Janssen Pharmaceutica Nv

Vanderbilt University

Manuel Jesús Alcázar-Vaca

José Ignacio Andrés-Gil

José Manuel Bartolomé-Nebreda

Francisco Javier Fernández-Gadea

Craig William Lindsley

P Jeffrey Conn

Gregor James MacDonald

Shaun R Stauffer

Susana Conde-Ceide

Han Min Tong

Margaretha Henrica Maria Bakker

Frans E Janssens

Michiel Luc Maria Van Gool

Joseph Elisabeth Leenaerts

Marcel Frans Leopold De Bruyn

Maria Encarnacion Matesanz-Ballesteros

Ana Isabel De Lucas Olivares

Antonio Gómez-Sánchez

Frank Matthias Dautzenberg

Koenraad Arthur Van Rossem

Miguel Angel Pena-Piñón

Kristof Van Emelen

Joannes Theodorus Maria Linders

Carrie K Jones

Frank Tegtmeier

Antonius Adrianus Hendrikus Petrus Megens

Juan Antonio Vega Ramiro

Sergio-Alvar Alonso-de Diego

Guy Maurits R Bormans

Jacqueline Anne Macritchie

Francisca Delgado-Jiménez

Joaquin Pastor-Fernández

Pedro Martínez-Jiménez

Joost Verbeek

Sofie Jeanne Leopoldine Celen

Julen Oyarzabal Santamarina

Sonia Martinez Gonzalez

Jozef Leo Henri Van Reempts

José Manuel Bartolomé -Nebreda

Antonius Adrianus Hendrikus Megens

Jos Van Reempts

Kristol Van Emelen

Maria Encamacion Matesanz-Ballesteros

Chrysa Malosh

Rosa María Álvarez-Escobar

Donald Simpson

Juan Antonio Vega-Ramiro

Wilhelmus Helena Ignatius Maria Drinkenburg

José Ignacio ANDRÉS-Gil

Maria Lourdes Linares De La Morena

The present invention relates to novel, selective, radiolabelled mGluR2 ligands which are useful for imaging and quantifying the metabotropic glutamate receptor mGluR2 in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a mammal, in vitro or in vivo and to precursors of said compounds.

Radiolabelled mGluR2 PET ligands

The present invention relates to novel 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 2 ('mGluR2'). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention or treatment of disorders in which the mGluR2 subtype of metabotropic receptors is involved.

6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one compounds and their use as negative allosteric modulators of MGLUR2 receptors

In one aspect, the invention relates to substituted bicyclic alkoxy pyrazole analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Substituted bicyclic alkoxy pyrazole analogs as allosteric modulators of mGluR5 receptors

In one aspect, the invention relates to bicyclic triazole and pyrazole lactams, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Bicyclic triazole and pyrazole lactams as allosteric modulators of mGluR5 receptors

The present invention concerns aryl and heteroaryl substituted pyrazinone derivatives having antagonistic melanin-concentrating hormone (MCH) activity, in particular MCH-1 activity according to the general Formula (I) a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, an N-oxide form thereof or a quaternary ammonium salt thereof, wherein the variables are defined in Claim. It further relates to their preparation, compositions comprising them and their use as a medicine. The compounds according to the invention are useful for the prevention and/or treatment of psychiatric disorders, including but not limited to anxiety, eating disorders, mood disorders, such as bipolar disorders and depression, psychoses, such as schizophrenia, and sleeping disorders; obesity; diabetes; sexual disorders and neurological disorders.

Substituted pyrazinone derivatives for use in MCH-1 mediated diseases

The present invention concerns aryl and heteroaryl substituted diaza-spiro-pyridinone derivatives having antagonistic melanin-concentrating hormone (MCH) activity, in particular MCH-1 activity according to the general Formula (I) a pharmaceutically acceptable acid or base addition salt thereof, an N-oxide form thereof or a quaternary ammonium salt thereof, wherein the variables are defined in Claim. It further relates to their preparation, compositions comprising them and their use as a medicine. The compounds according to the invention are useful for the prevention and/or treatment of psychiatric disorders, including but not limited to anxiety, eating disorders, mood disorders, such as bipolar disorders and depression, psychoses, such as schizophrenia, and sleeping disorders; obesity; diabetes; sexual disorders and neurological disorders.

Substituted diaza-spiro-pyridinone derivatives for use in MCH-1 mediated diseases

The invention concerns a novel histamine receptor antagonist and the use of an histamine receptor antagonist for the reduction of intracranial pressure (ICP), in particular for the prevention and treatment of elevated intracranial pressure and/or secondary ischaemida, in particular caused by brain injury, more in particular caused by traumatic (TBI) and non-traumatic brain injury. The novel compounds comprise compounds according to the general Formula (I) the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof and the N-oxide form thereof. In particular, the preferred compound is 3-[2-[4-(11,12-dihydro-6H-benzimidazo[2,1-b][3]benzazepin-6-yl)-2-(phenyl-methyl)-1-piperidinyl]ethyl]-2,10-dimethyl pyrimido[1,2-&#x3b1;]benzimidazol-4(10H)-one, the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof and the N-oxide form thereof. Also claimed is the novel use of commercially available histamine H1-and H2-receptor antagonists for the reduction of intracranial pressure (ICP). 

Use of anti-histaminics for acute reduction of elevated intracranial pressure

 The invention concerns fused heterocyclic isoxazoline derivatives of Formula (I), the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof and the N-oxide form thereof, more in particular, tetrahydropyranoisoxazole, hexahydroisoxazolopyridine, tetrahydrothiopyrano isoxazole and hexahydrobenzoisoxazole derivatives fused to a heterocyclic ring system via the 6-membered ring of the bicyclic moiety as well as processes for their preparation, pharmaceutical compositions comprising them and their use as a medicine, in particular for treating depression, anxiety, movement disorders, psychosis, Parkinson's disease and body weight disorders including anorexia nervosa and bulimia, wherein the variables are defined as in ClaimThe compounds have surprisingly been shown to have selective serotonine (5-HT) reuptake inhibitor activity as well as &#x3b1;-adrenoceptor antagonist activity, compounds according to the invention are also suitable for treatment and/or prophylaxis in diseases where either one of the activities alone or the combination of said activities may be of therapeutic use.

Fused heterocyclic isoxazoline derivatives and their use as anti-depressants

The invention concerns novel substituted tetracyclic imidazole derivatives useful for the treatment of elevated intracranial pressure (ICP) and/or secondary ischaemia, in particular caused by brain injury, more in particular caused by traumatic (TBI) and non-traumatic brain injury, processes for their preparation, pharmaceutical compositions comprising them and their use as a medicine. The novel compounds comprise compounds according to the general Formula (I), the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof and the N-oxide form thereof. In particular, the preferred compound is 3-[2-[4-(11,12-dihydro-6H-benzimidazo[2,1-b][3]benzazepin-6-yl)-2-(phenyl-l-methyl)-1-piperidinyl]ethyl]-2,10-dimethyl pyrimido[1,2-&#x3b1;]benzimidazol-4(10H)-one, the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof and the N-oxide form thereof. 

Substituted tetracyclic imidazole derivatives, processes for their preparation, pharmaceutical compositions comprising them and their use as a medicine

The invention concerns substituted tricyclic isoxazoline derivatives, more in particular tricyclic dihydrobenzopyranoisoxazoline, dihydroquinolinoisoxazoline, dihydronaphthalenoisoxazoline and dihydrobenzothiopyranoisoxazoline derivatives substituted on at least one of the C6- and C9-positions of the phenylpart of the tricyclic moiety with a selected radical, according to Formula (I) wherein X=CH, N&#x2014;R, S or O, R, R, Rand Rare certain specific substituents, with the proviso that at least one of Rand Ris not hydrogen, Pir is preferably an optionally substituted piperidinyl or piperazinyl radical and Rrepresents an optionally substituted aromatic homocyclic or heterocyclic ring system including a partially or completely hydrogenated hydrocarbon chain of maximum 6 atoms long with which the ring system is attached to the Pir radical and which may contain one or more heteroatoms selected from the group of O, N and S; a process for their preparation, pharmaceutical compositions comprising them and their use as a medicine, in particular for the treatment of depression, anxiety, movement disorders, psychosis, Parkinson's disease and body weight disorders. The compounds according to the invention have surprisingly been shown to have a serotonine (5-HT) reuptake inhibitor activity in combination with additional &#x3b1;-adrenoceptor antagonist activity and show a strong anti-depressant activity without being sedative. The invention also relates to novel combination of isoxazoline derivatives according to the invention with one or more other compounds selected from the group of antidepressants, anxiolytics, anti-psychotics and anti-Parkinson's disease drugs to improve efficacy and/or onset of action.

C6-and C9-substituted chromeno[4,3-c]isoxazoline derivatives and their use as anti-depressants

The present invention concerns compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, wherein -a&#x2550;a-a&#x2550;a- is a bivalent radical wherein one or two of ato aare nitrogen and the remaining ato aare &#x2014;CH&#x2550;; -Z-Z- is a bivalent radical; -A- is a bivalent radical of formula &#x2014;N(R)-Alk- or a 5, 6 or 7-membered saturated heterocycle containing one or two nitrogen atoms; R, Rand Rare each independently selected from hydrogen, Calkyl, hydroxy, halo and the like; Alkand Alkare optionally substituted Calkanediyl; Ris a radical of formula wherein n is 1 or 2; pis 0, and pis 1 or 2; or pis 1 or 2, and pis 0; X is oxygen, sulfur or &#x2550;NR; Yis oxygen or sulfur; Ris hydrogen, Calkyl, Ccycloalkyl, phenyl or phenylmethyl; Ris Calkyl, Ccycloalkyl phenyl or phenylmethyl; Ris cyano, Calkyl, Ccycloalkyl, Calkyloxycarbonyl or aminocarbonyl; Ris hydrogen or Calkyl; and Q is a bivalent radical. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to disturbed fundic accomodation.

Compounds for treating fundic disaccomodation

The invention concerns substituted amino isoxazoline derivatives, more in particular tricyclic dihydrobenzopyranoisoxazoline, dihydroquinolinoisozazoline, dihydronaphthalenoisoxazoline and dihydrobenzothiopyranoisoxazoline derivatives substituted on the phenylpart of the tricyclic moiety with primary, secondary and/or tertiary amino groups, according to Formula (I) wherein X=CH, N&#x2014;R, S or O, R, Rand Rare certain specific substituents, with the proviso that at least one of Rand Ris an amino radical of formula N&#x2014;RRwherein Rand Rare each a variety of radicals, Pir is an optionally substituted piperidyl or piperazyl radical and Rrepresents an optionally substituted aromatic homocyclic or heterocyclic ring system including a partially or completely hydrogenated hydrocarbon chain of maximum 6 atoms long with which the ring system is attached to the Pir radical and which may contain one or more heteroatoms selected from the group of O, N and S; a process for their preparation, pharmaceutical compositions comprising them and their use as a medicine, in particular for the treatment of depression and/of anxiety and disorders of body weight. The compounds according to the invention have surprisingly been shown to have a serotonin (5-HT) reuptake inhibitor activity in combination with additional &#x3b1;-adrenoceptor antagonist activity and show a strong anti-depressant activity without being sedative. Compounds according to the invention are also suitable for treating depression, anxiety and body weight disorders. The invention also relates to novel combination of substituted amino isoxazoline derivatives according to the invention with antidepressants, anxiolytics and/or antipsychotics to improve efficacy and/or onset of action.

Substituted amino isoxazoline derivatives and their use as anti-depressants

The present invention concerns compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharma-ceutically acceptable acid addition salt thereof, wherein &#x2014;a&#x2550;a&#x2014;a&#x2550;a&#x2014; is a bivalent radical wherein one or two of ato aare nitrogen and the remaining ato aare &#x2014;CH&#x2550;; &#x2014;Z&#x2014;Z&#x2014; is a bivalent radical; &#x2014;A&#x2014; is a bivalent radical of formula &#x2014;N(R)&#x2014;Alk&#x2014; or a 5, 6 or 7-membered saturated heterocycle containing one or two nitrogen atoms; R, Rand Rare each independently selected from hydrogen, Calkyl, hydroxy, halo and the like; Alkand Alkare optionally substituted Calkanediyl; Ris a radical of formula (d-1), (d-2), (d-3), (d-4), (d-5) wherein n is 1 or 2; pis 0, and pis 1 or 2; or pis 1 or 2, and pis 0; X is oxygen, sulfur or &#x2550;NR; Yis oxygen or sulfur; Ris hydrogen, Calkyl, Ccycloalkyl, phenyl or phenylmethyl; Ris Calkyl, Ccycloalkyl phenyl or phenylmethyl; Ris cyano, Calkyl, Ccyclo-alkyl, Calkyloxycarbonyl or aminocarbonyl; Ris hydrogen or Calkyl; and Q is a bivalent radical. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to disturbed fundic accomodation 

Compounds for treating impaired fundic relaxation

Growing community of inventors

Toledo, Spain

Manuel Jesús Alcázar-Vaca