- THYROID HORMONE RECEPTOR BETA AGONIST COMPOUNDS
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Provided herein are compounds, preferably thyroid hormone receptor beta (THR beta) agonist compounds, compositions thereof, and methods of their preparation, and methods of agonizing THR beta and methods for treating disorders mediated by THR beta.
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- THYROID HORMONE RECEPTOR BETA AGONIST COMPOUNDS
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Provided herein are compounds, preferably thyroid hormone receptor beta (THR beta) agonist compounds, compositions thereof, methods of their preparation, and methods of agonizing THR beta and methods for treating disorders mediated by THR beta.
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- POLYCYCLIC COMPOUNDS AS ROR-GAMMA MODULATORS
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The present invention provides compounds which are modulators of RORγ and their use for the treatment of diseases or conditions mediated by RORγ. Further, the present invention relates to processes of preparing such compounds, their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, methods for using such compounds and pharmaceutical compositions containing them.
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- CYCLOPROPYL DERIVATIVES AS ROR-GAMMA MODULATORS
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The present invention provides compounds which are modulators of RORγ and their use for the treatment of diseases or conditions mediated by RORγ. Further, the present invention relates to processes of preparing such compounds, their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, methods for using such compounds and pharmaceutical compositions containing them (Formula I).
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- NOVEL COMPOUNDS AS ROR-GAMMA MODULATORS
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The present invention provides compounds which are modulators of ROR? and their use for the treatment of diseases or conditions mediated by ROR?. Further, the present invention relates to processes of preparing such compounds, their tautomeric forms, deuterated form, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, methods for using such compounds and pharmaceutical compositions containing them. formula (I)
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- Discovery of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3- yloxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile (MGL-3196), a highly selective thyroid hormone receptor β agonist in clinical trials for the treatment of dyslipidemia
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The beneficial effects of thyroid hormone (TH) on lipid levels are primarily due to its action at the thyroid hormone receptor β (THR-β) in the liver, while adverse effects, including cardiac effects, are mediated by thyroid hormone receptor α (THR-α). A pyridazinone series has been identified that is significantly more THR-β selective than earlier analogues. Optimization of this series by the addition of a cyanoazauracil substituent improved both the potency and selectivity and led to MGL-3196 (53), which is 28-fold selective for THR-β over THR-α in a functional assay. Compound 53 showed outstanding safety in a rat heart model and was efficacious in a preclinical model at doses that showed no impact on the central thyroid axis. In reported studies in healthy volunteers, 53 exhibited an excellent safety profile and decreased LDL cholesterol (LDL-C) and triglycerides (TG) at once daily oral doses of 50 mg or higher given for 2 weeks.
- Kelly, Martha J.,Pietranico-Cole, Sherrie,Larigan, J. Douglas,Haynes, Nancy-Ellen,Reynolds, Charles H.,Scott, Nathan,Vermeulen, John,Dvorozniak, Mark,Conde-Knape, Karin,Huang, Kuo-Sen,So, Sung-Sau,Thakkar, Kshitij,Qian, Yimin,Banner, Bruce,Mennona, Frank,Danzi, Sara,Klein, Irwin,Taub, Rebecca,Tilley, Jefferson
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p. 3912 - 3923
(2014/06/09)
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- NOVEL BENZAMIDE DERIVATIVES AS MODULATORS OF THE FOLLICLE STIMULATING HORMONE
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The present invention provides new compounds of formula I, wherein Q, R1, R2, R4, R5, R6, Xi, R7, R8, M and G1 nare defined as in formula I; invention compounds are modulators of follicle-stimulating hormone - ("FSH") which are useful for male and female contraception as well as other disorders modulated by FSH receptor.
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Page/Page column 147-148
(2008/12/04)
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- COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS
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The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the Abl, BCR-Abl, CSK, JNK1, JNK2, PDGF-R, p38, p70S6K, TGF beta , SRC, EGFR, c-Kit, trkB, FGFR3, Fes, Lck, Syk, RAF, MKK4, MKK6 and SAPK2 beta kinases.
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Page/Page column 28
(2008/06/13)
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- Synthesis and biological evaluation of 1,2,4- triazinylphenylalkylthiazolecarboxylic acid esters as cytokine-inhibiting antedrugs with strong bronchodilating effects in an animal model of asthma
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The influx of leukocytes (eosinophils, lymphocytes, and monocytes) into the airways and their production of proinflammatory cytokines contribute to the severity of allergic asthma. We describe here the synthesis and pharmacological evaluation of a series
- Freyne, Eddy J.,Lacrampe, Jean F.,Deroose, Frederik,Boeckx, Gustaaf M.,Willems, Marc,Embrechts, Werner,Coesemans, Erwin,Willems, Johan J.,Fortin, Jerome M.,Ligney, Yannick,Dillen, Lieve L.,Cools, Willy F.,Goossens, Jan,Corens, David,De Groot, Alex,Van Wauwe, Jean P.
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p. 2167 - 2175
(2007/10/03)
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