SUBSTITUTED 2-IMIDAZOLES AS MODULATORS OF THE TRACE AMINE ASSOCIATED RECEPTORS

摘要

The present invention relates to a compound of formula (I) wherein R<SUP>1</SUP> is hydrogen or lower alkyl; R<SUP>2</SUP> is hydrogen or lower alkyl; R<SUP>3</SUP> is hydrogen, lower alkyl, lower alkoxy, phenyloxy, benzyloxy, halogen or lower alkyl substituted by halogen; R is hydrogen or lower alkyl and in case when n is 2, R may be the same or not; X is -CH<SUB>2</SUB>-, -CH- or -O-; Y is -CH<SUB>2</SUB>-, -CH- or a bond; when X is -O-, Y may not be a bond; Z is -CH<SUB>2</SUB>- or -CH-; m is 0, 1 or 2; when m is 2, R<SUP>2</SUP> may be the same or not; n is 0, 1 or 2; when n is 2, R<SUP>3</SUP> may be the same or not; and to pharmaceutically acceptable acid addition salts. It has been found that the compounds of formula (I) have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.