1221500-75-9

Upstream product

• 943994-02-3 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one 
• 1221502-74-4 4-bromo-5-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol 
• 1221502-73-3 5-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazole 
• 64287-17-8 1-(2,4-Difluoro-phenyl)-butane-1,3-dione 
• 364-83-0 2',4'-difluoroacetophenone 

Relevant academic research and scientific papers

Discovery of 6-[5-(4-fluorophenyl)-3-methyl-pyrazol-4-yl]-benzoxazin-3-one derivatives as novel selective nonsteroidal mineralocorticoid receptor antagonists

In the course of our study on selective nonsteroidal mineralocorticoid receptor (MR) antagonists, a series of novel benzoxazine derivatives possessing an azole ring as the core scaffold was designed for the purpose of attenuating the partial agonistic activity of the previously reported dihydropyrrol-2-one derivatives. Screening of alternative azole rings identified 1,3-dimethyl pyrazole 6a as a lead compound with reduced partial agonistic activity. Subsequent replacement of the 1-methyl group of the pyrazole ring with larger lipophilic side chains or polar side chains targeting Arg817 and Gln776 increased MR binding activity while maintaining the agonistic response at the lower level. Among these compounds, 6-[1-(2,2-difluoro-3-hydroxypropyl)-5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]-2H-1,4-benzoxazin-3(4H)-one (37a) showed highly potent in vitro activity, high selectivity versus other steroid hormone receptors, and good pharmacokinetic profiles. Oral administration of 37a in deoxycorticosterone acetate-salt hypertensive rats showed a significant blood pressure-lowering effect with no signs of antiandrogenic effects.

PYRAZOLE COMPOUNDS

The present invention relates to wherein each symbol is as defined in the specification. The compound has a superior mineralocorticoid receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of a disease or condition mediated by the mineralocorticoid receptor activation.