Related Experiment Video
Updated: Aug 17, 2026

Modeling Ligands into Maps Derived from Electron Cryomicroscopy
Published on: July 19, 2024
Isomeric thiazole derivatives as ligands for the neuropeptide Y5 receptor
Matthias Nettekoven1, Wolfgang Guba, Werner Neidhart
1F. Hoffmann-La Roche Ltd, Pharmaceutical Research Basel, Discovery Chemistry, CH-4070 Basel, Switzerland. matthias.nettekoven@roche.com
Abstract:
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.
Related Concept Videos
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
The direct-acting...
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Cholinergic Antagonists: Chemistry and Structure-Activity Relationship
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
Indirect-Acting Cholinergic Agonists: Pharmacological Actions
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
