- Non-steroidal dissociated glucocorticoid agonists: Indoles as A-ring mimetics and function-regulating pharmacophores
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We report a SAR of non-steroidal glucocorticoid mimetics that utilize indoles as A-ring mimetics. Detailed SAR is discussed with a focus on improving PR and MR selectivity, GR agonism, and in vitro dissociation profile. SAR analysis led to compound (R)-33 which showed high PR and MR selectivity, potent agonist activity, and reduced transactivation activity in the MMTV and aromatase assays. The compound is equipotent to prednisolone in the LPS-TNF model of inflammation. In mouse CIA, at 30 mg/kg compound (R)-33 inhibited disease progression with an efficacy similar to the 3 mg/kg dose of prednisolone.
- Betageri, Raj,Gilmore, Thomas,Kuzmich, Daniel,Kirrane, Thomas M.,Bentzien, J?rg,Wiedenmayer, Dieter,Bekkali, Younes,Regan, John,Berry, Angela,Latli, Bachir,Kukulka, Alison J.,Fadra, Tazmeen N.,Nelson, Richard M.,Goldrick, Susan,Zuvela-Jelaska, Ljiljana,Souza, Don,Pelletier, Josephine,Dinallo, Roger,Panzenbeck, Mark,Torcellini, Carol,Lee, Heewon,Pack, Edward,Harcken, Christian,Nabozny, Gerald,Thomson, David S.
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scheme or table
p. 6842 - 6851
(2011/12/22)
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- PIPERIDINONES USEFUL IN THE TREATMENT OF INFLAMMATION
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There is provided compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, m and n have meanings given in the description, and pharmaceutically acceptable derivatives thereof, which compounds are useful in the treatment of diseases and conditions associated with inflammation.
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Page/Page column 106
(2008/12/07)
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- Hydroxylation of Nitroarenes with Alkyl Hydroperoxide Anions via Vicarious Nucleophilic Substitution of Hydrogen
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Rhone-Poulenc Polska Ltd., ul. Grzybowska 80/82, 00-844 Warszawa, Poland Garbo- and heterocyclic nitroarenes react with anions of tert-butyl and cumyl hydroperoxides in the presence of strong bases to form substituted o- and p-nitrophenols. The reaction usually proceeds in high yields and is of practical value as a method of synthesis and manufacturing of nitrophenols. Orientation of the hydroxylation can be controlled to a substantial extent by selection of the proper conditions. Basic mechanistic features of this process were clarified.
- Makosza, Mieczyslaw,Sienkiewicz, Krzysztof
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p. 4199 - 4208
(2007/10/03)
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