorectal cancers against the current B-RafV600E inhibitor therapy.