- Discovery of N-(3-Carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-2-yl)-lH-pyrazole-5-carboxamide (GLPG1837), a Novel Potentiator Which Can Open Class III Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channels to a High Extent
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Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR). With the discovery of Ivacaftor and Orkambi, it has been shown that CFTR function can be partially restored by administering one or more small molecules. These molecules aim at either enhancing the amount of CFTR on the cell surface (correctors) or at improving the gating function of the CFTR channel (potentiators). Here we describe the discovery of a novel potentiator GLPG1837, which shows enhanced efficacy on CFTR mutants harboring class III mutations compared to Ivacaftor, the first marketed potentiator. The optimization of potency, efficacy, and pharmacokinetic profile will be described.
- Van Der Plas, Steven E.,Kelgtermans, Hans,De Munck, Tom,Martina, Sébastien L. X.,Dropsit, Sébastien,Quinton, Evelyne,De Blieck, Ann,Joannesse, Caroline,Tomaskovic, Linda,Jans, Mia,Christophe, Thierry,Van Der Aar, Ellen,Borgonovi, Monica,Nelles, Luc,Gees, Maarten,Stouten, Pieter,Van Der Schueren, Jan,Mammoliti, Oscar,Conrath, Katja,Andrews, Martin
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- SUBSTITUTED IMIDAZOLES AS N-TYPE CALCIUM CHANNEL BLOCKERS
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Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein R1, R2, R3, and G are defined herein.
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Page/Page column 52
(2015/02/25)
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- SUBSTITUTED IMIDAZOLES AS N-TYPE CALCIUM CHANNEL BLOCKERS
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Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein R1, R2, R3, and G are defined herein.
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Paragraph 0320; 0321
(2015/02/25)
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- NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF CYSTIC FIBROSIS
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The present invention discloses compounds according to Formula I: wherein R1 is as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment cystic fibrosis by administering a compound of the invention.
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Paragraph 0700-0701
(2015/02/25)
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- THIENO[2,3-C]PYRANS AS CFTR MODULATORS
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The present invention discloses compounds according to Formula I: Wherein R is as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment cystic fibrosis by administering a compound of the invention.
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Paragraph 00207
(2015/02/25)
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- TETRAHYDROPYRAN-4-YLETHYLAMINO- OR TETRAHYDROPYRANYL-4-ETHYLOXY-PYRIMIDINES OR -PYRIDAZINES AS ISOPRENYLCYSTEINCARBOXYMETHYL TRANSFERASE INHIBITORS
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A compound of formula (I): wherein: R1 is selected from: (i) phenyl, optionally substituted by one fluoro group; (ii) thienyl; (iii) furanyl; (iv) C1-4 alkyl; and (v) H; R2 is selected from: (II), R3 is selected from: (III), X is selected from NH and O; R4 is selected from phenyl, a 5-membered heteroaryl or a 6-membered heteroaryl, all of which are optionally substituted by one or more substituents selected from the group consisting of: methyl, methoxy, trifluoromethyl, trifluoromethoxy, cyano, fluoro, -OC2H4OMe, and pyrazolyl.
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Page/Page column 31
(2014/04/03)
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- NOVEL 4-(HETEROCYCLOALKYL)BENZENE-1,3-DIOL COMPOUNDS AS TYROSINASE INHIBITORS, PROCESS FOR THE PREPARATION THEREOF AND USE THEREOF IN HUMAN MEDICINE AND ALSO IN COSMETICS
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The present invention relates to novel 4- (heterocycloalkyl) benzene- 1,3-diol compounds corresponding to general formula (I) below: to the compositions containing same, to the process for the preparation thereof and to the use thereof in pharmaceutical or cosmetic compositions for use in the treatment or prevention of pigmentary disorders
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Page/Page column 23-24
(2010/06/20)
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- An efficient protocol for the oxidative hydrolysis of ketone SAMP hydrazones employing SeO2 and H2O2 under buffered (pH 7) conditions
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An effective oxidative protocol for the liberation of ketones from SAMP hydrazones employing peroxyselenous acid under aqueous buffered conditions (pH 7) has been developed. The procedure proceeds without epimerization of adjacent stereocenters or dehydration, in representative SAMP alkylation and aldol reaction adducts, respectively.
- Smith III, Amos B.,Liu, Zhuqing,Simov, Vladimir
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experimental part
p. 3131 - 3134
(2010/03/24)
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- CHEMICAL COMPOUNDS
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The present invention relates to novel compounds with a variety of therapeutic uses, more particularly novel substituted cyclic alkylidene compounds that are particularly useful for selective estrogen receptor modulation.
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Page/Page column 68
(2008/06/13)
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- Synthesis of the ABCD-rings of the insecticidal indole alkaloid nodulisporic acid
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Lewis acid mediated cyclization of the aldehyde 7 leads to 8, 9 and 10, of which 10 contains the structural and stereochemical elements of the ABC-rings of nodulisporic acid 1.
- Magnus, Philip,Mansley, Tamsin E.
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p. 6909 - 6912
(2007/10/03)
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