106868-33-1Relevant academic research and scientific papers
Discovery of (R)-1-(3-((2-Chloro-4-(((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-5-methoxyphenyl)amino)-3-oxopropyl)piperidin-4-yl [1,1′-biphenyl]-2-ylcarbamate (TD-5959, GSK961081, Batefenterol): First-in-Class dual pharmacology multivalent muscarinic antagonist and β2 agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD)
Hughes, Adam D.,Chen, Yan,Hegde, Sharath S.,Jasper, Jeffrey R.,Jaw-Tsai, Sarah,Lee, Tae-Weon,McNamara, Alexander,Pulido-Rios, M. Teresa,Steinfeld, Tod,Mammen, Mathai
, p. 2609 - 2622 (2015/04/14)
Through application of our multivalent approach to drug discovery we previously reported the first discovery of dual pharmacology MABA bronchodilators, exemplified by 1. Herein we describe the subsequent lead optimization of both muscarinic antagonist and β2 agonist activities, through modification of the linker motif, to achieve 24 h duration of action in a guinea pig bronchoprotection model. Concomitantly we targeted high lung selectivities, low systemic exposures and identified crystalline forms suitable for inhalation devices. This article culminates with the discovery of our first clinical candidate 12f (TD-5959, GSK961081, batefenterol). In a phase 2b trial, batefenterol produced statistical and clinically significant differences compared to placebo and numerically greater improvements in the primary end point of trough FEV1 compared to salmeterol after 4 weeks of dosing in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
NOVEL BENZAMIDE COMPOUNDS FOR USE IN MCH RECEPTOR RELATED DISORDERS
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Page 31-32, (2008/06/13)
Novel compounds of Formula I which modulate MCH activity are disclosed, in which A is a linker, Ar, is an aryl or heteroaryl group; R1 is hydrogen or a lower alkoxy group; Q together with the carbonyl forms an amide group, which is further substituted with an amine group; R5 is hydrogen, halogen atoms, alkoxy groups, hydroxy, alkylamino groups, dialkylamino groups, hydroxylalkyl groups, carboxamido groups, acylamido groups, acyl groups,-CHO, nitrile, alkyl, alkenyl or alkynyl groups,-SCH3, partially or fully fluorinated alkyl, alkoxy or thioalkoxy groups such as-CH2CF3,-CF2CF3,-CF3,-OCF3,-SCF3;-SO2NH2,-SO2NHAlk,-SO2NAlk2,-SO2AIk; R8 is hydrogen, halogen atoms, alkyl, alkenyl or alkynyl groups, cycloalkyl groups, alkylcycloalkyl groups, alkoxy groups, dialkylamino groups,-CONHAIk,-CONAIk2,-NHCO-Alk,-CO-Alk,-SCH3, partially or fully fluorinated alkyl, alkoxy or thioalkoxy groups such as-CH2CF3,-CF2CF3,-CF3,-OCF3,-SCF3; X is H, F, Cl, Br, I,-SCH3, partially or fully fluorinated alkyl, alkoxy or thioalkoxy groups such as-CH2CF3,-CF2CF3,-CF3,-OCF3,-SCF3; OCH3 or lower alkyl or alkenyl group; and which are useful in the treatment or prevention of e.g. obesity, depression, diabetes, bulimia etc.
NOVEL METHOXYBENZAMIDE COMPOUNDS FOR USE IN MCH RECEPTOR RELATED DISORDERS
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Page/Page column 55-56, (2010/02/07)
Novel compounds of Formula (I) which modulate MCH activity are disclosed, in which A is a linker; Ar1 is an aryl or heteroaryl group; R1 is a lower alkoxy group; R2 is an R1 group or hydrogen, an OH or an NH2 group, Q together with the carbonyl forms an amide group, which is further substituted with an amine group; R5 is selected from hydrogen, halogen atoms, alkoxy groups, hydroxy, alkylamino groups, dialkylamino groups, hydroxylalkyl groups, carboxamido groups, acylamido groups, acyl groups, -CHO, nitrile, alkyl, alkenyl or alkynyl groups, -SCH3, partially or fully fluorinated alkyl, alkoxy or thioalkoxy groups such as -CH2CF3, -CF2CF3, -CF3, -OCF3, -SCF3; -SO2NH2, -SO2NHAlk, -SO2NAlk2, -SO2Alk; X is H, F, Cl, Br, I, -SCH3, -CF3, -OCF3, -SCF3, OCH3, or lower alkyl or alkenyl group; R8 is halogen atoms, alkyl, alkenyl or alkynyl groups, cycloalkyl groups, aryl groups, heteroaryl groups, heterocyclyl groups, alkylcycloalkyl groups, alkylaryl groups, alkylheterocyclyl groups, alkylheteroaryl groups, arylalkoxy groups, aryloxy groups, alkoxy groups, dialkylamino groups, -CONHAlk, -CONHAr, -CONAlk2, -NHCO-Alk, -NHCO-Ar, -CO-Alk, -CO-Ar, -SCH3, partially or fully fluorinated alkyl, alkoxy or thioalkoxy groups; or R8 is R6-Ar2-B-, in which B is a single bond or a connecting moiety; Ar2 is an Ar1 group; R6 is an R5 group; and which are useful in the treatment or prevention of e.g. obesity, depression, diabetes, bulimia etc.
Pyrrolidinyl and pyrrolinyl ethylamine compounds as kappa agonists
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, (2008/06/13)
A compound of the following formula: and the salts thereof wherein A is hydrogen, halo, or hydroxy, broken line represents an optional double bond with proviso that if the broken line is a double bond, then A is absent; Ar1is optionally substituted phenyl; Ar2is aryl or heteroaryl selected from phenyl, napththyl, or pyridyl, the aryl or heteroaryl being optionally substituted; R1is hydrogen, hydroxy, or C1-C4alkyl; and R2and R3are independently selected from optionally substituted C1-C7alkyl, C3-C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, or R2and R3, together with the nitrogen atom to which they are attached, form an optionally substituted pyrrolidine. These compounds are useful as kappa agonists.
Transition Metal Diene Complexes on Organic Synthesis. Part-17. Studies directed towards the Iron-mediated Synthesis of 2-Oxygenated Carbazole Alkaloids
Knoelker, Hans-Joachim,Bauermeister, Michael
, p. 345 - 354 (2007/10/02)
We described some studies directed towards the synthesis of 2-oxygenated carbazole alkaloids by iron-mediated oxidative coupling of 1,3-cyclohexadiene and the corresponding 3-oxygenated arylamine derivative.The process involves a consecutive formation of a carbon-carbon bond via electrophilic aromatic substitution with an iron-complexed cyclohexadienylium cation and subsequent carbon-nitrogen bond formation via oxidative cyclisation.Using this methodology a synthesis of the biogenetically important alkaloid 2-methoxy-3-methylcarbazole is described.
