1188143-94-3Relevant articles and documents
Discovery and Optimization of 1-Phenoxy-2-aminoindanes as Potent, Selective, and Orally Bioavailable Inhibitors of the Na+/H+ Exchanger Type 3 (NHE3)
Rackelmann, Nils,Matter, Hans,Englert, Heinrich,Follmann, Markus,Maier, Thomas,Weston, John,Arndt, Petra,Heyse, Winfried,Mertsch, Katharina,Wirth, Klaus,Bialy, Laurent
, p. 8812 - 8829 (2016/10/22)
The design, synthesis, and structure-activity relationship of 1-phenoxy-2-aminoindanes as inhibitors of the Na+/H+ exchanger type 3 (NHE3) are described based on a hit from high-throughput screening (HTS). The chemical optimization resulted in the discovery of potent, selective, and orally bioavailable NHE3 inhibitors with 13d as best compound, showing high in vitro permeability and lacking CYP2D6 inhibition as main optimization parameters. Aligning 1-phenoxy-2-aminoindanes onto the X-ray structure of 13d then provided 3D-QSAR models for NHE3 inhibition capturing guidelines for optimization. These models showed good correlation coefficients and allowed for activity estimation. In silico ADMET models for Caco-2 permeability and CYP2D6 inhibition were also successfully applied for this series. Moreover, docking into the CYP2D6 X-ray structure provided a reliable alignment for 3D-QSAR models. Finally 13d, renamed as SAR197, was characterized in vitro and by in vivo pharmacokinetic (PK) and pharmacological studies to unveil its potential for reduction of obstructive sleep apneas.
A Pd(II)-catalyzed ring-expansion reaction of cyclic 2-azidoalcohol derivatives: Synthesis of azaheterocycles
Chiba, Shunsuke,Xu, Yan-Jun,Wang, Yi-Feng
supporting information; experimental part, p. 12886 - 12887 (2009/12/06)
(Chemical Equation Presented) A Pd(II)-catalyzed ring expansion-reaction of cyclic 2-azidoalcohol derivatives was found to proceed via an unprecedented C-C bond cleavage-C-N bond formation sequence, providing substituted azaheterocycles.
