- BET INHIBITORS FOR MODULATING DUX4 EXPRESSION IN FSHD
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The present disclosure provides BET inhibitors of the formula: wherein the variables are defined herein, as well as pharmaceutical compositions thereof. The present disclosure also provides methods of treating a patient comprising administering a bromo- and extra-terminal (BET) domain inhibitor for the treatment of FSHD which modulates DUX4 expression. In some embodiments, the present methods comprise using one or more BET inhibitors as a therapeutic agent for the treatment of FSHD patients including patients who are being treated with one or more palliative treatments such as therapy and/or agents which lead to increased muscle mass.
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Page/Page column 272; 273
(2020/07/14)
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- Novel and highly potent histamine H3 receptor ligands. Part 3: An alcohol function to improve the pharmacokinetic profile
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Synthesis and biological evaluation of potent histamine H3 receptor antagonists incorporating a hydroxyl function are described. Compounds in this series exhibited nanomolar binding affinities for human receptor, illustrating a new possible component for the H3 pharmacophore. As demonstrated with compound BP1.4160 (cyclohexanol 19), the introduction of an alcohol function counter-intuitively allowed to reach high in vivo efficiency and favorable pharmacokinetic profile with reduced half-life.
- Labeeuw, Olivier,Levoin, Nicolas,Poupardin-Olivier, Olivia,Calmels, Thierry,Ligneau, Xavier,Berrebi-Bertrand, Isabelle,Robert, Philippe,Lecomte, Jeanne-Marie,Schwartz, Jean-Charles,Capet, Marc
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p. 2548 - 2554
(2013/06/27)
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- Process for the preparation of 3-aroyl-5-aminobenzofuran derivatives
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The present invention relates to a process for the preparation of 3-aroyl-5-aminobenzofuran derivatives useful as antiarrhythmic drugs which avoids the use of nitro intermediates.
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Page/Page column 32
(2012/06/01)
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- PROCESS FOR THE PREPARATION OF 3-AROYL-5-AMINOBENZOFURAN DERIVATIVES
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The present invention relates to a process for the preparation of 3-aroyl -5- aminobenzofuran derivatives useful as antiarrhythmic drugs which avoids the use of nitro intermediates.
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Page/Page column 42
(2012/05/31)
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- Discovery and characterization of 6-{4-[3-(R)-2-methylpyrrolidin-1-yl) propoxy]phenyl}-2H-pyridazin-3-one (CEP-26401, irdabisant): A potent, selective histamine H3 receptor inverse agonist
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Optimization of a novel series of pyridazin-3-one histamine H3 receptor (H3R) antagonists/inverse agonists identified 6-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2H-pyridazin-3-one (8a, CEP-26401; irdabisant) as a lead candid
- Hudkins, Robert L.,Raddatz, Rita,Tao, Ming,Mathiasen, Joanne R.,Aimone, Lisa D.,Becknell, Nadine C.,Prouty, Catherine P.,Knutsen, Lars J. S.,Yazdanian, Mehran,Moachon, Gilbert,Ator, Mark A.,Mallamo, John P.,Marino, Michael J.,Bacon, Edward R.,Williams, Michael
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experimental part
p. 4781 - 4792
(2011/09/21)
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- Novel and highly potent histamine H3 receptor ligands. Part 1: Withdrawing of hERG activity
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Pre-clinical investigation of some aryl-piperidinyl ether histamine H3 receptor antagonists revealed a strong hERG binding. To overcome this issue, we have developed a QSAR model specially dedicated to H3 receptor ligands. This model was designed to be di
- Levoin, Nicolas,Labeeuw, Olivier,Calmels, Thierry,Poupardin-Olivier, Olivia,Berrebi-Bertrand, Isabelle,Lecomte, Jeanne-Marie,Schwartz, Jean-Charles,Capet, Marc
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scheme or table
p. 5378 - 5383
(2011/10/12)
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- COMPOUNDS COMPRISING A LACTAM OR A LACTAM DERIVATIVE MOIETY, PROCESSES FOR MAKING THEM, AND THEIR USES
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The present invention relates to compounds of formula (I) comprising a lactam or a lactam derivative moiety, processes for preparing them, pharmaceutical compositions comprising said compounds and their uses as pharmaceuticals.
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Page/Page column 84
(2008/06/13)
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- Phenoxypropylpiperidines and -pyrrolidines and their use as histamine H3-receptor ligands
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The present patent application concerns compounds of formula (I), with R1 and R2 taken together with the nitrogen atom to which they are attached, form a mono or bicyclic saturated nitrogen-containing ring; their preparation and their use as a H3 receptor ligand for treating e.g. CNS disorders like Alzheimer's disease.
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Page/Page column 41
(2008/06/13)
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- SUBSTITUTED ANILINIC PIPERIDINES AS MCH SELECTIVE ANTAGONISTS
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This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therepeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier.
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Page column 189
(2010/02/06)
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- Aminoalkoxybiphenylnitriles as histamine-3 receptor ligands
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Biaryl nitrile amines were prepared and found to have high affinity and selectivity for human and rat histamine H3 receptors.
- Faghih, Ramin,Dwight, Wesley,Vasudevan, Anil,Dinges, Jurgen,Conner, Scott E.,Esbenshade, Timothy A.,Bennani, Youssef L.,Hancock, Arthur A.
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p. 3077 - 3079
(2007/10/03)
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- Synthesis, Calcium-Channel-Blocking Activity, and Antihypertensive Activity of 4-(Diarylmethyl)-1-piperidines and Structurally Related
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A series of 4-(diarylmethyl)-1-piperidines and structurally related compounds were synthesized as calcium-channel blockers and antihypertensive agents.Compounds were evaluated for calcium-channel-blocking activity by determineng their ability to antagonize calcium-induced contractions of isolated rabbit aortic strips.The most potent compounds were those with fluoro substituents in the 3- and/or 4-positions of both rings of the diphenylmethyl group.Bis(4-fluorophenyl)acetonitrile analogue 79 was similar in potency to bis(4-fluorophenyl)methyl compound 1.The methylene analogue of 1 (78) and derivatives of 1 that contained a hydroxyl (76), carbamoyl (80), amino (81), or acetamido (82) substituent on the methyl group were less potent.In most cases substituents on the phenoxy ring, changes in the distance between the aryloxy group and the piperidine nitrogen, and the substitution of S, N(CH3), or CH2 for the oxygen atom of the aryloxy group had only a small to moderate effect on the potency.The best compounds in this series were more potent than verapamil, diltiazem, flunarizine, and lidoflazine, but were less potent than nifedipine.Compounds were evaluated for antihypertensive activity in spontaneusly hypertensive rats (SHR) at an oral dose of 30 mg/kg.Of the 55 compounds tested, only nine produced a statistically significant (p-1-piperidinyl>propoxy>-3-methoxyphenyl>ethanone (63), which produced a 35percent reduction in blood pressure and was similar in activity to nifedipine.At lower doses, however, 4--1-piperidine (93) was one of the most effective antihypertensive agents, producing reductions in blood pressure of 17 and 11percent at oral doses of 10 and 3 mg/kg, respectively; 63 was inactive at 10 mg/kg.
- Shanklin, James R.,Johnson, Christopher P.,Proakis, Anthony G.,Barrett, Richard J.
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p. 3011 - 3022
(2007/10/02)
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