202134-57-4Relevant articles and documents
Structure-based Discovery of Phenyl (3-Phenylpyrrolidin-3-yl)sulfones as Selective, Orally Active RORγt Inverse Agonists
Duan, James J.-W.,Lu, Zhonghui,Jiang, Bin,Stachura, Sylwia,Weigelt, Carolyn A.,Sack, John S.,Khan, Javed,Ruzanov, Max,Galella, Michael A.,Wu, Dauh-Rurng,Yarde, Melissa,Shen, Ding-Ren,Shuster, David J.,Borowski, Virna,Xie, Jenny H.,Zhang, Lisa,Vanteru, Sridhar,Gupta, Arun Kumar,Mathur, Arvind,Zhao, Qihong,Foster, William,Salter-Cid, Luisa M.,Carter, Percy H.,Dhar, T. G. Murali
supporting information, p. 367 - 373 (2019/03/21)
A new phenyl (3-phenylpyrrolidin-3-yl)sulfone series of RORγt inverse agonists was discovered utilizing the binding conformation of previously reported bicyclic sulfonamide 1. Through a combination of structure-based design and structure-activity relationship studies, a polar set of amides at N1-position of the pyrrolidine ring and perfluoroisopropyl group at para-position of the 3-phenyl group were identified as critical structural elements to achieve high selectivity against PXR, LXRα, and LXRβ. Further optimization led to the discovery of (1R,4r)-4-((R)-3-((4-fluorophenyl)sulfonyl)-3-(4-(perfluoropropan-2-yl)phenyl)pyrrolidine-1-carbonyl)cyclohexane-1-carboxylic acid (26), which displayed excellent selectivity, desirable liability and pharmacokinetic properties in vitro, and a good pharmacokinetic profile in mouse. Oral administration of 26 demonstrated dose-dependent inhibition of IL-17 production in a mouse IL-2/IL-23-induced pharmacodynamic model and biologic-like efficacy in an IL-23-induced mouse acanthosis model.
ROR GAMMA MODULATORS
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Page/Page column 101, (2018/05/27)
There are described ROR? modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising th
CARBOCYCLIC SULFONE RORγ MODULATORS
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Page/Page column 52, (2015/07/16)
Described are RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.
HETEROCYCLIC SULFONE AS ROR-GAMMA MODULATORS
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Page/Page column 39-40, (2015/07/16)
Described are RORγ modulators of the formula (I), [INSERT CHEMICAL STRUCTURE HERE] or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.
PYRROLIDINYL SULFONE RORGAMMA MODULATORS
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Paragraph 0281-0282, (2015/07/15)
Described are RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.
ROR MODULATORS AND THEIR USES
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Paragraph 0085, (2013/11/19)
The invention relates to ROR modulators; compositions comprising an effective amount of a ROR modulator; and methods for treating or preventing diseases associated with ROR.
ROR MODULATORS AND THEIR USES
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Paragraph 0080; 0081, (2013/11/05)
The invention relates to ROR modulators; compositions comprising an effective amount of a ROR modulator; and methods for treating or preventing diseases associated with ROR. The invention is based in part on the discovery of ROR modulators which interact with RORa and/or RORy and thereby inhibit or induce RORa and/or RORy-activity, and RORa- and/or RORy-regulated target gene and protein expression.
ROR MODULATORS AND THEIR USES
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Paragraph 0090 - 0092, (2013/11/19)
The invention relates to ROR modulators; compositions comprising an effective amount of a ROR modulator; and methods for treating or preventing diseases associated with ROR.
N- (1, 1, 1, 3, 3, 3-HEXAFLUORO-2-HYDROXYPROPAN-2-YL) BENZYL-N' -ARYLCARBONYLPIPERAZ INE DERIVATIVES
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Page/Page column 25, (2009/12/23)
101 Abstract. The present invention relates tohexafluoroisopropanol derivativeshaving the general formula I X O N N Y OH F 3 C CF 3 A R 1 R 2 R 3 ( ) n W Z B R 6 5 Formula I to pharmaceutical compositions comprising the same and to the use of these hexafluoroisopropanol derivatives inthe treatment of atherosclerosis
Design and synthesis of heterocyclic malonyl-CoA decarboxylase inhibitors
Cheng, Jie-Fei,Chen, Mi,Liu, Bin,Hou, Zheng,Arrhenius, Thomas,Nadzan, Alex M.
, p. 695 - 700 (2007/10/03)
We have previously reported the discovery of small molecule inhibitors of malonyl-CoA decarboxylase (MCD) as novel metabolic modulators, which inhibited fatty acid oxidation and consequently increased the glucose oxidation rates in the isolated working ra