Boehringer Ingelheim International Gmbh

Holger Rosenbrock

Riccardo Giovannini

Niklas Heine

Gerhard Schaenzle

Christian Eickmeier

Klaus Fuchs

Dennis Fiegen

Thomas Fox

Cornelia Dorner-Ciossek

Sanjaya Singh

Martin Hendrix

Marco Ferrara

Remko Alexander Bakker

Michael Dziegelewski

Vladimir H Voynov

Sarah Low

Haiguang Xiao

Sathyadevi Venkataramani

Sebastian Bandholtz

Peter Michael Benz

Rolf Herrmann

Cynthia Hess Kenny

Heiko Friedrich Stahl

Christoph Hoenke

Iain Lingard

Ulrike Werthmann

Rocco Mazzaferro

Uta Friederike Lessel

Bernhard Schmid

Bodo Betzemeier

Barbara Bertani

Lore Florin

Masanori Ito

Manabu Nakatani

Yohei Kawabata

Masashi Adachi

Yihua Zhao

Michael Steven Sand

Marco Ferrera

Cornelia Dornier-Ciossek

Tobias Brodmann

Takayuki Kamata

Daniel Marckart

Lore Katharina Florin

Jana Podhorna

Sun Young Yum

The invention relates to the treatment of cognitive impairment associated with schizophrenia (CIAS) with a specific GlyT1 inhibitor ([5-(methylsulfonyl)-2-{[(2R)-1,1,1-trifluoropropan-2-yl]oxy}phenyl]{(1R,5R)-1-[5-(trifluoromethyl)-1,2-oxazol-3-yl]-3-azabicyclo[3.1.0]hex-3-yl}methanone). A 12-week treatment in a phase 2 study showed improvement in cognitive function as measured by the MATRICS Consensus Cognitive Battery (MCCB) overall composite score.

Treatment of cognitive impairment associated with schizophrenia

The present invention relates to novel agonistic anti-TrkB antibodies and therapeutic and diagnostic methods and compositions for using the same.

Anti-TrkB antibodies

The present invention relates to compound III and its use for treatment and/or prevention of diseases of the schizophrenia spectrum and other psychotic disorders, first episodes of these diseases such as first episode of psychosis (FEP), relapses of these diseases such as reduction of relapse in patients with schizophrenia (REX). The invention also relates to polymorphs of compound III, and pharmaceutical compositions comprising compound III and/or its polymorphs.

Medical use of compound III

The invention relates to novel 6-Cycloalkyl-pyrazolopyrimidinones according to formula (I). wherein Ris a 5 or 6 membered aromatic heteroaryl-group, Ris an optional substituent, D is optionally substituted cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl or 2-, 3- or 4-pyridyl, m=1 or 2 and n is 0, 1 or 2. The new compounds are for use as the active entity of medicaments or for the manufacture of medicaments respectively, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. Such conditions may for example be associated with Alzheimer's disease, schizophrenia and other diseases. The new compounds are also for example for the manufacture of medicaments and/or for use in the treatment of these diseases, in particular for cognitive impairment associated with such disease. The compounds of the invention show PDE9 inhibiting properties.

6-cycloalkyl-pyrazolopyrimidinones for the treatment of CNS disorders

The present inventions relate to substituted piperazine derivatives of general formula (I) and to the manufacture of said compounds, pharmaceutical compositions comprising a compound according to general formula (I), and the use of said compounds for the treatment of various medical conditions related to glycine transporter-1 (GlyT1).

Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1

The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones of formula (I), in which Hc is a tetrahydropyranyl-group and Ris the group V&#x2014;W&#x2014;*, whereby V and W independently of each other may be an aryl group or an heteroaryl group, which independently of each other may optionally be substituted. According to one aspect of the invention the new compounds are for use as medicaments or for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. The new compounds are also for the manufacture of medicaments and/or for use in the treatment of e.g. Alzheimer's disease, in particular for cognitive impairment associated with Alzheimer's disease.

Compounds for the treatment of CNS disorders

The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones, wherein i.) the nitrogen atom of the pyrazolo-group that is next to the pyrimidino-group is attached to a non-aromatic, organic heterocycle having at least one ring hetero atom selected from O, N and S and ii.) to the C-atom between the two nitrogen atoms of the pyrimidinone-ring a second substituent is bound via an optionally substituted methylene-bridge. According to one aspect of the invention the new compounds are for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. The new compounds are also for the manufacture of medicaments for the treatment of Alzheimer's disease.

1-heterocyclyl-1,5-dihydro-pyrazolo[3,4-D] pyrimidin-4-one derivatives and their use as PDE9A modulators

The invention relates to novel cycloalkyl- or cycloalkenyl-substituted pyrazolopyrimidinones of formula (I). wherein A, R-Rand x are as defined herein, and their use as medicaments for improving perception, concentration, learning and/or memory in patients in need thereof.

Substituted phenyl-3-aza-bicyclo[3.1.0]hex-3-yl-methanones which are glycine transporter-1 (GlyT1) inhibitors. These are useful for the treatment of schizophrenia, Alzheimer's Disease and other neurological and psychiatric disorders.

Phenyl-3-aza-bicyclo[3.1.0]hex-3-yl-methanones and the use thereof as medicament

The invention relates to novel 6-cycloalkyl-pyrazolopyrimidinones according to formula (I) wherein R, R, D, m and n are as defined herein. The invention also relates to medicaments comprising these compounds and methods of using these compounds in the treatment of diseases and conditions, particularly diseases or conditions concerning deficits in perception, concentration, learning or memory.

The invention relates to novel substituted pyrazolopyrimidines. Chemically, the compounds are characterized by general Formula (I): with Rbeing phenyl or pyridyl, any of which is substituted with 1 to 4, preferably 1 to 3 substituents X; X independently of each other being selected from C-C-alkyor Ci-C-alkoxy, where C-C-alkyl and C-C-alkoxy are at least dihalogenated up to perhalogenated. preferably with 2 to 6 halogen substituents, and the halogen atoms being selected from the group of fluoro, chloro and bromo, preferably fluoro; Rbeing phenyl or heteroaryl, where phenyl is substituted by 1 to 3 radicals and heteroaryl is optionally substituted by 1 to 3 radicals in each case independently of one another selected from the group of C-C-alkyl, C-C-alkoxy, hydroxycarbonyl, cyano, trifluoromethyl, amino, nitro, hydroxy, C-C-alkylamino, halogen, C-C-arylcarbonylamino, C-C-alkylcarbonylamino, C-C-alkylaminocarbonyl. C-C-alkoxycarbonyl, C-C-arylaminocarbonyl, heteroarylaminocarbonyl. heteroarylcarbonylamino, C-C-alkylsulphonyl-amino, C-C-alkylsulphonyl and C-C-alkylthio; The new compounds shall be used for the manufacture of medicaments, in particular medicaments for improving, perception, concentration, learning and/or memory in patients in need thereof. 

1, 5-dihydro-pyrazolo (3, 4-D) pyrimidin-4-one derivatives and their use as PDE9A mudulators for the treatment of CNS disorders

The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones, Formula (I) with is a mono-, bi- or tri-cyclic heterocyclyl group, the ring members of which are carbon atoms and at least 1, preferably 1, 2 or 3, heteroatom(s), which are selected from the group of nitrogen, oxygen and sulphur, which is in the form of &#x2014;S(O)&#x2014; with r being 0, 1 or 2, and&#x2014;said heterocyclyl group is or comprises 1 non-aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member and&#x2014;said heterocyclyl group is bound to the scaffold by said 1 non-aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member. According to one aspect of the invention the new compounds are for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. The new compounds are also for the manufacture of medicaments for the treatment of Alzheimer's disease. 

1-heterocyclyl-1,5-dihydro-pyrazolo[3,4-D] pyrimidin-4-one derivates and their use as PDE9A modulators

The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones of formula (I), in which Hc is a tetrahydropyranyl-group and Ris the group V&#x2212;W&#x2212;*, whereby V and W independently of each other may be an aryl group or an heteroaryl group, which independently of each other may optionally be substituted. According to one aspect of the invention the new compounds are for use as medicaments or for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. The new compounds are also for the manufacture of medicaments and/or for use in the treatment of e.g. Alzheimer's disease, in particular for cognitive impairment associated with Alzheimer's disease.

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Mittelbiberach, Germany

Holger Rosenbrock