- 1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors: From Hit Generation to Orally Bioavailable Brain Penetrant Leads
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1,4-Oxazines are presented, which show good in vitro inhibition in enzymatic and cellular BACE1 assays. We describe lead optimization focused on reducing the amidine pKa while optimizing interactions in the BACE1 active site. Our strategy permi
- Rombouts, Frederik J. R.,Tresadern, Gary,Delgado, Oscar,Martínez-Lamenca, Carolina,Van Gool, Michiel,García-Molina, Aránzazu,Alonso De Diego, Sergio A.,Oehlrich, Daniel,Prokopcova, Hana,Alonso, José Manuel,Austin, Nigel,Borghys, Herman,Van Brandt, Sven,Surkyn, Michel,De Cleyn, Michel,Vos, Ann,Alexander, Richard,Macdonald, Gregor,Moechars, Dieder,Gijsen, Harrie,Trabanco, Andrés A.
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p. 8216 - 8235
(2015/11/09)
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- 5-ARYL-1-IMINO-1-OXO-[1,2,4]THIADIAZINES
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The present invention provides a compound of formula I' having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are
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- 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 (“mGluR2”), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
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Paragraph 0156; 0157
(2013/10/07)
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- 5-AMINO[1,4]THIAZINES AS BACE 1 INHIBITORS
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The present invention provides a compound of formula I having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.
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- 3-AMINO-5,6-DIHYDRO-1H-PYRAZIN-2-ONE DERIVATIVES USEFUL FOR THE TREATMENT OF ALZHEIMER'S DISEASE AND OTHER FORMS OF DEMENTIA
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The present invention relates to novel 3-amino-5,6-dihydro-1H-pyrazin-2-one derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical com
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Paragraph 0137; 0138
(2013/05/08)
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- 1,4 OXAZINES AS BACE1 AND/OR BACE2 INHIBITORS
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The present invention provides 1,4 Oxazines of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present
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Page/Page column 36
(2012/08/08)
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- 1,4 OXAZINES AS BACE1 AND/OR BACE2 INHIBITORS
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The present invention relates to 1,4 Oxazines of formula I having BACE 1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the prese
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Page/Page column 31
(2012/07/28)
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- 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 ("mGluR2"), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
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Page/Page column 39
(2012/05/31)
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- 1,4 OXAZINES AS BACE1 AND/OR BACE2 INHIBITORS
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The present invention relates to 1,4 Oxazines of formula (I): having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the pre
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- 3-AMINO-5,6-DIHYDRO-1H-PYRAZIN-2-ONE DERIVATIVES USEFUL FOR THE TREATMENT OF ALZHEIMER?S DISEASE AND OTHER FORMS OF DEMENTIA
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The present invention relates to novel 3-amino-5,6-dihydro-1H-pyrazin-2-one derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical com
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Page/Page column 32
(2012/01/14)
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- PYRAZINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF NEUROLOGICAL DISORDERS
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The invention relates to novel heterocyclic compounds of the formula (I) in which all of the variables are as defined in the specification, in free form or in salt form, to their preparation, to their medical use and to medicaments comprising them.
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- Rational design and synthesis of aminopiperazinones as β-secretase (BACE) inhibitors
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Aminopiperazinone inhibitors of BACE were identified by rational design. Structure based design guided idea prioritization and initial racemic hit 18a showed good activity. Modification in decoration and chiral separation resulted in the 40 nM inhibitor,
- Tresadern, Gary,Delgado, Francisca,Delgado, Oscar,Gijsen, Harrie,MacDonald, Gregor J.,Moechars, Dieder,Rombouts, Frederik,Alexander, Richard,Spurlino, John,Gool, Michiel Van,Vega, Juan Antonio,Trabanco, Andres A.
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p. 7255 - 7260
(2012/02/04)
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- 3-AMINO-5-PHENYL-5,6-DIHYDRO-2H-[1,4]OXAZINE DERIVATIVES
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The present invention relates to 3-Amino-5-phenyl-5,6-dihydro-2H-[l,4]oxazine derivatives of formula (I) having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active
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Page/Page column 72
(2011/04/13)
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- 3-AMINO-5-PHENYL-5,6-DIHYDRO-2H-[1,4]OXAZINES
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The present invention relates to 3-Amino-5-phenyl-5,6-dihydro-2H-[1,4]oxazines of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. T
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