Structural highlights
Function
[RORG_HUMAN] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock.
Publication Abstract from PubMed
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 (RORgammat). 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.
3-Substituted Quinolines as RORgammat Inverse Agonists.,Tanis VM, Venkatesan H, Cummings MD, Albers M, Kent Barbay J, Herman K, Kummer DA, Milligan C, Nelen MI, Nishimura R, Schlueter T, Scott B, Spurlino J, Wolin R, Woods C, Xue X, Edwards JP, Fourie AM, Leonard K Bioorg Med Chem Lett. 2019 Jun 15;29(12):1463-1470. doi:, 10.1016/j.bmcl.2019.04.021. Epub 2019 Apr 12. PMID:31010722[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tanis VM, Venkatesan H, Cummings MD, Albers M, Kent Barbay J, Herman K, Kummer DA, Milligan C, Nelen MI, Nishimura R, Schlueter T, Scott B, Spurlino J, Wolin R, Woods C, Xue X, Edwards JP, Fourie AM, Leonard K. 3-Substituted Quinolines as RORgammat Inverse Agonists. Bioorg Med Chem Lett. 2019 Jun 15;29(12):1463-1470. doi:, 10.1016/j.bmcl.2019.04.021. Epub 2019 Apr 12. PMID:31010722 doi:http://dx.doi.org/10.1016/j.bmcl.2019.04.021
