343246-71-9Relevant academic research and scientific papers
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
Finlay, Heather J.,Lloyd, John,Vaccaro, Wayne,Kover, Alexander,Yan, Lin,Bhave, Gauri,Prol, Joseph,Huynh, Tram,Bhandaru, Rao,Caringal, Yolanda,Dimarco, John,Gan, Jinping,Harper, Tim,Huang, Christine,Conder, Mary Lee,Sun, Huabin,Levesque, Paul,Blanar, Michael,Atwal, Karnail,Wexler, Ruth
, p. 3036 - 3048 (2012/06/01)
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.
Dihydropyrazolopyrimidines containing benzimidazoles as KV1.5 potassium channel antagonists
Lloyd, John,Finlay, Heather J.,Atwal, Karnail,Kover, Alexander,Prol, Joseph,Yan, Lin,Bhandaru, Rao,Vaccaro, Wayne,Huynh, Tram,Huang, Christine S.,Conder, MaryLee,Jenkins-West, Tonya,Sun, Huabin,Li, Danshi,Levesque, Paul
scheme or table, p. 5469 - 5473 (2010/05/19)
Dihydropyrazolopyrimidines with a C6 heterocycle substituent were found to have high potency for block of KV1.5. Investigation of the substitution in the benzimidazole ring and the substituent in the 5-position of the dihydropyrazolopyrimidine
