Adamed Pharma S.a.

Neurolixis

Universite Jagellone

Joanna Sniecikowska

Adam Bucki

Monika Marcinkowska

Marcin Kolaczkowski

Mark Andrew Varney

Adrian Newman-Tancredi

The invention relates to new 4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-indoles and 4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-benzimidazoles represented by formula (I), wherein all symbols and variables are as defined in the description. The compounds can find use in a method of prevention and/or treatment of diseases selected from the group consisting of Alzheimer's disease, Parkinson's disease, Levy body dementia, dementia-related psychosis, schizophrenia, delusional syndromes and other psychotic conditions related and not related to taking psychoactive substances, depression, anxiety disorders of various aetiology, sleep disorders of various aetiology.

Indole and benzimidazole derivatives as dual 5-HTand 5-HTreceptor antagonists

The invention relates to new 4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-indoles and 4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-benzimidazoles represented by formula (I), wherein all symbols and variables are as defined in the description. The compounds can find use in a method of prevention and/or treatment of diseases selected from the group consisting of Alzheimer's disease, Parkinson's disease, Lewy body dementia, dementia-related psychosis, schizophrenia, delusional syndromes and other psychotic conditions related and not related to taking psychoactive substances, depression, anxiety disorders of various aetiology, sleep disorders of various aetiology.

Indole and benzimidazole derivatives as dual 5-HT2A and 5-HT6 receptor antagonists

The invention relates to new 4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-indoles and 4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-benzimidazoles represented by formula (I), wherein all symbols and variables are as defined in the description. The compounds can find use in a method of prevention and/or treatment of diseases selected from the group consisting of Alzheimer's disease, Parkinson's disease, Levy body dementia, dementia-related psychosis, schizophrenia, delusional syndromes and other psychotic conditions related and not related to taking psychoactive substances, depression, anxiety disorders of various aetiology, sleep disorders of various aetiology. 

The invention concerns compounds that possess a high affinity at 5-HTreceptors and an agonist efficacy, as measured by Emax values from a cellular activation assay, that is higher than that of the compounds described in prior art. The capacity of the compounds of the invention to activate an effector protein complex is higher than that the most efficacious agonist described in prior art. Compounds of the invention also exhibit an exceptionally high selectivity (Ki ratio greater than 1000-fold) with respect, in particular, to dopamine D2 receptors and adrenergic receptors of the alpha1 subtype. This selectivity which constitutes a great advantage since it means that the compounds will avoid inducing (central and peripheral) effects associated with activating or inhibiting such receptors.

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Wieliczka, Poland

Joanna Sniecikowska