- Optimization of drug-like properties of nonsteroidal glucocorticoid mimetics and identification of a clinical candidate
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A series of nonsteroidal dissociated glucocorticoid receptor agonists was optimized for drug-like properties such as cytochrome P450 inhibition, metabolic stability, aqueous solubility, and hERG ion channel inhibition. This effort culminated in the identification of the clinical candidate compound (R)-39.
- Harcken, Christian,Riether, Doris,Liu, Pingrong,Razavi, Hossein,Patel, Usha,Lee, Thomas,Bosanac, Todd,Ward, Yancey,Ralph, Mark,Chen, Zhidong,Souza, Donald,Nelson, Richard M.,Kukulka, Alison,Fadra-Khan, Tazmeen N.,Zuvela-Jelaska, Ljiljana,Patel, Mita,Thomson, David S.,Nabozny, Gerald H.
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supporting information
p. 1318 - 1323
(2015/01/09)
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- Identification of highly efficacious glucocorticoid receptor agonists with a potential for reduced clinical bone side effects
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Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain "diazaindole" moieties and display different transcriptional regulatory profiles in vitro and are
- Harcken, Christian,Riether, Doris,Kuzmich, Daniel,Liu, Pingrong,Betageri, Raj,Ralph, Mark,Emmanuel, Michel,Reeves, Jonathan T.,Berry, Angela,Souza, Donald,Nelson, Richard M.,Kukulka, Alison,Fadra, Tazmeen N.,Zuvela-Jelaska, Ljiljana,Dinallo, Roger,Bentzien, J?rg,Nabozny, Gerald H.,Thomson, David S.
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p. 1583 - 1598
(2014/03/21)
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- Nonsteroidal dissociated glucocorticoid agonists containing azaindoles as steroid A-ring mimetics
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Syntheses and structure-activity relationships (SAR) of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain azaindole moieties as A-ring mimetics and display various degrees of in vitro dissociation between gene trans
- Riether, Doris,Harcken, Christian,Razavi, Hossein,Kuzmich, Daniel,Gilmore, Thomas,Bentzien, J?rg,Pack, Edward J.,Souza, Donald,Nelson, Richard M.,Kukulka, Alison,Fadra, Tazmeen N.,Zuvela-Jelaska, Ljiljana,Pelletier, Josephine,Dinallo, Roger,Panzenbeck, Mark,Torcellini, Carol,Nabozny, Gerald H.,Thomson, David S.
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experimental part
p. 6681 - 6698
(2010/12/19)
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- GLUCOCORTICOID MIMETICS, METHODS OF MAKING THEM, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
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Compounds of Formula I wherein R1, R2, X, and Y are as defined herein, or a tautomer, optical isomer, prodrug, co-crystal, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.
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Page/Page column 60-61
(2009/12/28)
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- Identification of dissociated non-steroidal glucocorticoid receptor agonists
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A new series of ligands for the glucocorticoid receptor (GR) is described. SAR development was guided by docking 3 into the GR active site and optimizing an unsubstituted phenyl ring for key interactions found in the steroid A-ring binding pocket. To iden
- Kuzmich, Daniel,Kirrane, Tom,Proudfoot, John,Bekkali, Younes,Zindell, Renee,Beck, Laura,Nelson, Richard,Shih, Cheng-Kon,Kukulka, Alison J.,Paw, Zofia,Reilly, Patty,Deleon, Rodney,Cardozo, Mario,Nabozny, Gerald,Thomson, David
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p. 5025 - 5031
(2008/02/11)
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- Quinol-4-ones as steroid A-ring mimetics in nonsteroidal dissociated glucocorticoid agonists
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We report on the nuclear receptor binding affinities, cellular activities of transrepression and transactivation, and anti-inflammatory properties of a quinol-4-one and other A-ring mimetic containing nonsteroidal class of glucocorticoid agonists.
- Regan, John,Lee, Thomas W.,Zindell, Renée M.,Bekkali, Younes,Bentzien, J?rg,Gilmore, Thomas,Hammach, Abdelhakim,Kirrane, Thomas M.,Kukulka, Alison J.,Kuzmich, Daniel,Nelson, Richard M.,Proudfoot, John R.,Ralph, Mark,Pelletier, Josephine,Souza, Donald,Zuvela-Jelaska, Lijiljana,Nabozny, Gerald,Thomson, David S.
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p. 7887 - 7896
(2007/10/03)
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- Stereoselective synthesis of certain trifluoromethyl-substituted alcohols
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A process for stereoselective synthesis of a compound of Formula (I) wherein R1, R2, R3, R4, and R5 are as described herein.
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Page/Page column 7-8
(2010/02/14)
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- Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
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A compound of Formula (IA) or Formula (IB) wherein R1, R2, R3, R4, R5, R6, R7,and R8 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceu
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-
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- Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
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A compound of Formula (IA) or Formula (IB) wherein R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceu
- -
-
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- GLUCOCORTICOID MIMETICS, METHODS OF MAKING THEM, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
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A compound of Formula (IA) or Formula (IB) wherein R1, R2, R3, R4, R5, R6, R7, and R8 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocortic
- -
-
-
- GLUCOCORTICOID MIMETICS, METHODS OF MAKING THEM, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
-
Compounds of Formula (IA) and Formula (IB) wherein R1, R2, R3, R4, R5, and R6 are as defined herein for Formula (IA) or Formula (IB), or a tautomer, prodrug, solvate,or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.
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Page/Page column 107
(2010/02/07)
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- 4-(ARYL OR HETEROARYL) -2-BUTYLAMINE DERIVATIVES AND THEIR USE AS GLUCOCORTICOID LIGANS
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A compound of Formula (IA) or Formula (IB) wherein R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.
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