940304-53-0

Upstream product

• 940304-54-1 3-(2-chloro-4-{[5-(2-hydroxyethyl)-5H-pyrrolo[3,2-d]-pyrimidin-4-yl]amino}phenoxy)benzoic acid 
• 75-64-9 tert-butylamine 
• 884171-79-3 methyl 3-(2-chloro-4-nitrophenoxy)benzoate 
• 350-30-1 3-chloro-4-fluoronitrobenzene 
• 19438-10-9 methyl 3-hydroxybenzoate 

Relevant academic research and scientific papers

Design and synthesis of pyrrolo[3,2- d ]pyrimidine human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors: Exploration of novel back-pocket binders

To develop novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) kinase inhibitors, we explored pyrrolo[3,2-d]pyrimidine derivatives bearing bicyclic fused rings designed to fit the back pocket of the HER2/EGFR proteins. Among them, the 1,2-benzisothiazole (42m) ring was selected as a suitable back pocket binder because of its potent HER2/EGFR binding and cell growth inhibitory (GI) activities and pseudoirreversibility (PI) profile as well as good bioavailability (BA). Ultimately, we arrived at our preclinical candidate 51m by optimization of the N-5 side chain to improve CYP inhibition and metabolic stability profiles without a loss of potency (HER2/EGFR inhibitory activity, IC50, 0.98/2.5 nM; and GI activity BT-474 cells, GI50, 2.0 nM). Reflecting the strong in vitro activities, 51m exhibited potent tumor regressive efficacy against both HER2- and EGFR-overexpressing tumor (4-1ST and CAL27) xenograft models in mice at oral doses of 50 mg/kg and 100 mg/kg.

FUSED HETEROCYCLIC COMPOUND

The present invention provides a compound represented by the formula: wherein R1ais a hydrogen atom, R2a is a C1-6 alkyl group substituted by a group represented by-NR6a-CO-(CH2) n-SO2