Optimizing Ligand Efficiency of Selective Androgen Receptor Modulators (SARMs)
| Autor: | Anthony L. Handlon, Lisa M. Leesnitzer, Joseph Wendell Wilson, Rodolfo Cadilla, Philip Stewart Turnbull, Chuck Poole, Raymond V. Merrihew, Lee T. Schaller, John C. Ulrich |
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| Rok vydání: | 2015 |
| Předmět: |
Ligand efficiency
Trifluoromethyl 010405 organic chemistry Stereochemistry Organic Chemistry 010402 general chemistry 01 natural sciences Biochemistry 0104 chemical sciences Bioavailability Androgen receptor chemistry.chemical_compound chemistry Selective androgen receptor modulator Benzyl alcohol Drug Discovery Potency Solubility |
| Zdroj: | ACS Medicinal Chemistry Letters. 7:83-88 |
| ISSN: | 1948-5875 |
| Popis: | A series of selective androgen receptor modulators (SARMs) containing the 1-(trifluoromethyl)benzyl alcohol core have been optimized for androgen receptor (AR) potency and drug-like properties. We have taken advantage of the lipophilic ligand efficiency (LLE) parameter as a guide to interpret the effect of structural changes on AR activity. Over the course of optimization efforts the LLE increased over 3 log units leading to a SARM 43 with nanomolar potency, good aqueous kinetic solubility (>700 μM), and high oral bioavailability in rats (83%). |
| Databáze: | OpenAIRE |
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