Discovery of 2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide derivatives as new RORγ inhibitors using virtual screening, synthesis and biological evaluation

Zhang, Yan; Xue, Xiaochang; Jin, Xiangyu; Song, Yu; Li, Jing; Luo, Xiaoyu; Song, Ming; Yan, Weiqun; Song, Hong-Rui; Xu, Yong

doi:10.1016/j.ejmech.2014.03.065

Cited by 38 publications

(39 citation statements)

References 24 publications

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“…Using Ni-chelating acceptor beads and streptavidin-coated donor bead pairs from PerkinElmer, a his-tag fusion NR protein and biotinylated coregulator peptides, we also found some NR modulators. These ligands include a PPARγ agonist [61] , an orphan receptor RORγ antagonist [62] , and natural compounds as agonists for the orphan receptors TR4 and COUP-TFII [63,64] .…”

Section: Alphascreen Assaymentioning

confidence: 99%

“…Readers are encouraged to refer to the excellent reviews by Jiang et al for various computational drug design methods [80,81] . Virtual screening has been widely used for the discovery of NR ligands [62,[82][83][84][85] .…”

Section: Virtual Screening Approachesmentioning

confidence: 99%

“…The derivatives demonstrated remarkably improved activity. The most potent was compound 40, which showed an IC 50 value of 50 nmol/L in a GAL4-driven luciferase reporter assay [62] .…”

Section: Discovery Of Ror Modulatorsmentioning

confidence: 99%

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ROR nuclear receptors: structures, related diseases, and drug discovery

et al. 2014

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Nuclear receptors (NRs) are ligand-regulated transcription factors that regulate metabolism, development and immunity. The NR superfamily is one of the major classes of drug targets for human diseases. Retinoic acid receptor-related orphan receptor (ROR) α, β and γ belong to the NR superfamily, and these receptors are still considered as 'orphan' receptors because the identification of their endogenous ligands has been controversial. Recent studies have demonstrated that these receptors are regulated by synthetic ligands, thus emerge as important drug targets for the treatment of multiple sclerosis, rheumatoid arthritis, psoriasis, etc. Studying the structural basis and ligand development of RORs will pave the way for a better understanding of the roles of these receptors in human diseases. Here, we review the structural basis, disease relevance, strategies for ligand identification, and current status of development of therapeutic ligands for RORs.

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Section: Alphascreen Assaymentioning

confidence: 99%

Section: Virtual Screening Approachesmentioning

confidence: 99%

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ROR nuclear receptors: structures, related diseases, and drug discovery

et al. 2014

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“…Recent studies indicate that the modulation of IL-17 levels in autoimmune diseases may be beneficial in treating diseases, including multiple sclerosis, psoriasis, rheumatoid arthritis and inflammatory bowel disease. Thus, RORc is a promising therapeutic target for the treatment of Th17mediated autoimmune diseases [10,11] .…”

Section: Original Articlementioning

confidence: 99%

“…Transient transfection assays were performed as described previously [11,24] . 293T cells were maintained in DMEM containing 10% fetal bovine serum (FBS).…”

Section: Transient Transfection Assaysmentioning

confidence: 99%

Discovery and structural optimization of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-ones as RORc inverse agonists

Wang

Xing

et al. 2016

Acta Pharmacol Sin

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Rhodium‐Catalyzed Asymmetric Hydrogenation of 3‐Benzoylaminocoumarins for the Synthesis of Chiral 3‐Amino Dihydrocoumarins

Liu

Zhou

et al. 2021

Angewandte Chemie

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An asymmetric hydrogenation of 3-benzoylaminocoumarins was achieved for the first time using our Bridge-Phos-Rh catalytic system, providing chiral 3-amino dihydrocoumarins in high yields (up to 98 %) and with excellent enantioselectivities (up to 99.7 % ee). The relationship between the enantioselectivities of the hydrogenations and the dihedral angles and the resulting p-p stacking effects of the BridgePhos-Rh complexes, which were determined by X-ray diffraction analysis, are discussed. The corresponding hydrogenated products allow for many transformations, providing several chiral skeletons with important physiological and pharmacological activities.Scheme 1. Asymmetric hydrogenation of a-dehydroamino acids.

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Discovery of 2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide derivatives as new RORγ inhibitors using virtual screening, synthesis and biological evaluation

Cited by 38 publications

References 24 publications

ROR nuclear receptors: structures, related diseases, and drug discovery

ROR nuclear receptors: structures, related diseases, and drug discovery

Discovery and structural optimization of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-ones as RORc inverse agonists

Rhodium‐Catalyzed Asymmetric Hydrogenation of 3‐Benzoylaminocoumarins for the Synthesis of Chiral 3‐Amino Dihydrocoumarins

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