TAAR PYRAZOLE CARBOXAMIDE DERIVATIVES AS TAAR MODULATORS FOR USE IN THE TREATMENT OF SEVERAL DISORDERS SUCH AS DEPRESSION DIABETES AND PARKINSON'S DISEASE

摘要

The present invention relates to compounds of formula (I): EMI ID = In this formula, R ¹ is Phenyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, lower alkyl, lower cycloalkyl, lower alkoxy, cyano, halogen-substituted lower alkyl, hydroxy-substituted lower alkyl, Lower alkoxy), Pyridin-2, 3 or 4-yl which is optionally substituted with one or more substituents selected from the group consisting of halogen, lower alkyl, lower cycloalkyl, cyano, halogen-substituted lower alkyl, hydroxy-substituted lower alkyl, lower alkoxy, Alkoxy, or hydroxy-substituted lower alkoxy), Pyrimidine-2, 4 or 5-yl, which is optionally substituted by halogen, lower alkyl, lower cycloalkyl, hydroxy-substituted lower alkyl, or halogen- Pyrazin-2-yl, which is optionally substituted with halogen, lower alkyl, lower cycloalkyl, halogen-substituted lower alkyl, hydroxy-substituted lower alkyl or cyano, 2,2-difluorobenzo [d] [1,3] dioxol-5-yl, or Thiazolyl, which is optionally substituted with halogen-substituted lower alkyl; R ² is hydrogen or lower alkyl; R ³ is hydrogen, amino or lower alkyl; Z is a bond, -CH ₂ - or an -O-. It has now been found that the compounds of formula I have excellent affinities for the microamine related receptors (TAAR), in particular TAARl. The compounds may be used in the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological disorders such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, , Migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, energy consumption and assimilation disorders, body temperature homeostatic and dysfunction, circadian rhythm sleep disorders, and cardiovascular disorders Can be used for treatment.