Janssen Pharmaceutica Nv

Pedro Martínez-Jiménez

Francisco Javier Fernández-Gadea

Frans E Janssens

Joseph Elisabeth Leenaerts

José Manuel Bartolomé-Nebreda

Manuel Jesús Alcázar-Vaca

Antonio Gómez-Sánchez

Koenraad Arthur Van Rossem

José Ignacio Andrés-Gil

Victor Karel Sipido

Frank Tegtmeier

Jozef Leo Henri Van Reempts

Jos Van Reempts

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 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

Isoxazolidine derivatives

Growing community of inventors

Madrid, Spain

Pedro Martínez-Jiménez