147402-52-6Relevant 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.
Pyrrolidine amides of pyrazolodihydropyrimidines as potent and selective KV1.5 blockers
Lloyd, John,Finlay, Heather J.,Vacarro, Wayne,Hyunh, Tram,Kover, Alexander,Bhandaru, Rao,Yan, Lin,Atwal, Karnail,Conder, Mary Lee,Jenkins-West, Tonya,Shi, Hong,Huang, Christine,Li, Danshi,Sun, Huabin,Levesque, Paul
scheme or table, p. 1436 - 1439 (2010/07/02)
Design and synthesis of pyrazolodihydropyrimidines as KV1.5 blockers led to the discovery of 7d as a potent and selective antagonist. This compound showed atrial selective prolongation of effective refractory period in rabbits and was selected for clinical development.
4-(PYRAZOL-3-YLAMINO) PYRIMIDINE DERIVATIVES FOR USE IN THE TREATMENT OF CANCER
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Page/Page column 206-207, (2008/06/13)
A compound of Formula (I); wherein the substituents are as defined in the text for use in modulating insulin-like growth factor 1 receptor activity in a warm blooded animal such as man.
Hydroboration-azide alkylation as efficient tandem reactions for the synthesis of chiral non racemic substituted pyrrolidines
Salmon, Anne,Carboni, Bertrand
, p. 31 - 37 (2007/10/03)
The synthesis of chiral non racemic substituted pyrrolidines from homoallylic alcohols is presented. These precursors are readily converted via the azides to the corresponding pyrrolidines using hydroboration-cycloalkylation tandem reactions as key steps.
Synthesis and 11C-labelling of two selective high affinity nicotinic cholinergic agonists for evaluation as radioligands for PET studies
Dolle, Frederic,Dolci, Lilian,Valette, Heric,Bottlaender, Michel,Fournier, Denis,Fuseau, Chantai,Vaufrey, Francoise,Crouzel, Christian
, p. 1099 - 1112 (2007/10/03)
ABT-418 ((S)-3-methyl-5-[1-methyl-2-pyrrolidinyl]isoxazole) and N-methylcytisine (N-methyl- 1,2,3,4,5,6-hexahydro-1,5-methano-8H-pyrido-[1,2-a][1,5]diazocin-8-one) are two high affinity nicotinic cholinergic agonists. ABT-418 was synthesized in 7 steps from commercially available (S)-Boc- proline in 35% overall yield. Methylation of commercial cytisine cleanly gave N-methyl-cytisine. ABT-418 and N-methylcytisine were labelled using [11C]methyl iodide by methylation of the corresponding nor-precursors for their in vivo evaluation as positron emission tomography (PET) probes of the nicotinic cholinergic receptors in baboon brain. As for [11C]nicotine, specific binding in vivo could not be demonstrated for ABT-418. Therefore, further experiments are needed to determine the full PET pharmacological profile and the subsequent potential clinical applications of ABT-418 as a tracer for PET experiments. For labelled N-methyl-cytisine, radioactivity in the cerebral cortex and in tile blood were similar. Thus, 11C-labelled N-methylcytisine does not appear to be a suitable ligand for mapping brain nAChR.
Ligands for brain cholinergic channel receptors: Synthesis and in vitro characterization of novel isoxazoles and isothiazoles as bioisosteric replacements for the pyridine ring in nicotine
Garvey,Wasicak,Elliott,Lebold,Hettinger,Carrera,Lin,He,Holladay,Anderson,Cadman,Raszkiewicz,Sullivan,Arneric
, p. 4455 - 4463 (2007/10/02)
Ligands which activate neuronal nicotinic acetylcholine receptors (nAChRs) represent a potential approach for the palliative treatment for the symptoms of memory loss associated with Alzheimer's disease (AD). Based upon this approach, a series of novel 3,
