147808-42-2Relevant articles and documents
Development of highly potent phosphodiesterase 10A (PDE10A) inhibitors: Synthesis and in vitro evaluation of 1,8-dipyridinyl- and 1-pyridinyl-substituted imidazo[1,5-a ]quinoxalines
Wagner, Sally,Scheunemann, Matthias,Dipper, Karolin,Egerland, Ute,Hoefgen, Norbert,Steinbach, J?rg,Brust, Peter
, p. 97 - 108 (2016)
Herein we report the synthesis of fluorinated inhibitors of phosphodiesterase 10A (PDE10A) which can be used potentially as lead structure for the development of a 18F-labeled PDE10A imaging agent for positron emission tomography. The use of or
NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS
-
Paragraph 0421-0422, (2015/07/27)
The present invention discloses compounds according to Formula I: wherein Cy, R1, L1, R3, R4, R5, La, and Ra are as defined herein. Novel benzimidazoles according to Formula I, a
Discovery of cyclic sulfone hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: Structure-based design and in vivo reduction of amyloid β-peptides
Rueeger, Heinrich,Lueoend, Rainer,Rogel, Olivier,Rondeau, Jean-Michel,M?bitz, Henrik,MacHauer, Rainer,Jacobson, Laura,Staufenbiel, Matthias,Desrayaud, Sandrine,Neumann, Ulf
experimental part, p. 3364 - 3386 (2012/06/01)
Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime- and nonprime-side fragments to a central core template without any amide functionality. The core scaffold selection and the structure-activity relationship development were supported by molecular modeling studies and by X-ray analysis of BACE1 complexes with various ligands to expedite the optimization of the series. The direct extension from P1-aryl- and heteroaryl moieties into the S3 binding pocket allowed the enhancement of potency and selectivity over cathepsin D. Restraining the design and synthesis of compounds to a physicochemical property space consistent with central nervous system drugs led to inhibitors with improved blood-brain barrier permeability. Guided by structure-based optimization, we were able to obtain highly potent compounds such as 60p with enzymatic and cellular IC50 values of 2 and 50 nM, respectively, and with >200-fold selectivity over cathepsin D. Pharmacodynamic studies in APP51/16 transgenic mice at oral doses of 180 μmol/kg demonstrated significant reduction of brain Aβ levels.