1431473-05-0Relevant articles and documents
Investigation of orexin-2 selective receptor antagonists: Structural modifications resulting in dual orexin receptor antagonists
Skudlarek, Jason W.,DiMarco, Christina N.,Babaoglu, Kerim,Roecker, Anthony J.,Bruno, Joseph G.,Pausch, Mark A.,O'Brien, Julie A.,Cabalu, Tamara D.,Stevens, Joanne,Brunner, Joseph,Tannenbaum, Pamela L.,Wuelfing, W. Peter,Garson, Susan L.,Fox, Steven V.,Savitz, Alan T.,Harrell, Charles M.,Gotter, Anthony L.,Winrow, Christopher J.,Renger, John J.,Kuduk, Scott D.,Coleman, Paul J.
, p. 1364 - 1370 (2017/03/08)
In an ongoing effort to explore the use of orexin receptor antagonists for the treatment of insomnia, dual orexin receptor antagonists (DORAs) were structurally modified, resulting in compounds selective for the OX2R subtype and culminating in the discovery of 23, a highly potent, OX2R-selective molecule that exhibited a promising in vivo profile. Further structural modification led to an unexpected restoration of OX1R antagonism. Herein, these changes are discussed and a rationale for selectivity based on computational modeling is proposed.
Identification of MK-8133: An orexin-2 selective receptor antagonist with favorable development properties
Kuduk, Scott D.,Skudlarek, Jason W.,Dimarco, Christina N.,Bruno, Joseph G.,Pausch, Mark H.,O'brien, Julie A.,Cabalu, Tamara D.,Stevens, Joanne,Brunner, Joseph,Tannenbaum, Pamela L.,Garson, Susan L.,Savitz, Alan T.,Harrell, Charles M.,Gotter, Anthony L.,Winrow, Christopher J.,Renger, John J.,Coleman, Paul J.
, p. 2488 - 2492 (2015/06/02)
Abstract Antagonism of orexin receptors has shown clinical efficacy as a novel paradigm for the treatment of insomnia and related disorders. Herein, molecules related to the dual orexin receptor antagonist filorexant were transformed into compounds that w
2-PYRIDYLOXY-3-ESTER-4-ETHER OREXIN RECEPTOR ANTAGONISTS
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, (2015/06/25)
The present invention is directed to 2-pyridyloxy-3-ester-4-ether compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the 2-pyridyloxy-4-ether compounds described herein in the potential treatment or prev
PIPERIDINYLOXY LACTONE OREXIN RECEPTOR ANTAGONISTS
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, (2015/07/07)
The present invention is directed to piperidinyloxy lactone compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the piperidinyloxy lactone compounds described herein in the potential treatment or preventi
2-PYRIDYLOXY-3-ESTER-4-NITRILE OREXIN RECEPTOR ANTAGONISTS
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, (2014/05/07)
The present invention is directed to 2-pyridyloxy-3-ester-4-nitrile compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the 2-pyridyloxy-3-ester-4-nitrile compounds described herein in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
2-PYRIDYLOXY-4-ESTER OREXIN RECEPTOR ANTAGONISTS
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, (2014/07/08)
The present invention is directed to 2-pyridyloxy-4-ester compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the 2-pyridyloxy-4-ester compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
2-PYRIDYLOXY-4-ETHER OREXIN RECEPTOR ANTAGONISTS
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, (2014/09/29)
The present invention is directed to 2-pyridyloxy-4-ether compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the 2-pyridyloxy-4-ether compounds described herein in the potential treatment or prevention o
2-HYDROXYMETHYL-SUBSTITUTED OREXIN RECEPTOR ANTAGONISTS
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, (2014/11/13)
The present invention is directed to 2-hydroxymethyl compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
2-PYRIDYLOXY-3-SUBSTITUTED-4-NITRILE OREXIN RECEPTOR ANTAGONISTS
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, (2014/05/24)
The present invention is directed to 2-pyridyloxy-3-substituted-4-nitrile compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the 2-pyridyloxy-3-substituted-4-nitrile compounds described herein in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
HALO AND TRIFLUOROMETHYL SUBSTITUTED OREXIN RECEPTOR ANTAGONISTS
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, (2014/11/13)
The present invention is directed to halo and trifluoromethyl substituted compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.