SUBSTITUTED THIOHYDANTOIN DERIVATIVES AS ANDROGEN RECEPTOR ANTAGONISTSDisclosed are compounds, compositions and methods for treating of disorders that are affected by the antagonism of one or more androgen receptor types. Such compounds are represented by Formula (I) as follows: Formula (I) wherein R1 and G are defined herein.A compound of Formula (IFormula (I) whereinRi is chloro, methyl, methoxy, difluoromethyl, or trifluoromethyl;i) ; wherein R4 is selected from the group consisting of bromo, morpholin-2-yl, morpholin-4-yl, morpholin-4-ylmethyl, morpholin-2-ylmethoxy, 5- methylmo holin-2-ylmethoxy, 4,4-difluoropyrrolidin-2-ylmethoxy, (1- methylcarbonyl)-4,4-difluoropyrrolidin-2-ylmethoxy, (l-t-butoxycarbonyl)-4,4- difluoropyrrolidin-2-ylmethoxy, (2-oxa-6-azaspiro[3.3]heptan-6-yl)ethoxy, (6,6- difluoro-2-methyl-2-azaspiro[3.3]heptan-6-yl)ethoxy, 2-oxa-8-azaspiro[4.5]decan- 8-yl)ethoxy, lH-pyrazol-4-yl, lH-pyrazol-3-yl, (l-aminocarbonyl)pyrazol-4-yl, (1- ethylaminocarbonyl)pyrazol-4-yl, methylaminocarbonylmethyl, 2-oxo- imidazolidin-l-yl, (5-methoxymethyl)furan-2-yl, 5-methylfuran-2-yl,tetrahydrofuran-2-yloxy, 4-methylmorpholin-2-yl, l-methylpyrrolidin-3-yloxy, 8- azabicyclo[3.2.1]oct-3-en-3-yl, 8-methyl-8-azabicyclo[3.2.1]oct-3-en-3-yl, 8- azabicyclo[3.2.1]octan-3-yl, 8-methyl-8-azabicyclo[3.2.1]octan-3-yl, 5,8- diazaspiro[2.5]octan-5-ylmethyl, l-azaspiro[3.3]heptan-6-yloxy, 2- azaspiro[3.3]heptan-6-yloxy, 2-azabicyclo[2.2. l]heptan-5-yloxy, (4- aminopiperidin-l-yl)methyl, (2S,3R, 4,S)-3,4-dihydroxy-2-methyl-3,4-dihydro-2H- pyran-6-yl, 3,4-dihydroxy-3,4-dihydro-2H-pyran-6-yl, 2-(hydroxymethyl)-3,4- dihydro-2H-pyran-6-yl, 2-methyl-2-azaspiro[3.3]heptan-6-yl)oxy, 1- methylpiperidin-4-ylcarbonyl, (l-methyl-l-azaspiro[3.3]heptan-6-yl)oxy, (2- methyl-2-azabicyclo[2.2. l]heptan-5-yl)oxy , (3-methyl-3-azaspiro[3.3]heptan-6- yl)oxy, 3-azabicyclo[3.2. l]octan-8-yloxy, (3-t-butoxycarbonyl-3- azaspiro[3.3]heptan-6-yl)oxy, (lR,5,S)-8-azabicyclo[3.2.1]octan-3-yl]oxy, (1- methylazetidin-3-yl)methylaminocarbonyl, l-methylpyrrolidin-3-ylaminocarbonyl, (1 -methyl- 1-oxido-piperi din- l-ium-4-yl)oxy, (3-methyl-3-azabicyclo[3.2.1]octan- 8-yl)oxy, [(lR,55)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl]oxy, (1,2,3,5,6,7,8,8a- octahydroindolizin-7-yl)oxy, 9-azaspiro[3.5]nonan-6-yloxy, (9-methyl-9- azaspiro[3.5]nonan-6-yl)oxy, (l-methylpyrrolidin-3-yl)methylaminocarbonyl, (piperidin-3-yl)methylaminocarbonyl, (4-fluoro-8-azabicyclo[3.2.1]octan-3-yl)oxy, (4-fluoro-8-methyl-8-azabicyclo[3.2.1]octan-3-yl)oxy, (4-fluoro-8-(t- butoxycarbonyl)-8-azabicyclo[3.2.1]octan-3-yl)oxy, (l-methyl-piperidin-4- yl)methylaminocarbonyl, piped din-4-ylmethylaminocarbonyl, (1-methyl-piperidin- 3-yl)methylaminocarbonyl, l-(methyl)piperidin-4-ylmethyl- N(methyl)aminocarbonyl, 1 -(methylaminocarbonyl)piperidin-4- ylmethylaminocarbonyl, 1 -(ethoxycarbonyl)piperidin-4-ylmethylaminocarbonyl, 1 - (t-butoxycarbonyl)piperidin-4-ylmethylaminocarbonyl, 8-(t-butoxycarbonyl)-8- azabicyclo[3.2.1]octan-3-yl, methylaminothiocarbonyl, 3-(t- butoxycarbonylamino)-2,2,4,4-tetramethylcyclobut-l-yloxy, and a substituent selected from a a) , wherein La is absent or -(CH2)r- , wherein r is an integer of 1 or 2; Ra is a substituent selected from methyl, prop-2-yn-l- yl, 2-hydroxyethyl, 2-methoxyethyl, or cyanomethyl; b / b b) R v , wherein V is absent or -OCH2- ; and wherein R is amino, dimethylamino, or t-butoxycarbonyl(N-methyl)amino; , wherein Lc absent or selected from O, S, or -CH2- ; and wherein W is selected from the group consisting of NH, N(methyl); N(cyclopropyl), N(2-hydroxyethyl), N(2-methoxyethyl), N(2-fluoroethyl), N(2,2,2-trifluoroethyl), N(cyanomethyl), N(allyl), N(l-prop-2-ynyl), N(3- fluoropropyl), N(methoxycarbonylmethyl), N(3 -amino-2-hydroxy-prop- 1 - yl), N(3,3-dimethyl-butyl), CH(amino), CH(methylamino),CH(dimethylamino), S, and S02; d) a substituent selected from the group consisting of 2-oxo-piperidin- 4-yloxy, 4-methyl-piperidin-4-yloxy, 1 -methyl-2-trifluoromethyl-piperidin- 4-yloxy, l-methyl-piperidin-3-yloxy, 2-trifluoromethyl-piperidin-4-yloxy, azepan-4-yloxy, azepan-3-yloxy, l-methyl-azepan-4-yloxy, l-methyl-2- oxo-piperidin-4-yloxy, 1 ,4-dimethyl-piperidin-4-yloxy, 2-hydroxymethyl- piperidin-4-yloxy, 2-hydroxymethyl-l-methyl-piperidin-4-yloxy, 3-fluoro- piperidin-4-yloxy, 3-fluoro-l-methyl-piperidin-4-yloxy, 3,3-difluoro- piperidin-4-yloxy, 3 ,3 -difluoro- 1 -methyl-piperidin-4-yloxy, piperazin- 1 - ylmethyl, 4-methyl-piperazin-l-ylmethyl, 3-oxopiperazin-l-ylmethyl, 4- cyclopropyl-piperazin-l-ylmethyl, 3 -hydroxymethyl-piperazin-1 -ylmethyl, 4-(2-hydroxyethyl)piperazin- 1 -ylmethyl, 4-(methylaminocarbonyl)piperazin- 1 -ylmethyl, 4-(ethoxycarbonyl)piperazin- 1 -yl, 4-(ethoxycarbonyl)piperazin- 1 -ylmethyl, 4-(ethoxycarbonyl)piperazin- 1-ylcarbonyl, 4-(pyrrolidin-l-ylcarbonyl)piperazin-l-yl, 4-(t- butoxycarbonyl)piperazin- 1 -ylmethyl, and 4-(t-butoxycarbonyl)piperazin- 1 - ylcarbonyl; and R is hydrogen, fluoro, or methoxy; provided that when R4 is bromo, R3 is hydrogen or methoxy;0—( NHprovided that when R4 is — f , R1 is chloro, methoxy, or difluoromethyl;O—L N—provided that when R4 is — / and R3 is hydrogen or fluoro, R1 is chloro, methoxy, or difluoromethyl; provided that when R4 is R3 is hydrogen, R1 is chloro, methoxy, or difluoromethyl; provided that when R4 is...
안드로겐 수용체 길항제로서의 치환된 티오히단토인 유도체하나 이상의 안드로겐 수용체 타입의 길항작용에 의해 영향을 받는 장애를 치료하기 위한 화합물, 조성물 및 방법이 개시된다. 이러한 화합물은 다음과 같이 화학식 (I)으로 나타낸다: [화학식 (I)] 상기 식에서, R1 및 G는 본 명세서 및 청구범위에서 정의된 바와 같다.화학식 (I)의 화합물, 또는 이의 거울상 이성질체, 부분입체 이성질체 또는 약제학적으로 허용가능한 염 형태: [화학식 (I)]상기 식에서,R1은 클로로, 메틸, 메톡시, 다이플루오로메틸 또는 트라이플루오로메틸이고;G는,i)  - 여기서, R4는 브로모, 모르폴린-2-일, 모르폴린-4-일, 모르폴린-4-일메틸, 모르폴린-2-일메톡시, 5-메틸모르폴린-2-일메톡시, 4,4-다이플루오로피롤리딘-2-일메톡시, (1-메틸카르보닐)-4,4-다이플루오로피롤리딘-2-일메톡시, (1-t-부톡시카르보닐)-4,4-다이플루오로피롤리딘-2-일메톡시, (2-옥사-6-아자스피로[3.3]헵탄-6-일)에톡시, (6,6-다이플루오로-2-메틸-2-아자스피로[3.3]헵탄-6-일)에톡시, 2-옥사-8-아자스피로[4.5]데칸-8-일)에톡시, 1H-피라졸-4-일, 1H-피라졸-3-일, (1-아미노카르보닐)피라졸-4-일, (1-에틸아미노카르보닐)피라졸-4-일, 메틸아미노카르보닐메틸, 2-옥소-이미다졸리딘-1-일, (5-메톡시메틸)푸란-2-일, 5-메틸푸란-2-일, 테트라하이드로푸란-2-일옥시, 4-메틸모르폴린-2-일, 1-메틸피롤리딘-3-일옥시, 8-아자바이사이클로[3.2.1]옥트-3-엔-3-일, 8-메틸-8-아자바이사이클로[3.2.1]옥트-3-엔-3-일, 8-아자바이사이클로[3.2.1]옥탄-3-일, 8-메틸-8-아자바이사이클로[3.2.1]옥탄-3-일, 5,8-다이아자스피로[2.5]옥탄-5-일메틸, 1-아자스피로[3.3]헵탄-6-일옥시, 2-아자스피로[3.3]헵탄-6-일옥시, 2-아자바이사이클로[2.2.1]헵탄-5-일옥시, (4-아미노피페리딘-1-일)메틸, (2S,3R,4S)-3,4-다이하이드록시-2-메틸-3,4-다이하이드로-2H-피란-6-일, 3,4-다이하이드록시-3,4-다이하이드로-2H-피란-6-일, 2-(하이드록시메틸)-3,4-다이하이드로-2H-피란-6-일, 2-메틸-2-아자스피로[3.3]헵탄-6-일)옥시, 1-메틸피페리딘-4-일카르보닐, (1-메틸-1-아자스피로[3.3]헵탄-6-일)옥시, (2-메틸-2-아자바이사이클로[2.2.1]헵탄-5-일)옥시, (3-메틸-3-아자스피로[3.3]헵탄-6-일)옥시, 3-아자바이사이클로[3.2.1]옥탄-8-일옥시, (3-t-부톡시카르보닐-3-아자스피로[3.3]헵탄-6-일)옥시, (1R,5S)-8-아자바이사이클로[3.2.1]옥탄-3-일]옥시, (1-메틸아제티딘-3-일)메틸아미노카르보닐, 1-메틸피롤리딘-3-일아미노카르보닐, (1-메틸-1-옥시도-피페리딘-1-윰-4-일)옥시, (3-메틸-3-아자바이사이클로[3.2.1]옥탄-8-일)옥시, [(1R,5S)-8-메틸-8-아자바이사이클로[3.2.1]옥탄-3-일]옥시, (1,2,3,5,6,7,8,8a-옥타하이드로인돌리진-7-일)옥시, 9-아자스피로[3.5]노난-6-일옥시, (9-메틸-9-아자스피로[3.5]노난-6-일)옥시, (1-메틸피롤리딘-3-일)메틸아미노카르보닐, (피페리딘-3-일)메틸아미노카르보닐, (4-플루오로-8-아자바이사이클로[3.2.1]옥탄-3-일)옥시, (4-플루오로-8-메틸-8-아자바이사이클로[3.2.1]옥탄-3-일)옥시, (4-플루오로-8-(t-부톡시카르보닐)-8-아자바이사이클로[3.2.1]옥탄-3-일)옥시, (1-메틸-피페리딘-4-일)메틸아미노카르보닐, 피페리딘-4-일메틸아미노카르보닐, (1-메틸-피페리딘-3-일)메틸아미노카르보닐, 1-(메틸)피페리딘-4-일메틸-N(메틸)아미노카르보닐, 1-(메틸아미노카르보닐)피페리딘-4-일메틸아미노카르보닐, 1-(에톡시카르보닐)피페리딘-4-일메틸아미노카르보닐, 1-(t-부톡시카르보닐)피페리딘-4-일메틸아미노카르보닐, 8-(t-부톡시카르보닐)-8-아자바이사이클로[3.2.1]옥탄-3-일, 메틸아미노티오카르보닐, 3-(t-부톡시카르보닐아미노)-2,2,4,4-테트라메틸사이클로부트-1-일옥시, 및 a) 내지 e)로부터 선택되는 치환기:a)  {여기서, La는 존재하지 않거나 -(CH2)r- (여기서, r은 1 또는 2의 정수임)이고; Ra는 메틸, 프로프-2-인-1-일, 2-하이드록시에틸, 2-메톡시에틸 또는 시아노메틸로부터 선택되는 치환기임};b)  (여기서, V는 존재하지 않거나 -OCH2-이고; Rb는 아미노, 다이메틸아미노 또는 t-부톡시카르보닐(N-메틸)아미노임);c)  (여기서, Lc는 존재하지 않거나, O, S 또는 -CH2-로부터 선택되고; W는 NH, N(메틸), N(사이클로프로필), N(2-하이드록시에틸), N(2-메톡시에틸), N(2-플루오로에틸), N(2,2,2-트라이플루오로에틸), N(시아노메틸), N(알릴), N(1-프로프-2-이닐), N(3-플루오로프로필), N(메톡시카르보닐메틸), N(3-아미노-2-하이드록시-프로프-1-일), N(3,3-다이메틸-부틸), CH(아미노), CH(메틸아미노), CH(다이메틸아미노), S 및 SO2로 이루어진 군으로부터 선택됨);d) 2-옥소-피페리딘-4-일옥시, 4-메틸-피페리딘-4-일옥시, 1-메틸-2-트라이플루오로메틸-피페리딘-4-일옥시, 1-메틸-피페리딘-3-일옥시, 2-트라이플루오로메틸-피페리딘-4-일옥시, 아제판-4-일옥시, 아제판-3-일옥시, 1-메틸-아제판-4-일옥시, 1-메틸-2-옥소-피페리딘-4-일옥시, 1,4-다이메틸-피페리딘-4-일옥시, 2-하이드록시메틸-피페리딘-4-일옥시, 2-하이드록시메틸-1-메틸-피페리딘-4-일옥시, 3-플루오로-피페리딘-4-일옥시, 3-플루오로-1-메틸-피페리딘-4-일옥시, 3,3-다이플루오로-피페리딘-4-일옥시, 3,3-다이플루오로-1-메틸-피페리딘-4-일옥시, 피페라진-1-일메틸, 4-메틸-피페라진-1-일메틸, 3-옥소피페라진-1-일메틸, 4-사이클로프로필-피페라진-1-일메틸, 3-하이드록시메틸-피페라진-1-일메틸, 4-(2-하이드록시에틸)피페라진-1-일메틸, 4-(메틸아미노카르보닐)피페라진-1-일메틸, 4-(에톡시카르보닐)피페라진-1-일, 4-(에톡시카르보닐)피페라진-1-일메틸, 4-(에톡시카르보닐)피페라진-1-일카르보닐, 4-(피롤리딘-1-일카르보닐)피페라진-1-일, 4-(t-부톡시카르보닐)피페라진-1-일메틸 및 4-(t-부톡시카르보닐)피페라진-1-일카르보닐로 이루어진 군으로부터 선택되는 치환기로 이루어진 군으로부터 선택되고; R3는 수소, 플루오로 또는 메톡시이되; 단, R4가 브로모이면, R3는 수소 또는 메톡시이고; R4가 이면, R1은 클로로, 메톡시 또는 다이플루오로메틸이며;R4가 이고, R3가 수소 또는 플루오로이면, R1은 클로로, 메톡시 또는 다이플루오로메틸이며; R4가 이고, R3가 수소이면, R1은 클로로, 메톡시 또는 다이플루오로메틸이며; R4가  또는 이고, R3가 수소이면, R1은 클로로, 메톡시, 다이플루오로메틸 또는 트라이플루오로메틸이며; R4가 이고, R3가 수소이면, R1은 클로로, 메틸, 메톡시 또는 다이플루오로메틸임 -; ii)  - 여기서, R7은 하이드록시, 메톡시, 시아노메틸, 1,4-(다이메틸)피페리딘-4-일)옥시, 테트라하이드로-2H-티오피란-4-일옥시, 아미노설포닐, 2-아자바이사이클로[2.2.1]헵탄-5-일옥시, 2-메틸-2-아자바이사이클로[2.2.1]헵탄-5-일옥시, (3-메틸-3-아자스피로[3.3]헵탄-6-일)옥시, 3-아자바이사이클로[3.2.1]옥탄-8-일옥시, (3-메틸-3-아자바이사이클로[3.2.1]옥탄-8-일)옥시, 9-아자스피로[3.5]노난-6-일옥시, (9-메틸-9-아자스피로[3.5]노난-6-일)옥시, 4-(에톡시카르보닐)피페라진-1-일, 3-(다이메틸아미노)프로필옥시, 3-(t-부톡시카르보닐)-3-아자스피로[3.3]헵탄-6-일옥시 및 치환기 f) f)(여기서, Wf는 NH, N(메틸), N(2-하이드록시에틸), N(2-메톡시에틸), N(2-플루오로에틸), N(2,2,2-트라이플루오로에틸), N(시아노메틸), N(알릴), N(아이소펜틸), N(프로프-2-인-1-일), N(3,3-다이메틸부틸), N(3-플루오로프로필), N(3,3,3-트라이플루오로프로필), N(메톡시카르보닐메틸), N(3-아미노-2-하이드록시-프로필), N(3,3-다이메틸-부틸), CH(아미노), CH(메틸아미노), CH(다이메틸아미노), S 및 SO2로 이루어진 군으로부터 선택됨)로 이루어진 군으로부터 선택됨 -; iii) 인다졸-5-일, 인다졸-6-일, 벤즈이미다졸-5-일, 인돌-5-일 및 인돌-6-일로 이루어진 군으로부터 선택되는 헤테로아릴 - 여기서, 상기 헤테로아릴은 임의로 독립적으로, 상기 헤테로아릴의 질소 함유 부분에서 메틸, 2-하이드록시에틸, 2-메톡시에틸, 피페리딘-4-일, 1-(메틸)피페리딘-4-일, 1-(메틸카르보닐)피페리딘-4-일, 1-(t-부톡시카르보닐)피페리딘-4-일, 피페리딘-4-일메틸, 1-(메틸카르보닐)피페리딘-4-일메틸, 1-메틸-피페리딘-4-일메틸 또는 1-(t-부톡시카르보닐)피페리딘-4-일메틸로부터 선택되는 치환기로 치환되고;iii)의 상기 헤테로아릴은 임의로 추가로, 추가의 메틸 치환기로 치환되되;단, G가 1-메틸-2-(1-메틸-피페리딘-4-일)벤즈이미다졸-5-일, 1-메틸-2-(피페리딘-4-일)벤즈이미다졸-5-일, 비치환된 인다졸-5-일 또는 비치환된 인다졸-6-일로부터 선택되면, R1은 클로로, 메틸, 메톡시 또는 다이플루오로메틸임 -;iv)  - 여기서, R8은 수소, 메틸, 사이클로프로필, 2-하이드록시에틸, 2-메톡시에틸, 2-플루오로에틸, 2,2,2-트라이플루오로에틸, 시아노메틸, 알릴, 1-프로프-2-이닐, 3-플루오로프로필, 메톡시카르보닐메틸, 3-아미노-2-하이드록시-프로필 및 3,3-다이메틸-부틸로 이루어진 군으로부터 선택됨 -; v) 2-(R9)-1,2,3,4-테트라하이드로아이소퀴놀린-6-일 - 여기서, R9은 수소, 메틸, 메틸카르보닐 및 t-부톡시카르보닐로 이루어진 군으로부터 선택됨 -;vi)  - 여기서, R11은 메틸 또는 1-(t-부톡시카르보닐)-아제티딘-3-일메틸임 -; 또는vii)  - 여기서, R10은 메톡시카르보닐, 페닐옥시 및 페닐카르보닐아미노로 이루어진 군으로부터 선택됨 - 이며; 여기서, G의 어떤 질소 함유 헤테로사이클릭 치환기라도 임의로 옥시도 치환기로 치환.