3-Substituted Quinolines as RORγt Inverse Agonists
| Autor: | Maxwell D. Cummings, Thomas Schlueter, David A. Kummer, J. Kent Barbay, Krystal Herman, Craig R. Woods, John Spurlino, Kristi A. Leonard, Cynthia M. Milligan, Hariharan Venkatesan, Rachel Nishimura, Michael Albers, Ronald L. Wolin, James P. Edwards, Marina I. Nelen, Xiaohua Xue, Anne M. Fourie, Virginia M. Tanis, Brian Scott |
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| Rok vydání: | 2019 |
| Předmět: |
Drug Inverse Agonism
Clinical Biochemistry Heteroatom Retinoic acid Pharmaceutical Science 01 natural sciences Biochemistry chemistry.chemical_compound Structure-Activity Relationship RAR-related orphan receptor gamma Drug Discovery Inverse agonist Molecule Animals Humans Solubility Molecular Biology Orphan receptor Improved solubility Molecular Structure 010405 organic chemistry Organic Chemistry Combinatorial chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry Quinolines Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 29(12) |
| ISSN: | 1464-3405 |
| Popis: | We have previously reported the syntheses of a series of 3,6-disubstituted quinolines as modulators of the retinoic acid receptor-related orphan receptor gamma t (RORγt). These molecules are potent binders but are high molecular weight and they exhibited poor solubility at pH 2 and pH 7. This manuscript details our efforts at improving physical chemical properties for this series of compounds by increasing the diversity at the 3-position (i.e. introducing heteroatoms and lowering the molecular weight). These efforts have led to molecules which are potent binders with improved solubility. |
| Databáze: | OpenAIRE |
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