- Isomeric thiazole derivatives as ligands for the neuropeptide Y5 receptor
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Sets of isomeric thiazole derivatives 1 and 2 have been synthesised in a parallel iterative solution-phase synthesis approach guided by the SAR analysis derived from biological results and computer-aided design and analysis. This synergistic and streamlined working procedure led to highly active isomeric NPY5 receptor ligands. However, a 10-fold difference at least in their respective binding affinities was consistently found for all isomeric pairs 1 and 2. The analysis of conformational differences due to heteroatom interactions in 1 and 2 revealed a favourable C=O...S interaction in 1, whereas thiazoles 2 showed a repulsive C=O...N interaction.
- Nettekoven, Matthias,Guba, Wolfgang,Neidhart, Werner,Mattei, Patrizio,Pflieger, Philippe,Roche, Olivier,Taylor, Sven
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p. 3446 - 3449
(2007/10/03)
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- THIAZOLE DERIVATIVES
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Compounds of formula I are provided as well as pharmaceutically acceptable salts and esters thereof, wherein R1 to R5, n, m and A have the significance disclosed in the specification, and can be used for the treatment or prevention of arthritis, cardiovascular diseases, diabetes, renal failure, eating disorders and obesity.
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