170012-71-2Relevant articles and documents
Tricyclic-Carbocyclic RORγt Inverse Agonists - Discovery of BMS-986313
Yang, Michael G.,Beaudoin-Bertrand, Myra,Xiao, Zili,Marcoux, David,Weigelt, Carolyn A.,Yip, Shiuhang,Wu, Dauh-Rurng,Ruzanov, Max,Sack, John S.,Wang, Jinhong,Yarde, Melissa,Li, Sha,Shuster, David J.,Xie, Jenny H.,Sherry, Tara,Obermeier, Mary T.,Fura, Aberra,Stefanski, Kevin,Cornelius, Georgia,Khandelwal, Purnima,Karmakar, Ananta,Basha, Mushkin,Babu, Venkatesh,Gupta, Arun Kumar,Mathur, Arvind,Salter-Cid, Luisa,Denton, Rex,Zhao, Qihong,Dhar, T. G. Murali
, p. 2714 - 2724 (2021)
SAR efforts directed at identifying RORγt inverse agonists structurally different from our clinical compound 1 (BMS-986251) led to tricyclic-carbocyclic analogues represented by 3-7 and culminated in the identification of 3d (BMS-986313), with structural differences distinct from 1. The X-ray co-crystal structure of 3d with the ligand binding domain of RORγt revealed several key interactions, which are different from 1. The in vitro and in vivo PK profiles of 3d are described. In addition, we demonstrate robust efficacy of 3d in two preclinical models of psoriasis - the IMQ-induced skin lesion model and the IL-23-induced acanthosis model. The efficacy seen with 3d in these models is comparable to the results observed with 1.
TRICYCLIC SULFONES AS ROR GAMMA MODULATORS
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Paragraph 0413-0414, (2018/05/24)
There are described 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.
EXCITATORY AMINO ACID RECEPTOR ANTAGONISTS
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, (2008/06/13)
The present invention provides novel compounds that affect excitatory amino acid receptors and are useful in the treatment of neurological disorders. This invention also provides synthetic methods for the preparation of the novel compounds.
