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נגזרות פיראזול קארבוקסאמיד בתור מודולטורים של taar לשימוש בטיפול במחלות קשות כגון דכאון, סוכרת ומחלת פארקינסון
专利权人:
F. HOFFMANN-LA ROCHE AG
发明人:
申请号:
IL23733215
公开号:
IL237332A
申请日:
2015.02.19
申请国别(地区):
IL
年份:
2018
代理人:
摘要:
The present invention relates to compounds of formula wherein R1 is phenyl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkoxy, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, lower alkoxy substituted by halogen or lower alkoxy substituted by hydroxy; or is pyridine-2, 3 or 4-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, lower alkoxy, lower alkoxy substituted by halogen or lower alkoxy substituted by hydroxyl; or is pyrimidin-2, 4 or 5-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkyl substituted by hydroxy or lower alkyl substituted by halogen; or is pyrazin-2-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy or cyano; or is 2,2-difluorobenzo[d][1,3]dioxol-5-yl, or is thiazolyl, optionally substituted by lower alkyl substituted by halogen; R2 is hydrogen or lower alkyl; R3 is hydrogen, amino or lower alkyl; Z is a bond, —CH2— or —O—; or to a pharmaceutically suitable acid addition salt thereof. It has now been found that the compounds of formulas 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 ca
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