39497-06-8Relevant articles and documents
A novel class of oral direct renin inhibitors: Highly potent 3,5-disubstituted piperidines bearing a tricyclic P3 - P1 pharmacophore
Ostermann, Nils,Ruedisser, Simon,Ehrhardt, Claus,Breitenstein, Werner,Marzinzik, Andreas,Jacoby, Edgar,Vangrevelinghe, Eric,Ottl, Johannes,Klumpp, Martin,Hartwieg, J. Constanze D.,Cumin, Frederic,Hassiepen, Ulrich,Trappe, J?rg,Sedrani, Richard,Geisse, Sabine,Gerhartz, Bernd,Richert, Paul,Francotte, Eric,Wagner, Trixie,Kr?mer, Markus,Kosaka, Takatoshi,Webb, Randy L.,Rigel, Dean F.,Maibaum, Jürgen,Baeschlin, Daniel K.
, p. 2196 - 2206 (2013/05/22)
A small library of fragments comprising putative recognition motifs for the catalytic dyad of aspartic proteases was generated by in silico similarity searches within the corporate compound deck based on rh-renin active site docking and scoring filters. Subsequent screening by NMR identified the low-affinity hits 3 and 4 as competitive active site binders, which could be shown by X-ray crystallography to bind to the hydrophobic S3-S 1 pocket of rh-renin. As part of a parallel multiple hit-finding approach, the 3,5-disubstituted piperidine (rac)-5 was discovered by HTS using a enzymatic assay. X-ray crystallography demonstrated the eutomer (3S,5R)-5 to be a peptidomimetic inhibitor binding to a nonsubstrate topography of the rh-renin prime site. The design of the potent and selective (3S,5R)-12 bearing a P 3sp-tethered tricyclic P3-P1 pharmacophore derived from 3 is described. (3S,5R)-12 showed oral bioavailability in rats and demonstrated blood pressure lowering activity in the double-transgenic rat model.
MEDICAMENTS FOR INHALATION COMPRISING ANTICHOLINERGICS AND A BETAMIMETIC
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Page/Page column 46; 52, (2008/06/13)
The present invention relates to novel pharmaceutical compositions comprising one or more, preferably one anticholinergic 1 and a betamimetic of formula 2 processes for preparing them and their use in the treatment of respiratory complaints.
Anticholinergics, processes for the preparation thereof, and pharmaceutical compositions
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Page 7, (2010/01/31)
A compound of formula 1 wherein: X? is an anion with a single negative charge; A and B, which are identical or different, are each —O—, —S—, —NH—, —CH2—, —CH═CH—, or —N(C1-C4-alkyl)-; R is hydrogen, hydroxy, —C1-C4-alkyl, —C1-C4-alkyloxy, —C1-C4-alkylene-halogen, —O—C1-C4-alkylene-halogen, —C1-C4-alkylene-OH, —CF3, —CHF2, —C1-C4-alkylene-C1-C4-alkyloxy, —O—COC1-C4-alkyl, —O—COC1-C4-alkylene-halogen, —C1-C4-alkylene-C3-C6-cycloalkyl, —O—COCF3, or halogen; R1 and R2, which are identical or different, are each —C1-C5-alkyl, which is optionally substituted by —C3-C6-cycloalkyl, hydroxy, or halogen, or R1 and R2 together are a —C3-C5-alkylene bridge; R3, R4, R3′, and R4′, which are identical or different, are each hydrogen, C1-C4-alkyl, C1-C4-alkyloxy, hydroxy, —CF3, —CHF2, —CN, —NO2, or halogen; Rx and Rx′, which are identical or different, are each hydrogen, C1-C4-alkyl, C1-C4-alkyloxy, hydroxy, —CF3, —CHF2, —CN, —NO2, or halogen, or Rx and Rx′ together are a single bond or a bridging group selected from —O—, —S—, —NH—, —CH2—, —CH2—CH2—, —N(C1-C4-alkyl)-, —CH(C1-C4-alkyl)-, and —C(C1-C4-alkyl)2-, or a pharmacologically acceptable acid addition salt thereof, processes for preparing, them and their use in pharmaceutical compositions.
