Isoquinoline derivatives

Inventors: Simona M. Ceccarelli, Ravi Jagasia, Roland Jakob-Roetne, Rainer E. Martin, Juergen Wichmann

• Assignee: Hoffmann La Roche Inc

The present invention relates to the use of compounds of general formula

wherein
R¹ is phenyl or pyridinyl, which are optionally substituted by halogen, cyano or lower alkyl substituted by halogen, or is dihydro-pyran-4-yl;
R² is hydrogen or lower alkyl;
R³ is —(CHR)n-phenyl, optionally substituted by lower alkoxy or S(O)2-lower alkyl,or is heterocycloalkyl, optionally substituted by ═O and lower alkyl,
or is —(CH2)n-five or six membered heteroaryl, optionally substituted by lower alkyl,
or is hydrogen, lower alkyl, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, —NR—S(O)2-lower alkyl, —(CH2)n-cycloalkyl or —(CH2)n—S(O)2-lower alkyl; or
R² and R³ form together with the N-atom to which they are attached a heterocycloalkyl ring, selected from the group consisting of 1,1-dioxo-thiomorpholinyl, morpholinyl, or pyrrolidinyl, optionally substituted by hydroxyl;
R is hydrogen or lower alkyl;
n is 0, 1 or 2;
or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof,
for the treatment of schizophrenia, obsessive-compulsive personality disorder, depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson’s disease, dementia, Alzheimer’s disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction (“chemobrain”), Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington’s disease, stroke, and disturbances due to radiation therapy, chronic stress, optic neuropathy or macular degeneration, or abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine or cocaine.

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