Compounds which inhibit BETA-SECRETASE activity and methods of use thereofThe present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease.Compound, this compound is:n1-((2s, 3r)-4-((5-(2-fluoropropane-2-yl) pyridin-3-yl) methylamino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-3-hydroxyl-4-((3-methoxy-benzyl) (methyl) amino)-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(3-(dimethylamino) benzylamino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(3-fluoro-5-(trifluoromethyl) benzylamino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(2-fluoro-6-methoxy-benzyl amino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(the 3-tertiary butyl-2-hydroxybenzyl amino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(the 5-tertiary butyl-2-hydroxybenzyl amino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(3-ethanoyl benzylamino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(3,5-dimethoxy-benzyl amino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(3,4-dimethyl benzyl amino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(3, two (trifluoromethyl) benzylaminos of 5-)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;3-(((2r, 3s)-2-hydroxyl-3-(3-(methyl ((4-methylthiazol-2-yl) methyl) carbamyl) benzamido)-4-phenyl butyl amino) methyl)-the 5-methoxyl methyl benzoate;3-(((2r, 3s)-2-hydroxyl-3-(3-(methyl ((4-methylthiazol-2-yl) methyl) carbamyl) benzamido)-4-phenyl butyl amino) methyl)-the 5-methoxybenzoic acid;n1-((2s, 3r)-3-hydroxyl-4-(3-iodine benzylamino)-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(3-benzyl chloride base amino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-3-hydroxyl-4-(3-methoxyl group-5-(methyl carbamyl) benzylamino)-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;3-(((2r, 3s)-2-hydroxyl-3-(3-(methyl ((4-methylthiazol-2-yl) methyl) carbamyl) benzamido)-4-phenyl butyl amino) methyl)-5-isopropyl phenyl ammonia benzyl formate;n1-((2s, 3r)-4-(3-amino-5-isopropyl benzyl amino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(3-(dimethylamino)-5-isopropyl benzyl amino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(3-(benzyl oxygen base)-5-isopropyl benzyl amino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-3-hydroxyl-4-(3-sec.-propyl-5-(methanesulfonamido) benzylamino)-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-3-hydroxyl-4-(3-hydroxyl-5-isopropyl benzyl amino)-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;3-(((2r, 3s)-2-hydroxyl-3-(3-(methyl ((4-methylthiazol-2-yl) methyl) carbamyl) benzamido)-4-phenyl butyl amino) methyl)-5-isopropyl phenyl (methyl) ammonia benzyl formate;n1-((2s, 3r)-3-hydroxyl-4-(3-sec.-propyl-5-(methylamino) benzylamino)-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;3-(((2r, 3s)-2-hydroxyl-3-(3-(methyl ((4-methylthiazol-2-yl) methyl) carbamyl) benzamido)-4-phenyl butyl amino) methyl)-5-(n-methyl methanesulfonamido) methyl benzoate;n1-((2s, 3r)-3-hydroxyl-4-(3-hydroxybenzyl amino)-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(3-tertiary butyl benzylamino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-4-(3-cyclopropyl benzylamino)-3-hydroxyl-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-3-hydroxyl-4-(naphthalene-1-ylmethyl amino)-1-phenyl butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-3-hydroxyl-1-phenyl-4-(pyridin-3-yl methylamino) butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-3-hydroxyl-1-phenyl-4-(pyridin-4-yl methylamino) butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-3-hydroxyl-1-phenyl-4-(pyridine-2-ylmethyl amino) butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-3-hydroxyl-1-phenyl-4-(1-(pyridin-3-yl) ethylamino) butane-2-yl)-n3-methyl-n3-((4-methylthiazol-2-yl) methyl) isophthaloyl amine;n1-((2s, 3r)-3-hydroxyl-4...
베타-세크레타제 활성을 억제하는 이소프탈아미드 유도체본 발명은 신규한 베타-세크레타제 억제제 및 알츠하이머병의 치료 방법을 포함하는 그것의 사용 방법을 제공한다. N1-((2S,3R)-4-((5-(2-플루오로프로판-2-일)피리딘-3-일)메틸아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-((3-메톡시벤질)(메틸)아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3-(디메틸아미노)벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3-플루오로-5-(트리플루오로메틸)벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(2-플루오로-6-메톡시벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3-tert-부틸-2-히드록시벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(5-tert-부틸-2-히드록시벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3-아세틸벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3,5-디메톡시벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3,4-디메틸벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3,5-비스(트리플루오로메틸)벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; 메틸 3-(((2R,3S)-2-히드록시-3-(3-(메틸((4-메틸티아졸-2-일)메틸)카르바모일)벤즈아미도)-4-페닐부틸아미노)메틸)-5-메톡시벤조에이트; 3-(((2R,3S)-2-히드록시-3-(3-(메틸((4-메틸티아졸-2-일)메틸)카르바모일)벤즈아미도)-4-페닐부틸아미노)메틸)-5-메톡시벤조산; N1-((2S,3R)-3-히드록시-4-(3-요오도벤질아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3-클로로벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-(3-메톡시-5-(메틸카르바모일)벤질아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; 벤질 3-(((2R,3S)-2-히드록시-3-(3-(메틸((4-메틸티아졸-2-일)메틸)카르바모일)벤즈아미도)-4-페닐부틸아미노)메틸)-5-이소프로필페닐카르바메이트; N1-((2S,3R)-4-(3-아미노-5-이소프로필벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3-(디메틸아미노)-5-이소프로필벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3-(벤질옥시)-5-이소프로필벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-(3-이소프로필-5-(메틸술폰아미도)벤질아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-(3-히드록시-5-이소프로필벤질아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; 벤질 3-(((2R,3S)-2-히드록시-3-(3-(메틸((4-메틸티아졸-2-일)메틸)카르바모일)벤즈아미도)-4-페닐부틸아미노)메틸)-5-이소프로필페닐(메틸)카르바메이트; N1-((2S,3R)-3-히드록시-4-(3-이소프로필-5-(메틸아미노)벤질아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; 메틸 3-(((2R,3S)-2-히드록시-3-(3-(메틸((4-메틸티아졸-2-일)메틸)카르바모일)벤즈아미도)-4-페닐부틸아미노)메틸)-5-(N-메틸메틸술폰아미도)벤조에이트; N1-((2S,3R)-3-히드록시-4-(3-히드록시벤질아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3-tert-부틸벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-(3-시클로프로필벤질아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-(나프탈렌-1-일메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-1-페닐-4-(피리딘-3-일메틸아미노)부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-1-페닐-4-(피리딘-4-일메틸아미노)부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-1-페닐-4-(피리딘-2-일메틸아미노)부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-1-페닐-4-(1-(피리딘-3-일)에틸아미노)부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-((6-메틸피리딘-2-일)메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2R,3S)-3-히드록시-4-((5-이소프로필피리딘-3-일)메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-1-페닐-4-((6-(트리플루오로메틸)피리딘-3-일)메틸아미노)부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-1-페닐-4-((5-(트리플루오로메틸)피리딘-3-일)메틸아미노)부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-((4-이소프로필피리딘-2-일)메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-((6-이소프로필피리딘-2-일)메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-((2-이소프로필피리딘-4-일)메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; 메틸 6-(((2R,3S)-2-히드록시-3-(3-(메틸((4-메틸티아졸-2-일)메틸)카르바모일)벤즈아미도)-4-페닐부틸아미노)메틸)-2-메틸니코틴에이트; N1-((2S,3R)-3-히드록시-4-((5-(히드록시메틸)-6-메틸피리딘-2-일)메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-((5-(디메틸아미노)피리딘-3-일)메틸아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-((2-플루오로-5-이소프로필피리딘-3-일)메틸아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-((5-이소펜틸피리딘-3-일)메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-((6-메틸-5-(메틸티오메틸)피리딘-2-일)메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-((2,6-디이소프로필피리딘-4-일)메틸아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-((5-이소프로필피리딘-3-일)메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((R)-1-(4-메틸티아졸-2-일)에틸)이소프탈아미드; N1-((2S,3R)-4-((5-시클로프로필피리딘-3-일)메틸아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-1-페닐-4-((5-(프로프-1-엔-2-일)피리딘-3-일)메틸아미노)부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-((1-tert-부틸-5-메틸-1H-피라졸-4-일)메틸아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-((1-(2-메톡시에틸)-5-메틸-1H-피라졸-4-일)메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-3-히드록시-4-((4-메톡시피리미딘-2-일)메틸아미노)-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-((2S,3R)-4-((1H-인돌-7-일)메틸아미노)-3-히드록시-1-페닐부탄-2-일)-N3-메틸-N3-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-시클로프로필-N3-((2S,3R)-3-히드록시-1-페닐-4-(3-(트리플루오로메틸)벤질아미노)부탄-2-일)-N1-((4-메틸티아졸-2-일)메틸)이소프탈아미드; N1-시...