- Design, synthesis, and SAR of new pyrrole-oxindole progesterone receptor modulators leading to 5-(7-fluoro-3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)- 1-methyl-1H-pyrrole-2-carbonitrile (WAY-255348)
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We have continued to explore the 3,3-dialkyl-5-aryloxindole series of progesterone receptor (PR) modulators looking for new agents to be used in female healthcare: contraception, fibroids, endometriosis, and certain breast cancers. Previously we reported
- Fensome, Andrew,Adams, William R.,Adams, Andrea L.,Berrodin, Tom J.,Cohen, Jeff,Huselton, Christine,Illenberger, Arthur,Kern, Jeffrey C.,Hudak, Valerie A.,Marella, Michael A.,Melenski, Edward G.,McComas, Casey C.,Mugford, Cheryl A.,Slayden, Ov D.,Yudt, Matthew,Zhang, Zhiming,Zhang, Puwen,Zhu, Yuan,Winneker, Richard C.,Wrobel, Jay E.
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p. 1861 - 1873
(2008/12/20)
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- Process for the preparation of indolin-2-one derivatives useful as PR modulators
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Processes for dialkylating indolinones, specifically indolin-2-ones are provided. The processes for dialkylating an indolin-2-one include performing the dialkylation in the presence of at least 2 equivalents of a first base, a second base containing at le
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Page/Page column 19
(2010/11/30)
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- Progesterone receptor antagonists, contraceptive regimens, and kits
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A method of contraception is provided which involves delivery of 21 to 27 consecutive days of one or more PR antagonists in the absence of a progestin, estrogen, or other steroidal compound, followed by 1 to 7 days without any active agent. Also described is a pharmaceutically useful kit to facilitate delivery of this regimen.
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Page/Page column 10
(2010/02/15)
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- 4,5-pyrazinoxindoles
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Disclosed are novel 4,5-pyrazinoxindoles having the formula These compounds inhibit or modulate protein kinases, in particular JNK protein kinases. These compounds and their pharmaceutically acceptable salts, and prodrugs of said compounds, are useful as anti-inflammatory agents, particularly useful in the treatment of rheumatoid arthritis. Also disclosed are pharmaceutical compositions containing such compounds, and methods for the treatment and/or control of inflammation, particularly in the treatment or control of rheumatoid arthritis, using these compounds.
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- 4,5-azolo-oxindoles
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Disclosed are novel 4,5-azolo-oxindoles having the formula These compounds inhibit cyclin-dependent kinases (CDKs), in particular CDK2. Thus, these compounds and their pharmaceutically acceptable salts, and prodrugs of said compounds, are anti-proliferative agents useful in the treatment or control of cell proliferative disorders, in particular cancer. Also disclosed are pharmaceutical compositions containing these compounds, and methods for the treatment and/or prevention of cancer, particularly in the treatment or control of solid tumors using these compounds, as well as intermediates useful in the preparation of compounds of formula I.
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- Preparation of indoles and oxindoles from N-(tert-butoxycarbonyl)-2-alkylanilines
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Treatment of dilithiated N-(tert-butoxycarbonyl)anilines 1 with dimethylformamide or carbon dioxide furnishes intermediates 3, 5, that are easily converted to N-(tert-butoxycarbonyl)indoles 4 and oxindoles (indol-2(3H)-ones, 7), respectively. Condensation of dilithiated 1 with N-methoxy-N-methylamides provides ketones 9 which are cyclized upon trifluoroacetic acid treatment to either 2-substituted 1-(tert-butoxycarbonyl)indoles 10 or 2-substituted indoles 11 depending on the reaction time. This general methodology has been applied to efficient synthesis of 1,2-alkyl-bridged indoles 12, 1,3,4,5-tetrahydrobenz[c,d]indole (16), 2a,3,4,5-tetrahydrobenz[c,d]indol-2(1H)-one (18), and 1-(tert-butoxycarbonyl)1H-pyrrolo[2,3-b]pyridine (21).
- Clark,Muchowski,Fisher,Flippin,Repke,Souchet
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p. 871 - 878
(2007/10/02)
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