1369959-01-2

Upstream product

• 1369959-19-2 methyl 7-(3,4-dichlorophenyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-carboxylate 
• 1369959-20-5 4-tert-butyl-6-methyl-7-(3,4-dichlorophenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine-4,6(7H)-dicarboxylate 
• 1369959-21-6 (R)-4-tert-butyl-6-methyl-7-(3 ,4-dichlorophenyl)-2, 5-dimethylpyrazolo[1,5-a]pyrimidine-4,6(7H)-dicarboxylate 
• 6287-38-3 3,4-dichlorobenzaldehyde 

Downstream Products

• 1369959-23-8 (R)-tertbutyl-7-(3,4-dichlorophenyl)-6-((S)-2-(4-fluorophenyl)pyrrolidine-1-carbonyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine-4(7H)-carboxylate 
• 1369958-94-0 ((R)-7-(3,4-dichlorophenyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)((S)-2-(3-methylisoxazol-5-yl)pyrrolidin-1-yl)methanone 
• 1431142-39-0 C₂₇H₃₂Cl₂N₆O₂ 
• 1431142-38-9 C₂₅H₂₈Cl₂N₆O₂ 
• 1427301-16-3 C₂₃H₂₀Cl₂N₆ 
• 1427301-15-2 C₂₃H₂₀Cl₂N₆ 
• 1431139-83-1 C₂₈H₂₈Cl₂N₆O₂ 
• 1427301-14-1 C₂₂H₁₇Cl₂FN₆ 
• 1427300-80-8 C₂₃H₂₀Cl₂N₆ 
• 1427300-73-9 C₂₀H₂₂Cl₂N₄O₃ 
• 1427300-98-8 C₂₂H₂₄Cl₂N₆ 
• 1427300-97-7 C₂₀H₂₀Cl₂N₆ 
• 1427301-19-6 C₂₃H₂₀Cl₂N₆O 
• 1427301-18-5 C₂₃H₂₀Cl₂N₆O 

Relevant academic research and scientific papers

Triazolo and imidazo dihydropyrazolopyrimidine potassium channel antagonists

Previously disclosed C6 amido and benzimidazole dihydropyrazolopyrimidines were potent and selective blockers of IKur current. Syntheses and SAR for C6 triazolo and imidazo dihydropyrazolopyrimidines series are described. Trifluoromethylcyclohexyl N(1) triazole, compound 51, was identified as a potent and selective Kv1.5 inhibitor with an acceptable PK and liability profile.

Discovery of ((S)-5-(methoxymethyl)-7-(1-methyl-1 H -indol-2-yl)-2- (trifluoromethyl)-4,7-dihydropyrazolo[1,5- a ]pyrimidin-6-yl)((S)-2-(3- methylisoxazol-5-yl)pyrrolidin-1-yl)methanone as a potent and selective I Kur inhibitor

Previously disclosed dihydropyrazolopyrimidines are potent and selective blockers of IKur current. A potential liability with this chemotype is the formation of a reactive metabolite which demonstrated covalent binding to protein in vitro. When substituted at the 2 or 3 position, this template yielded potent IKur inhibitors, with selectivity over hERG which did not form reactive metabolites. Subsequent optimization for potency and PK properties lead to the discovery of ((S)-5-(methoxymethyl)-7-(1-methyl-1H-indol- 2-yl)-2-(trifluoromethyl)-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)((S) -2-(3-methylisoxazol-5-yl)pyrrolidin-1-yl)methanone (13j), with an acceptable PK profile in preclinical species and potent efficacy in the preclinical rabbit atrial effective refractory period (AERP) model.