- RADIOLABELED DARAPLADIB AND ANALOGS THEREOF AND THEIR USE AS IMAGING COMPOUNDS
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The present inventors have developed new radiolabeled Darapladib and analogs thereof which can be used for the specific detection of vulnerable atherosclerotic plaques by targeting lipoprotein-associated phospholipase A2 (Lp-PLA2) which is a biomarker of
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- Regioselectivity of thiouracil alkylation: Application to optimization of Darapladib synthesis
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Darapladib is one of the most potent Lp-PLA2 (Lipoprotein-associated phospholipase A2) inhibitor with an IC50 of 0.25 nM. We demonstrate that a crucial step of Darapladib synthesis was not correctly described in the litera
- Guibbal, Florian,Bénard, Sébastien,Patché, Jessica,Meneyrol, Vincent,Couprie, Jo?l,Yong-Sang, Jennyfer,Meilhac, Olivier,Jestin, Emmanuelle
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p. 787 - 792
(2018/01/17)
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- Compounds
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Pyrimidone compounds of formula (I): are inhibitors of the enzyme Lp-PLA2 and are of use in treating atherosclerosis.
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Page/Page column 41; 42
(2016/05/11)
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- PROCESSES FOR THE PREPARATION OF DARAPLADIB AND ITS INTERMEDIATES
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The present invention provides a process for the preparation of ethyl {2-[(4- fluorobenzyl)sulfanyl]-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl}acetate of Formula 4, {2-[(4-fluorobenzyl)sulfanyl]-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta [d]pyri
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- Selective inhibitors and tailored activity probes for lipoprotein- associated phospholipase A2
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Lipoprotein-associated phospholipase A2 (Lp-PLA2 or PLA2G7) binds to low-density lipoprotein (LDL) particles, where it is thought to hydrolyze oxidatively truncated phospholipids. Lp-PLA2 has also been implicate
- Nagano, Joseph M.G.,Hsu, Ku-Lung,Whitby, Landon R.,Niphakis, Micah J.,Speers, Anna E.,Brown, Steven J.,Spicer, Timothy,Fernandez-Vega, Virneliz,Ferguson, Jill,Hodder, Peter,Srinivasan, Prabhavathi,Gonzalez, Tara D.,Rosen, Hugh,Bahnson, Brian J.,Cravatt, Benjamin F.
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p. 839 - 843
(2013/02/25)
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- NOVEL PROCESSES
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This invention relates to methods of making a compound of formula (I) and intermediates for same. The compounds of formula (I) being useful for treating cardiovascular and inflammatory diseases such as atherosclerosis.
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- METHODS OF TREATMENT AND PREVENTION OF NEURODEGENERATIVE DISEASES AND DISORDERS
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The present invention provides compostions and methods useful for treating and preventing neurodegenerative disease and neurologically related disorders by inhibition of Lp-PLA2. The compositions and methods are useful for treating and preventing diseases
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- METHODS OF TREATMENT AND PREVENTION OF METABOLIC BONE DISEASES AND DISORDERS
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The present invention provides compostions and methods useful for treating and preventing metabolic bone diseases and disorders by inhibition of Lp-PLA2. The compositions and methods are useful for treating and preventing metabolic bone disease
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- The identification of clinical candidate SB-480848: A potent inhibitor of lipoprotein-associated phospholipase A2
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Modification of the pyrimidone 5-substituent in clinical candidate SB-435495 has given a series of inhibitors of recombinant lipoprotein-associated phospholipase A2 with sub-nanomolar potency. Cyclopentyl fused derivative 21, SB-480848, showed an enhanced in vitro and in vivo profile versus SB-435495 and has been selected for progression to man.
- Blackie, Josie A.,Bloomer, Jackie C.,Brown, Murray J. B.,Cheng, Hung-Yuan,Hammond, Beverley,Hickey, Deirdre M. B.,Ife, Robert J.,Leach, Colin A.,Lewis, V. Ann,Macphee, Colin H.,Milliner, Kevin J.,Moores, Kitty E.,Pinto, Ivan L.,Smith, Stephen A.,Stansfield, Ian G.,Stanway, Steven J.,Taylor, Maxine A.,Theobald, Colin J.
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p. 1067 - 1070
(2007/10/03)
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- Novel compounds
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Pyrimidone compounds of formula (I): are inhibitors of the enzyme Lp-PLA2 and are of use in treating atheroscelerosis.
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