ACS Medicinal Chemistry Letters · 2015 · 58 citations · 9 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryLead OptimizationHit-to-lead OptimizationLipophilicity OptimizationPotency OptimizationReceptor PharmacologyReproductive PharmacologySelectivity Optimization5-Hydroxytryptamine 3 Receptor AntagonistsHormone Receptor PharmacologyLipophilic Efficiency AnalysisLipophilic Ligand EfficiencyReceptor Binding OptimizationSex Hormone Pharmacology
Further lead optimization on N-acyl-triazolopiperazine antagonists to the neurokinin-3 receptor (NK3R) based on the concurrent improvement in bioactivity and ligand lipophilic efficiency (LLE) is reported. Overall, compound 3 (LLE > 6) emerged as the most efficacious in castrated rat and monkey to lower plasma LH, and it displayed the best off-target safety profile that led to its clinical candidate nomination for the treatment of sex-hormone disorders.
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Predicting plasma protein binding of drugs: a new approach
Nicole A. Kratochwil, Walter Huber, Francis Müller et al. · Biochemical Pharmacology · 2002 · 550 citations