公开(公告)号：JP2013173779A

公开(公告)日：2013-09-05

申请号：JP2013096834

申请日：2013-05-02

Applicant: F Hoffmann La Roche Ag ,  エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft

Inventor： GALLEY GUIDO ,  GOERGLER ANNICK ,  GROEBKE ZBINDEN KATRIN ,  NORCROSS ROGER ,  STALDER HENRI

IPC: C07D233/64 ,  A61K31/417 ,  A61K31/4178 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4709 ,  A61K31/497 ,  A61K31/506 ,  A61K31/517 ,  A61K31/5377 ,  A61P3/00 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P9/00 ,  A61P9/12 ,  A61P25/06 ,  A61P25/08 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12

CPC classification number: C07D233/64

Abstract: PROBLEM TO BE SOLVED: To provide a compound which has a good affinity to the trace amine associated receptor (TAAR) and which can be used for the treatment of depression, an anxiety disorder, a bipolar disorder, an attention deficit hyperactivity disorder (ADHD), a stress-related disorder, a psychotic disorder, and a cardiovascular disorder or the like.SOLUTION: A compound is selected from a group of aminomethyl-4-imidazole compounds exemplified by formula.

Abstract translation: 要解决的问题：提供对微量胺相关受体（TAAR）具有良好亲和力的化合物，其可用于治疗抑郁症，焦虑症，双相情感障碍，注意缺陷多动障碍（ADHD） ，应激相关疾病，精神病性障碍和心血管疾病等。溶液：化合物选自由式表示的氨基甲基-4-咪唑化合物。

公开(公告)号：JP2010229153A

公开(公告)日：2010-10-14

申请号：JP2010138970

申请日：2010-06-18

Applicant: F Hoffmann La Roche Ag ,  エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft

Inventor： FLOHR ALEXANDER ,  GALLEY GUIDO ,  JAKOB-ROETNE ROLAND ,  KITAS ERIC ARGIRIOS ,  PETERS JENS-UWE ,  WOSTL WOLFGANG

IPC: C07D223/18 ,  A61K31/335 ,  A61K31/55 ,  A61K31/5513 ,  A61P25/28 ,  A61P43/00 ,  C07D223/16 ,  C07D223/20 ,  C07D243/24 ,  C07D273/00 ,  C07D313/14

CPC classification number: C07D223/16 ,  A61K31/335 ,  A61K31/55 ,  A61K31/5513 ,  C07D223/20 ,  C07D243/24 ,  C07D273/00 ,  C07D313/14

Abstract: PROBLEM TO BE SOLVED: To provide compounds blocking activity of γ-secretase able to be used for treating Alzheimer's disease. SOLUTION: Malonamide derivatives expressed by formula (I) [in formula (I), R 1 represents a group expressed by formula (a)], pharmaceutically suitable acid addition salts, optically pure enantiomers, racemates or diastereomeric mixtures thereof are provided. COPYRIGHT: (C)2011,JPO&INPIT

Abstract translation: 待解决的问题：提供能够用于治疗阿尔茨海默氏病的γ-分泌酶的化合物阻断活性。 式（I）[式（I）中R 1表示的丙二酰胺衍生物表示由式（a）表示的基团]，药学上合适的酸加成盐，光学纯对映异构体， 提供了外消旋物或非对映体混合物。 版权所有（C）2011，JPO＆INPIT

公开(公告)号：JP2000247957A

公开(公告)日：2000-09-12

申请号：JP2000047003

申请日：2000-02-24

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL ,  BRANCA QUIRICO ,  GALLEY GUIDO ,  GODEL THIERRY ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK ,  STADLER HEINZ

IPC: A61K20060101 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/444 ,  A61K31/455 ,  A61K31/496 ,  A61P1/00 ,  A61P9/00 ,  A61P11/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/28 ,  A61P25/30 ,  A61P27/02 ,  A61P29/00 ,  A61P43/00 ,  C07D20060101 ,  C07D213/30 ,  C07D213/38 ,  C07D213/40 ,  C07D213/63 ,  C07D213/65 ,  C07D213/74 ,  C07D213/75 ,  C07D213/78 ,  C07D213/82 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D413/14

Abstract: PROBLEM TO BE SOLVED: To obtain a new 4-phenylpyridine derivative which is a neurokinin 1 receptor antagonist and is useful for pain, headache, Alzheimer's disease, multiple sclerosis, amorphinism relaxation, cardiovascular change, swelling, chronic inflammatory diseases, respiratory diseases, and the like. SOLUTION: A compound of formula I [R is H, a lower alkyl, a lower alkoxy, a halogen or the like; R1 is H or a halogen; R2, R2' are each H, a halogen, trifluoromethyl, a lower alkoxy or cyano, or R and R1, R2 and R2' together form CH=CH-CH=CH which may be substituted by one or more alkyls or the like; R3 is H, a lower alkyl or a cycloalkyl; R4 is H, N(R5)2 (R5 is H, a 3-6C cycloalkyl or the like) or the like; R6 is H, OH, a lower alkyl or the like; X is C(O)N(R5) or the like; (n) is 0-4; (m) is 1 or 2]. For example, N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-4-o-tolyl-nicotinamide. The compound of formula I is obtained, for example, by reacting a compound of formula II with a compound of formula III.

公开(公告)号：JPH11228575A

公开(公告)日：1999-08-24

申请号：JP34527898

申请日：1998-12-04

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  CESURA ANDREA ,  GALLEY GUIDO ,  JENCK FRANCOIS ,  ROEVER STEPHAN ,  WICHMANN JUERGEN

IPC: C07D235/02 ,  A61K31/00 ,  A61K31/41 ,  A61K31/435 ,  A61K31/438 ,  A61P3/00 ,  A61P3/04 ,  A61P9/00 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/08 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07D207/04 ,  C07D233/30 ,  C07D471/10

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful for treating diseases associated with an Orphanin FQ(OFQ) receptor such as anxiety disorder and stress disorder, depression, trauma and amnesia due to Alzheimer disease or other dementias. SOLUTION: This compound is represented by formula I (R is H or the like; R is H or the like; R is H or the like; R is H or the like; A is a ring system or the like such as a 5-15C cycloalkyl which may be substituted with a lower alkyl or the like in addition to R ), preferably 8-(decahydro-naphthalen-2- yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one or the like. The compound represented by formula I is obtained by reductively aminating a compound represented by formula II [e.g. octahydro-2-(1H)-naphthalenone] with a compound represented by formula III e.g. 1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one} in the presence of a reducing agent such as sodium borohydride in a solvent such as toluene.

公开(公告)号：JPH10212290A

公开(公告)日：1998-08-11

申请号：JP1371198

申请日：1998-01-27

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  CESURA ANDREA ,  GALLEY GUIDO ,  JENCK FRANCOIS ,  MONSMA FREDERICK ,  ROEVER STEPHAN ,  WICHMANN JUERGEN

IPC: C07D233/04 ,  A61K31/00 ,  A61K31/41 ,  A61K31/435 ,  A61K31/438 ,  A61K31/445 ,  A61K31/55 ,  A61K51/02 ,  A61P3/04 ,  A61P3/12 ,  A61P9/00 ,  A61P9/12 ,  A61P25/00 ,  A61P25/04 ,  A61P25/08 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07D215/58 ,  C07D305/14 ,  C07D471/00 ,  C07D471/10 ,  C07D498/00

Abstract: PROBLEM TO BE SOLVED: To obtain the subject new compound which is an agonist for OFQ receptor and/or an antagonist useful for treating mental disturbance, nervous disturbance and physiological disorder. SOLUTION: This compound is shown by formula I (R and R are each H, a lower alkyl, etc.; R is phenyl; R is H, a lower alkyl, an acyl, etc.; R and R are each H, a lower alkyl, etc., or bonded together to form a phenyl ring; R and one of R and R can be bonded to form a 6-memered ring; A is a saturated 4- to 7-membered ring containing a hetero atom such as O or S) or its acid addition salt such as 8-(8-chloro-1,2,3,4,-tetrahydro-naphthyl-2)-1- phenyl-1,3,8-triaza-spiro[4,5]decan-4-one. The compound of formula I is obtained by hydrogenating a double bond in a compound of formula II (A' is a 5 to 7-membered ring containing a hetero atom such as O or S). The compound is useful for treating anxiety, stress disorder, depression, traumatic disorder, amnesia caused by Alzheimer's disease or other dementia, epilepsy and convulsion.

公开(公告)号：WO2007085556A2

公开(公告)日：2007-08-02

申请号：PCT/EP2007050441

申请日：2007-01-17

Applicant: HOFFMANN LA ROCHE ,  GALLEY GUIDO ,  GROEBKE ZBINDEN KATRIN ,  HOENER MARIUS ,  NORCROSS ROGER ,  STALDER HENRI

Inventor： GALLEY GUIDO ,  GROEBKE ZBINDEN KATRIN ,  HOENER MARIUS ,  NORCROSS ROGER ,  STALDER HENRI

IPC: C07D405/06 ,  A61K31/4174 ,  A61K31/4178 ,  A61P25/00 ,  C07D233/54

CPC classification number: C07D233/64 ,  C07D405/06

Abstract: The present invention relates to the use of compounds of formula (I) wherein R is hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy, phenyl, S-phenyl or O-phenyl, which are optionally substituted by lower alkoxy or halogen, or is benzyloxy, C(O)O-lower alkyl, cycloalkyl, or is lower alkyl or lower alkoxy substituted by halogen; Ar is aryl or heteroaryl, selected from the group consisting of phenyl, naphthyl, pyridinyl, benzofuranyl, dihydrobenzofuranyl or pyrazole; R 1 /R 1' are independently from each other hydrogen, hydroxy, lower alkyl, lower alkoxy or are phenyl or benzyl, which are optionally substituted by halogen; R 2 is hydrogen or lower alkyl; n is 1, 2, 3 or 4; and to their pharmaceutically active salts, racemic mixtures, enantiomers, optical isomers and tautomeric forms for the preparation of medicaments for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, 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.

Abstract translation: 本发明涉及任选被低级烷氧基或卤素取代的式（I）化合物（其中R为氢，卤素，低级烷基，低级烷氧基，羟基，苯基，S-苯基或O-苯基）的用途，或 是苄氧基，C（O）O-低级烷基，环烷基或是被卤素取代的低级烷基或低级烷氧基; Ar是选自苯基，萘基，吡啶基，苯并呋喃基，二氢苯并呋喃基或吡唑的芳基或杂芳基; R 1，R 1，R 1相互独立地为氢，羟基，低级烷基，低级烷氧基或是苯基或苄基，它们任选地被卤素取代; R 2是氢或低级烷基; n是1,2,3或4; 及其药学活性盐，外消旋混合物，对映异构体，光学异构体和互变异构形式，用于制备治疗抑郁症，焦虑症，双相性精神障碍，注意力缺陷多动障碍，压力相关障碍，精神障碍如精神分裂症， 帕金森病等神经疾病，阿尔茨海默氏病等神经变性疾病，癫痫症，偏头痛，高血压，药物滥用，代谢障碍如进食障碍，糖尿病，糖尿病并发症，肥胖症，血脂障碍，能量消耗和同化障碍， 体温平衡，睡眠和昼夜节律紊乱以及心血管疾病。

公开(公告)号：WO2008074679A3

公开(公告)日：2008-10-09

申请号：PCT/EP2007063585

申请日：2007-12-10

Applicant: HOFFMANN LA ROCHE ,  GALLEY GUIDO ,  GROEBKE ZBINDEN KATRIN ,  NORCROSS ROGER ,  STALDER HENRI

Inventor： GALLEY GUIDO ,  GROEBKE ZBINDEN KATRIN ,  NORCROSS ROGER ,  STALDER HENRI

IPC: C07D233/64 ,  A61K31/415 ,  A61P9/00 ,  A61P25/00

CPC classification number: C07D233/64

Abstract: The invention relates to compounds of formula (I) wherein R is hydrogen, lower alkyl or amino; X-R 1 is -CH 2 -, -CH(lower alkoxy)- or -CH(OH)- and Y-R 2 is -CH 2 , -CH(lower alkyl)-, -CH(lower alkoxy)- -O-, -S-, -S(O)-, -S(O) 2 -, -CH(phenyl)- or -C(lower alkyl) 2 -; or X-R 1 is -NH- and Y-R 2 is -CH 2 , -CH(lower alkyl)-, -CH(lower alkoxy)-, -CH(phenyl)- or -C(lower alkyl) 2 -; Ar is phenyl, napthyl or benzofuranyl, which rings are unsubstituted or substituted by one or more substituents, selected from the group consisting of lower alkyl, lower alkyl substituted by halogen, halogen, lower alkoxy, lower alkoxy substituted by halogen, hydroxy, amino, di-alkylamino, morpholinyl, phenyl, benzyl or by O-benzyl; or to pharmaceutically suitable 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.

Abstract translation: 本发明涉及式（I）的化合物，其中R是氢，低级烷基或氨基; XR 1是-CH 2 - ， - CH（低级烷氧基） - 或-CH（OH） - 且YR 2是-CH 2 - （低级烷基） - ， - CH（低级烷氧基）-O - ， - S - ， - S（O） - ， - S（O）2

公开(公告)号：WO2008058867A3

公开(公告)日：2008-07-10

申请号：PCT/EP2007061921

申请日：2007-11-06

Applicant: HOFFMANN LA ROCHE ,  GALLEY GUIDO ,  GROEBKE ZBINDEN KATRIN ,  NORCROSS ROGER ,  STALDER HENRI

Inventor： GALLEY GUIDO ,  GROEBKE ZBINDEN KATRIN ,  NORCROSS ROGER ,  STALDER HENRI

IPC: C07D403/06 ,  A61K31/4178 ,  C07D401/06 ,  C07D413/06

CPC classification number: C07D401/06 ,  C07D403/06 ,  C07D413/06

Abstract: The present invention relates to compounds of formula (I) wherein R 1 is hydrogen or lower alkyl; R 2 is hydrogen or lower alkyl; R 3 is hydrogen, lower alkyl, lower alkoxy, phenyloxy, benzyloxy, halogen or lower alkyl substituted by halogen; R 4 is hydrogen or lower alkyl; X is -CH 2 -, -CH- or -O-; Y is -CH 2 -, -CH 2 CH 2 -, -CH- or a bond; when X is -O-, then Y is -CH 2 -; Z is -CH 2 - or -CH-; m is 1 or 2; when m is 2, R 2 may be the same or not; n is 1 or 2; when n is 2, R 3 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.

Abstract translation: 本发明涉及其中R 1为氢或低级烷基的式（I）化合物; R 2是氢或低级烷基; R 3是氢，低级烷基，低级烷氧基，苯氧基，苄氧基，卤素或被卤素取代的低级烷基; R 4是氢或低级烷基; X是-CH 2 - ， - CH-或-O-; Y是-CH 2 - ， - CH 2 CH 2 - ， - CH-或键; 当X是-O-时，则Y是-CH 2 - 。 Z是-CH 2 - 或-CH-; m为1或2; 当m为2时，R 2可以相同或不相同; n为1或2; 当n为2时，R 3可以相同或不相同; 和药学上可接受的酸加成盐。 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。 该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，物质滥用和代谢紊乱，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 。

公开(公告)号：WO0073278A2

公开(公告)日：2000-12-07

申请号：PCT/EP0004702

申请日：2000-05-24

Applicant: HOFFMANN LA ROCHE

Inventor： BOES MICHAEL ,  GALLEY GUIDO ,  GODEL THIERRY ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK ,  STADLER HEINZ

IPC: A61K31/505 ,  A61K31/506 ,  A61K31/513 ,  A61K31/5377 ,  A61P1/04 ,  A61P1/08 ,  A61P9/00 ,  A61P11/02 ,  A61P11/06 ,  A61P17/02 ,  A61P25/00 ,  A61P25/06 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D213/00 ,  C07D239/00 ,  C07D239/28 ,  C07D239/34 ,  C07D239/38 ,  C07D239/42 ,  C07D239/46 ,  C07D239/48 ,  C07D295/00 ,  C07D401/04

CPC classification number: C07D239/28 ,  C07D239/34 ,  C07D239/42 ,  C07D239/47 ,  C07D239/48

Abstract: The invention relates to compounds of general formula (I) wherein R is hydrogen or halogen; R is hydrogen, halogen, lower alkyl or lower alkoxy; R is halogen, trifluoromethyl, lower alkoxy or lower alkyl; R /R are independently from each other hydrogen or lower alkyl; R is lower alkyl, lower alkoxy, amino, hydroxy, hydroxy-lower alkyl, -(CH2)n-piperazinyl, optionally substituted by lower alkyl, -(CH2)n-morpholinyl, -(CH2)n+1-imidazolyl, -O-(CH2)n+1-morpholinyl, -O-(CH2)n+1-piperidinyl, lower alkyl-sulfanyl, lower alkyl-sulfonyl, benzylamino, -NH-(CH2)n+1N(R )2, -(CH2)n-NH-(CH2)n+1N(R )2, -(CH2)n+1N(R )2, or -O-(CH2)n+1N(R )2, wherein R is hydrogen or lower alkyl; R is hydrogen; R and R or R and R may be together with the two carbon ring atoms -CH=CH-CH=CH-, with the proviso that n for R is 1; n is independently 0 - 2; and X is -C(O)N(R )- or -N(R )C(O)-; and pharmaceutically acceptable acid addition salts thereof. Compounds of formula (I) have a high affinity to the NK-1 receptor. They are therefore useful for the treatment or diseases which relate to this receptor.

Abstract translation: 本发明涉及通式（I）的化合物，其中R 1是氢或卤素; R 2是氢，卤素，低级烷基或低级烷氧基; R 3是卤素，三氟甲基，低级烷氧基或低级烷基; R 4 / R 4彼此独立地为氢或低级烷基; - （CH 2）n - 吗啉基， - （CH 2）n + 1-烷基， - （CH 2）n - 咪唑基，-O-（CH 2）n + 1-吗啉基，-O-（CH 2）n + 1-哌啶基，低级烷基 - 硫烷基，低级烷基 - 磺酰基，苄基氨基，-NH-（CH 2）n + 4“>）2， - （CH 2）n -NH-（CH 2）n + 1N（R 4”）2， - （CH 2）n + 1N（R 4“）2或-O- CH 2）n + 1N（R 4“）2，其中R 4是氢或低级烷基; R 6是氢; R 2和R 6或R 1和R” 6>可以与两个碳环原子-CH = CH-CH = CH-一起，条件是R 1的n为1; n独立地为0-2;且X为-C（O）N （R 4） - 或-N（R 4）C（O） - 及其药学上可接受的酸加成盐。式（I）化合物对NK-1受体具有高亲和力 因此可用于与该受体相关的治疗或疾病。

公开(公告)号：WO2011057973A9

公开(公告)日：2012-02-02

申请号：PCT/EP2010066960

申请日：2010-11-08

Applicant: HOFFMANN LA ROCHE ,  GALLEY GUIDO ,  NORCROSS ROGER ,  POLARA ALESSANDRA

Inventor： GALLEY GUIDO ,  NORCROSS ROGER ,  POLARA ALESSANDRA

IPC: C07D263/28 ,  A61K31/421 ,  A61K31/422 ,  A61K31/4439 ,  A61K31/506 ,  A61P25/00 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04

CPC classification number: C07D263/28 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04

Abstract: The invention relates to compounds of formula (I) wherein the definitions of X, R and R1 are provided in claim 1. It has now been found that the compounds of formula (I) have a good affinity to the trace amine associated receptors (TAARs), especially for TAARl. 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.

Abstract translation: 本发明涉及式（I）化合物，其中X，R和R 1的定义在权利要求1中提供。现已发现式（I）化合物对微量胺相关受体（TAARs）具有良好的亲和力 ），特别是对于TAARl。 该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，物质滥用和代谢紊乱，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 。