401950-86-5

Upstream product

• 351317-28-7 ethyl 3-hydroxy-4-fluorobenzoate 
• 3040-44-6 1-piperidinoethanol 
• 401950-85-4 4-fluoro-3-(2-methoxy-ethoxy)-benzoic acid ethyl ester 

Downstream Products

• 401950-88-7 2-amino-5-(2-methoxy-ethoxy)-4-(2-piperidin-1-yl-ethoxy)-benzoic acid ethyl ester 
• 401950-87-6 5-(2-methoxy-ethoxy)-2-nitro-4-(2-piperidin-1-yl-ethoxy)-benzoic acid ethyl ester 

Relevant academic research and scientific papers

Nitrogenous heterocyclic compounds

The present invention relates to nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof which have inhibitory activity on the phosphorylation of kinases, which inhibits the activity of such kinases. The invention is also related to a method of inhibiting kinases and treating diseases states in a mammal by inhibiting the phosphorylation of kinases. In a particular aspect the present invention provides nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof which inhibit phosphorylation of PDGF receptor to hinder abnormal cell growth and cell wandering, and a method for preventing or treating cell-proliferative diseases such as arteriosclerosis, vascular reobstruction, cancer and glomerulosclerosis.

Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase family

We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of highly potent, specific, orally active, small molecule kinase inhibitors directed against members of PDGFR receptor have been developed through modifications of the novel quinazoline template I. Systematic modifications in the A-bicyclic ring and D-rings of protype I were carried out to afford potent analogues, which display IC50 values of 50 values of 50-200 nM, whereas 15-20-fold less potent activity against CSF1R was observed. This analogue also inhibits autophosphorylation of Flt-3 ligand-stimulated wild-type Flt-3 and a constitutively activated Flt-3/internal tandem duplication (ITD) with IC50 values of 30-100 nM. Through this optimization process, 75 was found to be metabolically stable and has desirable pharmacokinetic properties in all animal species studied (F% > 50%, T1/2 > 8 h). Oral administration of 75 promotes mice survival and significantly delayed disease progression in a Flt-3/ITD-mediated leukemia mouse model and shows efficacy in a nude mouse model of chronic myelomonocytic leukemia.