- Boron-Containing Small Molecules as Anti-Inflammatory Agents
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Compounds and methods of treating anti-inflammatory conditions are disclosed.
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Paragraph 0722-0723
(2015/11/16)
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- Identification of (R)-6-(1-(4-cyano-3-methylphenyl)-5-cyclopentyl-4,5- dihydro-1H-pyrazol-3-yl)-2-methoxynicotinic acid, a highly potent and selective nonsteroidal mineralocorticoid receptor antagonist
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A novel series of nonsteroidal mineralocorticoid receptor (MR) antagonists identified as part of our strategy to follow up on the clinical candidate PF-03882845 (2) is reported. Optimization departed from the previously described pyrazoline 3a and focused on improving the selectivity for MR versus the progesterone receptor (PR) as an approach to avoid potential sex-hormone-related adverse effects and improving biopharmaceutical properties. From this effort, (R)-14c was identified as a potent nonsteroidal MR antagonist (IC50 = 4.5 nM) with higher than 500-fold selectivity versus PR and other related nuclear hormone receptors, with improved solubility as compared to 2 and pharmacokinetic properties suitable for oral administration. (R)-14c was evaluated in vivo using the increase of urinary Na+/K+ ratio in rat as a mechanism biomarker of MR antagonism. Treatment with (R)-14c by oral administration resulted in significant increases in urinary Na +/K+ ratio and demonstrated this novel compound acts as an MR antagonist.
- Casimiro-Garcia, Agustin,Piotrowski, David W.,Ambler, Catherine,Arhancet, Graciela B.,Banker, Mary Ellen,Banks, Tereece,Boustany-Kari, Carine M.,Cai, Cuiman,Chen, Xiangyang,Eudy, Rena,Hepworth, David,Hulford, Catherine A.,Jennings, Sandra M.,Loria, Paula M.,Meyers, Marvin J.,Petersen, Donna N.,Raheja, Neil K.,Sammons, Matthew,She, Li,Song, Kun,Vrieze, Derek,Wei, Liuqing
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p. 4273 - 4288
(2014/06/09)
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- 4, 5-DIHYDRO-LH-PYRAZOLE COMPOUNDS AND THEIR PHARMACEUTICAL USES
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Mineralocorticoid receptor antagonists (MRa), pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, diabetic nephropathy and hypertension in mammals, including humans.
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Page/Page column 65
(2010/11/03)
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- 2,4'-BIPYRIDINYL COMPOUNDS AS PROTEIN KINASE D INHIBITORS USEFUL FOR THE TREATMENT OF IA HEART FAILURE AND CANCER
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The present invention provides novel organic compounds of Formula I: methods of use, and pharmaceutical compositions thereof.
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Page/Page column 134
(2010/01/07)
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- NEW PYRIDINE ANALOGUES VIII 518
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The present invention relates to certain new pyridin analogues of Formula ( I ) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.
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Page/Page column 184-185
(2008/12/07)
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- New Pyridine Analogues IX 519
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The present invention relates to certain new pyridin analogues of Formula (I) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.
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Page/Page column 39-40
(2008/12/06)
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- 2-AMINOBENZAMIDE DERIVATIVE
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To provide a novel and excellent agent for treating or preventing nociceptive pain, neuropathic pain, cancer pain, headache, bladder function disorder and the like, based on the inhibitory action on the capsaicin receptor VR1 activation. The present inven
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Page/Page column 20
(2008/12/07)
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- Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same
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Compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, traumatic injury, and others.
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Page/Page column 38-39
(2008/06/13)
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- AZAINDOLE DERIVATIVES AS INHIBITORS OF P38 KINASE
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The invention is directed to methods to inhibit p38 kinase, preferably p38-α using compounds which are azaindoles wherein the azaindoles are coupled through an azacyclic linker to another cyclic moiety.
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Page/Page column 66-67
(2010/11/24)
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- Diels-Alder reactions of 6-alkyl-3,5-dichloro-2H-1,4-oxazin-2-ones with alkynes: Synthesis of 3,5-disubstituted 2,6-dichloropyridines
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The Diels-Alder reactiion of 6-alkyl-3,5-dichloro-2H-1,4-oxazin-2-ones 1 with different types of acetylenic compounds 2 is shown to be a versatile method for the generation of variously substituted 2,6-dichloropyridines. In most cases a high degree of reg
- Meerpoel,Deroover,Van Aken,Lux,Hoornaert
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p. 765 - 768
(2007/10/02)
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- GENERATION OF SPECIFICALLY SUBSTITUTED PYRIDINES AND PYRIDONES FROM 2(1H) PYRAZINONES AND ACETYLENES: A FMO DESCRIPTION
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The title compounds were obtained from reaction of variously substituted 2(1H)pyrazinones with acetylenic derivatives.Experimental evidence points out to a two step mechanism: a Diels Alder cycloaddition followed by immediate decomposition of the adducts
- Tutonda, M.,Vanderzande, D.,Hendrickx, M.,Hoornaert, G.
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p. 5715 - 5732
(2007/10/02)
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