| abstract |
The invention relates to compounds of formula I wherein R is hydrogen or lower alkyl; R 1 is -(CH 2 ) n -(O) o -heterocycloalkyl or -C(O)-heterocycloalkyl, wherein the heterocycloalkyl group is optionally substituted by lower alkyl, hydroxy, halogen or by -(CH 2 ) p -aryl; n is 0, 1 or 2; o is 0 or 1; p is 0, 1 or 2; R 2 is CF 3 , cycloalkyl, optionally substituted by lower alkoxy or halogen, or is indan-2-yl, or is heterocycloalkyl, optionally substituted by heteroaryl, or is aryl or heteroaryl, wherein the aromatic rings are optionally substituted by one or two substituents, selected from lower alkyl, halogen, heteroaryl, hydroxy, CF 3 , OCF 3 , OCH 2 CF 3 , OCH 2 -cycloalkyl, OCH 2 C(CH 2 OH)(CH 2 C1)(CH 3 ), S-lower alkyl, lower alkoxy, CH 2 -lower alkoxy, lower alkinyl or cyano, or by-C(O)-phenyl, -O-phenyl, -O- CH 2 -phenyl, phenyl or -CH 2 -phenyl, and wherein the phenyl rings may optionally be substituted by halogen, -C(O)-lower alkyl, -C(O)OH or -C(O)O-lower alkyl, or the aromatic rings are optionally substituted by heterocycloalkyl, OCH 2 -oxetan-3-yl or O-tetrahydropyran-4-yl, optionally substituted by lower alkyl; X is a bond, -NR'-, -CH 2 NH-, -CHR''-, -(CHR'') q -O-, -O-(CHR'') q - or -(CH 2 ) 2 -; Y is a bond or -CH 2 - R' is hydrogen or lower alkyl, R'' is hydrogen, lower alkyl, CF 3 , lower alkoxy, q is 0, 1, 2 or 3; or to a pharmaceutically suitable acid addition salt thereof. It has now 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 Parkinsons disease, neurodegenerative disorders such as Alzheimers 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. |