ARYL KETONE AS MRIThis invention pertains to aryl pyrrolidinyl and piperidinyl ketone compounds of formula (I) wherein R1 and R2 are as described herein, as well as pharmaceutically acceptable salts and esters thereof, and methods for using the same. In particular, compounds of the present invention are useful for treatment of diseases associated with monoamine reuptake inhibition.A compound of formula I :OR Jk Rwherein:R is: 4-chloro-3-methyl-phenyl;2-amino-3,4-dichloro-phenyl);3 ,4-dichloro-phenyl;4-chloro-3-(3,3-dimethyl-butoxy)-phenyl;3-benzyloxy-4-chloro-phenyl;7-fluoro- lH-indol-5-yl;4-amino-3-chloro-5-trifluoromethyl-phenyl;4-chloro-3-(4-fluoro-phenoxy)-phenyl;4-chloro-3-(2-fluoro-phenoxy)-phenyl;3-benzyloxy-4-chloro-phenyl;4-chloro-3-(3,3-dimethyl-butoxy)-phenyl;4-chloro-2-phenoxy-phenyl;4-chloro-3-(tetrahydro-pyran-4-ylmethoxy)-phenyl;4-chloro-3-trifluoromethoxy-phenyl;4-chloro-3-phenylsulfanyl-phenyl;3-benzenesulfonyl-4-chloro-phenyl;4-chloro-3-(2-fluoro-phenoxy)-phenyl;4-chloro-3-(4-fluoro-phenoxy)-phenyl;4-chloro-3-phenoxy-phenyl;4-bromo-3-phenoxy-phenyl;4-amino-3-chloro-5-fluoro-phenyl;4-amino-3-chloro-phenyl;4-chloro-3-(4-trifluoromethyl-phenoxy)-phenyl;3-chloro-4-methyl-phenyl; naphthalen-2-yl;4-chloro-2-phenoxy-phenyl; phenyl;3-chloro-4-methylamino-phenyl;4-chloro-3-phenoxy-phenyl;4-chloro-3 -(2/f-pyrazo 1-3 -yl)-phenyl; 4-chloro-3-(methyl-phenyl-amino)-phenyl; lH-Indol-5-yl;4-chloro-3-pyridin-3-yl-phenyl; 3-bromo-4-imidazol-l-yl-phenyl; or 4-chloro-3-imidazol- 1 -yl-phenyl;R2 is: 3-(3,3-dimethyl-butyl)-pyrrolidin-3-yl; (R)-3 -isobutyl-pyrro lidin-3 -yl; (lR,2S,4S)-2-butyl-7-aza-bicyclo[2.2.1]hept-2-yl; 3 -(2-methoxy-2-methyl-propyl)-pyrro lidin-3 -yl; 3 -propyl-pyrro lidin-3 -yl; 3 -isobutyl-pyrro lidin-3 -yl; 3 -ethyl-pyrro lidin-3 -yl; (R)-3 -(3-methyl-butyl)-pyrro lidin-3 -yl; (S)-3-(3-methyl-butyl)-pyrrolidin-3-yl; (S)-3-isobutyl-pyrrolidin-3-yl; (S)-3-(3,3-dimethyl-butyl)-pyrrolidin-3-yl; (R)-3 -(3 ,3 -dimethyl-butyl)-pyrro lidin-3 -yl; (S)-3-propyl-pyrrolidin-3-yl; (R)-3-propyl-pyrrolidin-3-yl;(R)-2-propyl-pyrrolidin-2-yl)-methanone;4-( 1 -methyl-cyclopropylmethyl)-piperidin-4-yl;4-isobutyl-piperidin-4-yl;4-propyl-piperidin-4-yl;4-(2-methoxy-2-methyl-propyl)-piperidin-4-yl;4-(3-methyl-butyl)-piperidin-4-yl;4-cyclopentylmethyl-piperidin-4-yl;4-(tetrahydro-pyran-4-ylmethyl)-piperidin-4-yl;4-(tetrahydro-furan-2-ylmethyl)-piperidin-4-yl;4-(3,4-Dichloro-benzyl)-piperidin-4-yl;(lR,2S,5R)-2-isobutyl-8-aza-bicyclo[3.2.1]oct-2-yl;(lR,2R,5R)-2-ethyl-8-aza-bicyclo[3.2.1]oct-2-yl;(lR,2S,5R)-2-ethyl-8-aza-bicyclo[3.2.1]oct-2-yl;3 -propyl-piperidin-3 -yl;(lR,2R,5R)-2-propyl-8-aza-bicyclo[3.2. l]oct-2-yl;(lR,2R,5R)-2-ethyl-8-methyl-8-aza-bicyclo[3.2.1]oct-2-yl;(lR,2R,5R)-2-butyl-8-methyl-8-aza-bicyclo[3.2.1]oct-2-yl;3-(3,3-dimethyl-butyl)-piperidin-3-yl; (S)-3-(3,3-dimethyl-butyl)-piperidin-3-yl; or(R)-3 -(3 ,3 -dimethyl-butyl)-piperidin-3 -yl] -methanone;and wherein said compound is selected from the group consisting of:(4-Chloro-3-methyl-phenyl)-[3-(3,3-dimethyl-butyl)-pyrrolidin-3-yl]-methanone;(2-Amino-3,4-dichloro-phenyl)-((R)-3-isobutyl-pyrrolidin-3-yl)-methanone;((lR,2S,4S)-2-Butyl-7-aza-bicyclo[2.2.1]hept-2-yl)-(3,4-dichloro-phenyl)-methanone;[4-Chloro-3-(3,3-dimethyl-butoxy)-phenyl]-[3-(3,3-dimethyl-butyl)-pyrrolidin-3-yl]- methanone;(3-Benzyloxy-4-chloro-phenyl)-[3-(3,3-dimethyl-butyl)-pyrrolidin-3-yl]-methanone;(7-Fluoro- lH-indo 1-5 -yl)- [3 -(2-methoxy-2-methyl-propyl)-pyrro lidin-3 -yl] -methanone;(4- Amino-3 -chloro-5-trifluoromethyl-phenyl)- [3 -(3 ,3 -dimethyl-butyl)-pyrro lidin-3 -yl] - methanone;[4-Chloro-3-(4-fluoro-phenoxy)-phenyl]-[3-(3,3-dimethyl-butyl)-pyrrolidin-3-yl]- methanone;[4-Chloro-3-(2-fluoro-phenoxy)-phenyl]-[3-(3,3-dimethyl-butyl)-pyrrolidin-3-yl]- methanone;(3-Benzyloxy-4-chloro-phenyl)-(3-propyl-pyrrolidin-3-yl)-methanone;[4-Chloro-3-(3,3-dimethyl-butoxy)-phenyl]-(3-propyl-pyrrolidin-3-yl)-methanone;(4-Chloro-2-phenoxy-phenyl)-(3-isobutyl-pyrrolidin-3-yl)-methanone;[4-Chloro-3-(tetrahydro-pyran-4-ylmethoxy)-phenyl]-(3-propyl-pyrrolidin-3-yl)- methanone;(4-Chloro-3-trifluoromethoxy-phenyl)-(3-propyl-pyrrolidin-3-yl)-methanone;(4-Chloro-3-phenylsulfanyl-phenyl)-(3-propyl-pyrrolidin-3-yl)-methanone;(3-Benzenesulfonyl-4-chloro-phenyl)-(3-propyl-pyrrolidin-3-yl)-methanone;[4-Chloro-3-(2-fluoro-phenoxy)-phenyl]-(3-propyl-pyrrolidin-3-yl)-methanone;[4-Chloro-3-(4-fluoro-phenoxy)-phenyl]-(3-propyl-pyrrolidin-3-yl)-methanone;(4-Chloro-3-phenoxy-phenyl)-(3-ethyl-pyrrolidin-3-yl)-methanone;(4-Bromo-3-phenoxy-phenyl)-(3-propyl-pyrrolidin-3-yl)-methanone;(4- Amino-3 -chloro-5-fluoro-phenyl)- [(R)-3 -(3 -methyl-butyl)-pyrro lidin-3 -yl] -methanone;(4- Amino-3 -chloro-5-fluoro-phenyl)- [(S)-3 -(3 -methyl-butyl)-pyrro lidin-3 -yl] -methanone;(4-Amino-3-chloro-5-fluoro-phenyl)-((S)-3-isobutyl-pyrrolidin-3-yl)-methanone;(4-Amino-3-chloro-5-fluoro-phenyl)-((R)-3-isobutyl-pyrrolidin-3-yl)-methanone;(4-Amino-3-chloro-5-fluoro-phenyl)-[(S)-3-(3,3-dimethyl-butyl)-pyrrolidin-3-yl]- methanone;(4- Amino-3 -chloro-5-fluoro-phenyl)- [(R)-3 -(3 ,3 -dimethyl-butyl)-pyrro lidin-3 -yl] - methanone;(4-Amino-3-chloro-phenyl)-((R)-3-isobutyl-pyrrolidin-3-yl)-methanone; (4-Amino-3-chloro-phenyl)-((S)-3-isobutyl-pyrrolidin-3-yl)-methanone;(4-Chloro-3-phenoxy-phenyl)-((S)-3-propyl-pyrrolidin-3-yl)-methanone;(4-Chloro-3-phenoxy-phenyl)-((R)-3-propyl-pyrrolidin-3-yl)-methanon...
ＭＲＩ로서의 아릴 케톤본 발명은 하기 화학식 I의 아릴 피롤리디닐 및 피페리디닐 케톤 화합물 또는 이의 약학적으로 허용가능한 염 및 에스터, 및 이의 사용 방법에 관한 것이다: 화학식 I 상기 식에서, R1 및 R2는 본원에 기재된 바와 같다. 특히, 본 발명의 화합물은 모노아민 재흡수 억제와 관련된 질병의 치료에 유용하다.하기 화학식 I의 화합물:[화학식 I]상기 식에서,R1은, 4-클로로-3-메틸-페닐;2-아미노-3,4-다이클로로-페닐;3,4-다이클로로-페닐;4-클로로-3-(3,3-다이메틸-부톡시)-페닐;3-벤질옥시-4-클로로-페닐;7-플루오로-1H-인돌-5-일;4-아미노-3-클로로-5-트라이플루오로메틸-페닐;4-클로로-3-(4-플루오로-페녹시)-페닐;4-클로로-3-(2-플루오로-페녹시)-페닐;3-벤질옥시-4-클로로-페닐;4-클로로-3-(3,3-다이메틸-부톡시)-페닐;4-클로로-2-페녹시-페닐;4-클로로-3-(테트라하이드로-피란-4-일메톡시)-페닐;4-클로로-3-트라이플루오로메톡시-페닐;4-클로로-3-페닐설파닐-페닐;3-벤젠설포닐-4-클로로-페닐;4-클로로-3-(2-플루오로-페녹시)-페닐;4-클로로-3-(4-플루오로-페녹시)-페닐;4-클로로-3-페녹시-페닐;4-브로모-3-페녹시-페닐;4-아미노-3-클로로-5-플루오로-페닐;4-아미노-3-클로로-페닐;4-클로로-3-(4-트라이플루오로메틸-페녹시)-페닐;3-클로로-4-메틸-페닐;나프탈렌-2-일;4-클로로-2-페녹시-페닐;페닐;3-클로로-4-메틸아미노-페닐;4-클로로-3-페녹시-페닐;4-클로로-3-(2H-피라졸-3-일)-페닐;4-클로로-3-(메틸-페닐-아미노)-페닐;1H-인돌-5-일;4-클로로-3-피리딘-3-일-페닐;3-브로모-4-이미다졸-1-일-페닐; 또는4-클로로-3-이미다졸-1-일-페닐이고;R2는, 3-(3,3-다이메틸-부틸)-피롤리딘-3-일;(R)-3-아이소부틸-피롤리딘-3-일;(1R,2S,4S)-2-부틸-7-아자-바이사이클로[2.2.1]헵트-2-일;3-(2-메톡시-2-메틸-프로필)-피롤리딘-3-일;3-프로필-피롤리딘-3-일;3-아이소부틸-피롤리딘-3-일;3-에틸-피롤리딘-3-일;(R)-3-(3-메틸-부틸)-피롤리딘-3-일;(S)-3-(3-메틸-부틸)-피롤리딘-3-일;(S)-3-아이소부틸-피롤리딘-3-일;(S)-3-(3,3-다이메틸-부틸)-피롤리딘-3-일;(R)-3-(3,3-다이메틸-부틸)-피롤리딘-3-일;(S)-3-프로필-피롤리딘-3-일;(R)-3-프로필-피롤리딘-3-일;(R)-2-프로필-피롤리딘-2-일)-메탄온;4-(1-메틸-사이클로프로필메틸)-피페리딘-4-일;4-아이소부틸-피페리딘-4-일;4-프로필-피페리딘-4-일;4-(2-메톡시-2-메틸-프로필)-피페리딘-4-일;4-(3-메틸-부틸)-피페리딘-4-일;4-사이클로펜틸메틸-피페리딘-4-일;4-(테트라하이드로-피란-4-일메틸)-피페리딘-4-일;4-(테트라하이드로-푸란-2-일메틸)-피페리딘-4-일;4-(3,4-다이클로로-벤질)-피페리딘-4-일;(1R,2S,5R)-2-아이소부틸-8-아자-바이사이클로[3.2.1]옥트-2-일;(1R,2R,5R)-2-에틸-8-아자-바이사이클로[3.2.1]옥트-2-일;(1R,2S,5R)-2-에틸-8-아자-바이사이클로[3.2.1]옥트-2-일;3-프로필-피페리딘-3-일;(1R,2R,5R)-2-프로필-8-아자-바이사이클로[3.2.1]옥트-2-일;(1R,2R,5R)-2-에틸-8-메틸-8-아자-바이사이클로[3.2.1]옥트-2-일;(1R,2R,5R)-2-부틸-8-메틸-8-아자-바이사이클로[3.2.1]옥트-2-일;3-(3,3-다이메틸-부틸)-피페리딘-3-일;(S)-3-(3,3-다이메틸-부틸)-피페리딘-3-일; 또는(R)-3-(3,3-다이메틸-부틸)-피페리딘-3-일]-메탄온이고;상기 화합물은 하기 화합물들로 이루어진 군으로부터 선택된다:(4-클로로-3-메틸-페닐)-[3-(3,3-다이메틸-부틸)-피롤리딘-3-일]-메탄온;(2-아미노-3,4-다이클로로-페닐)-((R)-3-아이소부틸-피롤리딘-3-일)-메탄온;((1R,2S,4S)-2-부틸-7-아자-바이사이클로[2.2.1]헵트-2-일)-(3,4-다이클로로-페닐)-메탄온;[4-클로로-3-(3,3-다이메틸-부톡시)-페닐]-[3-(3,3-다이메틸-부틸)-피롤리딘-3-일]-메탄온;(3-벤질옥시-4-클로로-페닐)-[3-(3,3-다이메틸-부틸)-피롤리딘-3-일]-메탄온;(7-플루오로-1H-인돌-5-일)-[3-(2-메톡시-2-메틸-프로필)-피롤리딘-3-일]-메탄온;(4-아미노-3-클로로-5-트라이플루오로메틸-페닐)-[3-(3,3-다이메틸-부틸)-피롤리딘-3-일]-메탄온;[4-클로로-3-(4-플루오로-페녹시)-페닐]-[3-(3,3-다이메틸-부틸)-피롤리딘-3-일]-메탄온;[4-클로로-3-(2-플루오로-페녹시)-페닐]-[3-(3,3-다이메틸-부틸)-피롤리딘-3-일]-메탄온;(3-벤질옥시-4-클로로-페닐)-(3-프로필-피롤리딘-3-일)-메탄온;[4-클로로-3-(3,3-다이메틸-부톡시)-페닐]-(3-프로필-피롤리딘-3-일)-메탄온;(4-클로로-2-페녹시-페닐)-(3-아이소부틸-피롤리딘-3-일)-메탄온;[4-클로로-3-(테트라하이드로-피란-4-일메톡시)-페닐]-(3-프로필-피롤리딘-3-일)-메탄온;(4-클로로-3-트라이플루오로메톡시-페닐)-(3-프로필-피롤리딘-3-일)-메탄온;(4-클로로-3-페닐설파닐-페닐)-(3-프로필-피롤리딘-3-일)-메탄온;(3-벤젠설포닐-4-클로로-페닐)-(3-프로필-피롤리딘-3-일)-메탄온;[4-클로로-3-(2-플루오로-페녹시)-페닐]-(3-프로필-피롤리딘-3-일)-메탄온;[4-클로로-3-(4-플루오로-페녹시)-페닐]-(3-프로필-피롤리딘-3-일)-메탄온;(4-클로로-3-페녹시-페닐)-(3-에틸-피롤리딘-3-일)-메탄온;(4-브로모-3-페녹시-페닐)-(3-프로필-피롤리딘-3-일)-메탄온;(4-아미노-3-클로로-5-플루오로-페닐)-[(R)-3-(3-메틸-부틸)-피롤리딘-3-일]-메탄온;(4-아미노-3-클로로-5-플루오로-페닐)-[(S)-3-(3-메틸-부틸)-피롤리딘-3-일]-메탄온;(4-아미노-3-클로로-5-플루오로-페닐)-((S)-3-아이소부틸-피롤리딘-3-일)-메탄온;(4-아미노-3-클로로-5-플루오로-페닐)-((R)-3-아이소부틸-피롤리딘-3-일)-메탄온;(4-아미노-3-클로로-5-플루오로-페닐)-[(S)-3-(3,3-다이메틸-부틸)-피롤리딘-3-일]-메탄온;(4-아미노-3-클로로-5-플루오로-페닐)-[(R)-3-(3,3-다이메틸-부틸)-피롤리딘-3-일]-메탄온;(4-아미노-3-클로로-페닐)-((R)-3-아이소부틸-피롤리딘-3-일)-메탄온;(4-아미노-3-클로로-페닐)-((S)-3-아이소부틸-피롤리딘-3-일)-메탄온;(4-클로로-3-페녹시-페닐)-((S)-3-프로필-피롤리딘-3-일)-메탄온;(4-클로로-3-페녹시-페닐)-((R)-3-프로필-피롤리딘-3-일)-메탄온;(4-클로로-3-페녹시-페닐)-(3-아이소부틸-피롤리딘-3-일)-메탄온;[4-클로로-3-(4-트라이플루오로메틸-페녹시)-페닐]-(3-프로필-피롤리딘-3-일)-메탄온;(4-클로로-3-페녹시-페닐)-((R)-2-프로필-피롤리딘-2-일)-메탄온;(3,4-다이클로로-페닐)-[4-(1-메틸-사이클로프로필메틸)-피페리딘-4-일]-메탄온;(3-클로로-4-메틸-페닐)-(4-아이소부틸-피페리딘-4-일)-메탄온;나프탈렌-2-일-(4-프로필-피페리딘-4-일)-메탄온;(3,4-다이클로로-페닐)-[4-(2-메톡시-2-메틸-프로필)-피페리딘-4-일]-메탄온;(3-클로로-4-메틸-페닐)-[4-(3-메틸-부틸)-피페리딘-4-일]-메탄온;(4-사이클로펜틸메틸-피페리딘-4-일)-(3,4-다이클로로-페닐)-메탄온;(4-클로로-2-페녹시-페닐)-(4-프로필-피페리딘-4-일)-메탄온;(3,4-다이클로로-페닐)-[4-(테트라하이드로-피란-4-일메틸)-피페리딘-4-일]-메탄온;(3,4-다이클로로-페닐)-[4-(테트라하이드로-푸란-2-일메틸)-피페리딘-4-일]-메탄온;[4-(3,4-다이클로로-벤질)-피페리딘-4-일]-페닐-메탄온;(3-클로로-4-메틸아미노-페닐)-(4-아이소부틸-피페리딘-4-일)-메탄온;(4-클로로-3-페녹시-페닐)-(4-아이소부틸-피페리딘-4-일)-메탄온;(4-클로로-3-페녹시-페닐)-(4-프로필-피페리딘-4-일)-메탄온;(3,4-다이클로로-페닐)-((1R,2S,5R)-2-아이소부틸-8-아자-바이사이클로[3.2.1]옥트-2-일)-메탄온;(3,4-다이클로로-페닐)-((1R,2R,5R)-2-에틸-8-아자-바이사이클로[3.2.1]옥트-2-일)-메탄온;(3,4-다이클로로-페닐)-((1R,2S,5R)-2-에틸-8-아자-바이사이클로[3.2.1]옥트-2-일)-메탄온;[4-클로로-3-(2H-피라졸-3-일)-페닐]-(3-프로필-피페리딘-3-일)-메탄온;[4-클로로-3-(메틸-페닐-아미노)-페닐]-(3-프로필-피페리딘-3-일)-메탄온;(1H-인돌-5-일)-((1R,2R,5R)-2-프로필-8-아자-바이사이클로[3.2.1]옥트-2-일)-메탄온;(3,4-다이클로로-페닐)-((1R,2R,5R)-2-에틸-8-메틸-8-아자-바이사이클로[3.2.1]옥트-2-일)-메탄온;((1R,2R,5R)-2-부틸-8-메틸-8-아자-바이사이클로[3.2.1]옥트-2-일)-(3,4-다이클로로-페닐)-메탄온;(4-클로로-3-피리딘-3-일-페닐)-(3-프로필-피페리딘-3-일)-메탄온;(3,4-다이클로로-페닐)-[3-(3,3-다이메틸-부틸)-피페리딘-3-일]-메탄온;(3-브로모-4-이미다졸-1-일-페닐)-(3-프로필-피페리딘-3-일)-메탄온;(4-클로로-3-이미다졸-1-일-페닐)-(3-프로필-피페리딘-3-일)-메탄온;(3,4-다이클로로-페닐)-[(S)-3-(3,3-다이메틸-부틸)-피페리딘-3-일]-메탄온; 및(3,4-다이클로로-페닐)-[(R)-3-(3,3-다이메틸-부틸)-피페리딘-3-일]-메탄온.