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    • 1. 发明公开
    • 미량 아민 결합 수용체(TAAR)에 대한 양호한 친화도를 갖는 2-이미다졸린
    • 对咪唑类相关受体(TAARS)有良好的亲和力的2-IMIDAZOLINES
    • KR1020100028661A
    • 2010-03-12
    • KR1020107002350
    • 2008-06-24
    • 에프. 호프만-라 로슈 아게
    • 갈레이구이도그로에브케쯔빈덴카트린노르크로스로저스탈더헨리
    • C07D233/52C07D405/12A61K31/415A61P25/00
    • C07D233/24C07D233/20C07D233/22C07D233/42C07D233/52C07D405/12
    • The present invention relates to compounds of formula (I) wherein X-Y is-N(R)-CH(R)-, CH(R)-N(R)-,-NH-NH-,-O-CHR-,-CHR-O-,-S-CHR,-CHR-S-or-CHR-CHR-; Ris hydrogen, halogen, lower alkyl, lower alkoxy,-(CH)-phenyl optionally substituted by lower alkoxy,-(CH)-C(O)-phenyl optionally substituted by lower alkoxy,-(CH)-O-phenyl optionally substituted by lower alkoxy,-(CH)-O-phenyl, CF, cycloalkyl, NO, amino or hydroxy; Ris hydrogen, lower alkyl, phenyl optionally substituted by hydroxy or benzyl; R/Rare independently from each other hydrogen, lower alkyl or benzyl; Ar is phenyl, naphthyl, benzofuranyl or benzo [1,3] dioxolyl; n is 1, 2, 3 or 4; o is 0, 1, 2, 3 and to their pharmaceutically active 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.
    • 本发明涉及式(I)化合物,其中XY是-N(R)-CH(R) - ,CH(R)-N(R) - , - NH-NH - , - O-CHR - CHR-O - , - S-CHR,-CHR-S-或-CHR-CHR-; 任选被低级烷氧基取代的 - (CH)-C(O) - 苯基,任选被低级烷氧基取代的 - (CH)-O-苯基, - (CH) - (CH)-O-苯基,CF,环烷基,NO,氨基或羟基; R 1是氢,低级烷基,任选被羟基或苄基取代的苯基; R / Rare彼此独立地为氢,低级烷基或苄基; Ar是苯基,萘基,苯并呋喃基或苯并[1,3]二氧杂环戊烯基; n为1,2,3或4; o是0,1,2,3及其药学活性盐。已经发现式(I)化合物对微量胺相关受体(TAAR)具有良好的亲和力,特别是对于TAAR1。 这些化合物可用于治疗抑郁症,焦虑障碍,双相情感障碍,注意力缺陷多动障碍(ADHD),应激相关疾病,精神病性精神障碍如精神分裂症,神经系统疾病如帕金森病,神经变性疾病如阿尔茨海默病, 癫痫,偏头痛,高血压,药物滥用和代谢障碍如进食障碍,糖尿病,糖尿病并发症,肥胖症,血脂异常,能量消耗和同化障碍,体温平衡紊乱和失调,睡眠和昼夜节律紊乱以及心血管疾病 。