- 1-(2-hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile derivatives as potent and tissue selective androgen receptor modulators
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We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.
- Chekler, Eugene L. Piatnitski,Unwalla, Rayomond,Khan, Taukeer A.,Tangirala, Raghuram S.,Johnson, Mark,St. Andre, Michael,Anderson, James T.,Kenney, Thomas,Chiparri, Sue,McNally, Chris,Kilbourne, Edward,Thompson, Catherine,Nagpal, Sunil,Weber, Gregory,Schelling, Scott,Owens, Jane,Morris, Carl A.,Powell, Dennis,Verhoest, Patrick R.,Gilbert, Adam M.
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supporting information
p. 2462 - 2471
(2014/04/17)
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- An efficient synthesis of 4-chloro-2-pyrrolino[2,3- d ]pyrimidin-6-one and its 7-substituted analogues
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An efficient synthesis of 4-chloro-2-pyrrolino[2,3-d]pyrimidin-6-one was achieved in four steps starting from dimethyl malonate in 23% overall yield. This synthesis was demonstrated on 100 g scale to obtain 4-chloro-2-pyrrolino[2, 3-d]pyrimidin-6-one in 9
- Vaid, Radhe K.,Spitler, Jeremy T.,Boini, Sathish,May, Scott A.,Hoying, Richard C.
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p. 2396 - 2400
(2012/10/08)
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- BICYCLIC HETEROCYCLE DERIVATIVES AND THEIR USE AS GPCR MODULATORS
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The present invention relates to Bicyclic Heterocycle Derivatives of Formula (I), compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a diabetic
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Page/Page column 55
(2010/04/03)
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- AKT AND P70 S6 KINASE INHIBITORS
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The present invention provides AKT and p70 S6 kinase inhibitors of the formula: The present invention also provides pharmaceutical compositions comprising compounds of Formula I, uses of compounds of Formula I and methods of using compounds of Formula I.
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Page/Page column 24
(2010/06/11)
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- AKT PROTEIN KINASE INHIBITORS
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The present invention provides compounds, including resolved enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof, comprising the Formula: A-L-CR where CR is a cyclical core group, L is a linking group and A is as defined herein. Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.
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- α-pyrimidinyl acrylic acid derivatives
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The invention discloses compounds of formula I STR1 the use of such compounds for the control of phytopathogens, composition for facilitating such use, and the preparation of the compounds of formula I.
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