Aminochromane, aminothiochromane and amino-1,2,3,4-tetrahydroquinoline derivatives, pharmaceutical compositions containing them, and their use in therapyThe present invention relates to aminochromane, aminothiochromane and amino-1,2,3,4- tetrahydroquinoline derivatives of the formula (I) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such aminochromane, aminothio-chromane and amino-1,2,3,4-tetrahydroquinoline derivatives, and the use of such aminochromane, aminothiochromane and amino-1,2,3,4-tetrahydroquinoline derivatives for therapeutic purposes. The aminochromane, aminothiochromane and amino-1,2,3,4-tetrahydroquinoline derivatives are GlyT1 inhibitors.The compound of formula (i), or its salt physiologically toleratedwhereina is 5 or 6 rings；r1for hydrogen, c1-c6alkyl, c3-c12cycloalkyl-c1-c4alkyl, halo c1-c6alkyl, three-(c1-c4alkyl)-monosilane base-c1-c4alkyl, hydroxyl-c1-c4alkyl, c1-c6alkoxy-c1-c4alkyl, amino-c1-c4alkyl, c1-c6alkyl amino- c1-c4alkyl, two-c1-c6alkyl amino-c1-c4alkyl, c1-c6alkyl-carbonyl-amino-c1-c4alkyl, c1-c6alkoxy carbonyl amino-c1-c4alkyl, c1-c6alkyl amino-carbonyl-amino-c1-c4alkyl, two-c1-c6alkyl amino-carbonyl-amino-c1-c4alkane base, c1-c6alkyl sulfonyl-amino-c1-c4alkyl, (optionally substituted c6-c12aryl-c1-c6alkyl) amino-c1-c4alkyl, optionally substituted c6-c12aryl-c1-c4alkyl, optionally substituted m3-m12heterocyclic radical-c1-c4alkyl, c3-c12cycloalkyl, c1-c6 alkyl-carbonyl, c1-c6alkoxy carbonyl, halo c1-c6alkoxy carbonyl, c6-c12aryloxycarbonyl, amino carbonyl, c1-c6alkyl amino carbonyl, (halo c1-c4alkyl) amino carbonyl, c6-c12aromatic yl aminocarbonyl, c2-c6thiazolinyl, c2-c6alkynyl, optionally substituted c6-c12aryl, hydroxyl, c1-c6alkoxyl, halo c1-c6alkoxyl, c1-c6hydroxy alkoxy base, c1-c6alkoxy-c1-c4alkane epoxide, amino-c1-c4alkoxyl, c1-c6alkyl amino-c1-c4alkoxyl, two-c1-c6alkyl amino-c1-c4alkoxyl, c1- c6alkyl-carbonyl-amino-c1-c4alkoxyl, c6-c12aryl-amino-carbonyl-c1-c4alkoxyl, c1-c6alkoxycarbonyl amino-c1- c4alkoxyl, c6-c12aryl-c1-c4alkoxyl, c1-c6alkyl sulfonyl-amino-c1-c4alkoxyl, (halo c1-c6-alkyl) sulfuryl amino-c1-c4alkoxyl, c6-c12arlysulfonylamino-c1-c4alkoxyl, (c6-c12aryl-c1-c6alkyl) sulphur acyl amino-c1-c4alkoxyl, m3-m12heterocyclyl sulfonyl amino-c1-c4alkoxyl, m3-m12heterocyclic radical-c1-c4alkoxyl, c6-c12aryloxy group, m3-m12heterocyclic radical epoxide, c1-c6alkyl sulfenyl, halo c1-c6alkyl sulfenyl, c1-c6alkyl amino, (halo c1-c6alkyl) amino, two-c1-c6alkyl amino, two-(halo c1-c6alkyl) amino, c1-c6alkyl-carbonyl-amino, (halo c1-c6alkyl) carbonylamino, c6-c12aryl-amino-carbonyl, c1-c6alkyl sulfonyl-amino, (halo c1-c6alkyl) sulfonyl amino, c6-c12arlysulfonylamino or optionally substituted m3-m12heterocyclic radical；w is-nr7-or key；a1for optionally substituted c1-c4alkylidene or key；q is-s (o)2-or-c (o)-；y is-nr8-or key；n1 is 0,1,2 or 3,n2 is 0,1,2 or 3,x1for > n-or > ch-；r6for hydrogen, halogen, c1-c4alkyl, halo c1-c4alkyl ,-cn, oh, c1-c6alkoxyl or halo c1-c6alkoxyl, or two individual group r6carbonyl is formed together with its carbon atom connected；r2for hydrogen, halogen, c1-c6alkyl, halo c1-c4alkyl ,-cn, c2-c6thiazolinyl, c2-c6alkynyl, optionally substituted c6-c12 aryl, hydroxyl, c1-c6alkoxyl, halo c1-c6alkoxyl, c1-c6alkoxy carbonyl, c2-c6alkenyloxy group, c6-c12aryl-c1- c4alkoxyl, c1-c6alkyl-carbonyl epoxide, c1-c6alkyl sulfenyl, c1-c6alkyl sulphinyl, c1-c6alkyl sulphonyl, amino sulfonyl, amino, c1-c6alkyl amino, c2-c6alkenyl amino, nitro or optionally substituted m3-m12heterocyclic radical, or two groups r2annular atoms together with its a being bonded forms 5 or 6 rings；a2for-o-,-s-or-nr9-；r3for hydrogen, halogen, c1-c6alkyl or c1-c6alkoxyl, or two group r3formed together with its carbon atom connected carbonyl；y1for key or optionally substituted c1-c4alkylidene；r4afor hydrogen, c1-c6alkyl, c3-c12cycloalkyl-c1-c4alkyl, halo c1-c4alkyl, hydroxyl-c1-c4alkyl, c1-c6alkane epoxide-c1-c4alkyl, amino-c1-c4alkyl ,-ch2cn、c6-c12aryl-c1-c4alkyl, optionally substituted c3-c12cycloalkanes base ,-cho, c1-c4alkyl-carbonyl, (halo c1-c4alkyl) carbonyl, c6-c12aryl carbonyl, c1-c4alkoxy carbonyl, c6-c12virtue epoxide carbonyl, c1-c6alkyl amino-carbonyl, c2-c6thiazolinyl ,-c (=nh) nh2、-c(=nh)nhcn、c1-c6alkyl sulphonyl, c6- c12aryl sulfonyl, amino ,-no or optionally substituted m3-m12heterocyclic radical；orr4afor with y1in the optionally substituted c of carbon atom bonding1-c4alkylidene；r4bfor hydrogen, c1-c6alkyl, halo c1-c4alkyl, hydroxyl-c1-c4alkyl, c1-c6alkoxy-c1-c4alkyl, amino-c1- c4alkyl ,-ch2cn、-cho、c1-c4alkyl-carbonyl, (halo c1-c4alkyl) carbonyl, c6-c12aryl carbonyl, c1-c4alkoxyl carbonyl base, c6-c12aryloxycarbonyl, c1-c6alkyl amino-carbonyl, c2-c6thiazolinyl ,-c (=nh) nh2、-c(=nh)nhcn、c1-c6alkyl sulfonyl, c6-c12aryl sulfonyl, amino ,-no or m3-m12heterocyclic radical；orr4a、r4bit is optionally substituted c together2-c6alkylidene, wherein c2-c6one-ch of alkylidene2-can be by oxygen atom or-nr10substitute；x2for-o-,-nr11a-、-s-、>cr12ar12bor key；x3for-o-,-nr11b-、-s-、>cr13ar13bor key；r5for optionally substituted c6-c12aryl, optionally substituted c3-c12cycloalkyl or optionally substituted m3-m12heterocyclic radical；r7for hydrogen or c1-c6alkyl；r8for hydrogen, c1-c6alkyl, c3-c12cycloalkyl, amino-c1-c6alkyl, optionally substituted c6-c12aryl-c1-c4alkyl or m3-m12heterocyclic radical；orr8、r1it is c together1-c4alkylidene；r9for hydrogen, c1-c6alkyl, c3-c12cycloalkyl-c1-c4alkyl, halo c1-c4alkyl, hydroxyl-c1-c4alkyl, c1-c6alcoxyl base-c1-c4alkyl, amino-c1-c4alkyl, ch2cn、c6-c12aryl-c1-c4alkyl, c3-c12cycloalkyl ,-cho, c1-c4alkyl carbonyl, (halo c1-c4alkyl) carbonyl, c6-c12aryl carbonyl, c1-c4alkoxy carbonyl, c6-c12aryloxycarbonyl, ...
아미노크로만, 아미노티오크로만 및 아미노-1,2,3,4-테트라하이드로퀴놀린 유도체, 이들을 포함하는 약제학적 조성물, 및 치료에서 이들의 용도본 발명은 화학식 I의 아미노크로만, 아미노티오크로만 및 아미노-1,2,3,4-테트라하이드로퀴놀린 유도체 또는 생리학적으로 허용되는 이의 염에 관한 것이다. 화학식 I 본 발명은 이러한 아미노크로만, 아미노티오크로만 및 아미노-1,2,3,4-테트라하이드로퀴놀린 유도체를 포함하는 약제학적 조성물, 및 아미노크로만, 아미노티오크로만 및 아미노-1,2,3,4-테트라하이드로퀴놀린 유도체의 치료학적 목적을 위한 용도에 관한 것이다. 아미노크로만, 아미노티오크로만 및 아미노-1,2,3,4-테트라하이드로퀴놀린 유도체는 GlyT1 억제제이다.화학식 I의 화합물 또는 생리학적으로 허용되는 이의 염.화학식 I[이미지]상기 화학식 I에서, A는 5- 또는 6-원 환이고; R1은 수소, C1-C6-알킬, C3-C12-사이클로알킬-C1-C4-알킬, 할로겐화된 C1-C6-알킬, 트리-(C1-C4-알킬)-실릴-C1-C4-알킬, 하이드록시-C1-C4-알킬, C1-C6-알콕시-C1-C4-알킬, 아미노-C1-C4-알킬, C1-C6-알킬아미노-C1-C4-알킬, 디-C1-C6-알킬아미노-C1-C4-알킬, C1-C6-알킬카보닐아미노-C1-C4-알킬, C1-C6-알킬옥시카보닐아미노-C1-C4-알킬, C1-C6-알킬아미노카보닐아미노-C1-C4-알킬, 디-C1-C6-알킬아미노카보닐아미노-C1-C4-알킬, C1-C6-알킬설포닐아미노-C1-C4-알킬, (임의로 치환된 C6-C12-아릴-C1-C6-알킬)아미노-C1-C4-알킬, 임의로 치환된 C6-C12-아릴-C1-C4-알킬, 임의로 치환된 M3-M12-헤테로사이클릴-C1-C4-알킬, C3-C12-사이클로알킬, C1-C6-알킬카보닐, C1-C6-알콕시카보닐, 할로겐화된 C1-C6-알콕시카보닐, C6-C12-아릴옥시카보닐, 아미노카보닐, C1-C6-알킬아미노카보닐, (할로겐화된 C1-C4-알킬)아미노카보닐, C6-C12-아릴아미노카보닐, C2-C6-알케닐, C2-C6-알키닐, 임의로 치환된 C6-C12-아릴, 하이드록시, C1-C6-알콕시, 할로겐화된 C1-C6-알콕시, C1-C6-하이드록시알콕시, C1-C6-알콕시-C1-C4-알콕시, 아미노-C1-C4-알콕시, C1-C6-알킬아미노-C1-C4-알콕시, 디-C1-C6-알킬아미노-C1-C4-알콕시, C1-C6-알킬카보닐아미노-C1-C4-알콕시, C6-C12-아릴카보닐아미노-C1-C4-알콕시, C1-C6-알콕시카보닐아미노-C1-C4-알콕시, C6-C12-아릴-C1-C4-알콕시, C1-C6-알킬설포닐아미노-C1-C4-알콕시, (할로겐화된 C1-C6-알킬)설포닐아미노-C1-C4-알콕시, C6-C12-아릴설포닐아미노-C1-C4-알콕시, (C6-C12-아릴-C1-C6-알킬)설포닐아미노-C1-C4-알콕시, M3-M12-헤테로사이클릴설포닐아미노-C1-C4-알콕시, M3-M12-헤테로사이클릴-C1-C4-알콕시, C6-C12-아릴옥시, M3-M12-헤테로사이클릴옥시, C1-C6-알킬티오, 할로겐화된 C1-C6-알킬티오, C1-C6-알킬아미노, (할로겐화된 C1-C6-알킬)아미노, 디-C1-C6-알킬아미노, 디-(할로겐화된 C1-C6-알킬)아미노, C1-C6-알킬카보닐아미노, (할로겐화된 C1-C6-알킬)카보닐아미노, C6-C12-아릴카보닐아미노, C1-C6-알킬설포닐아미노, (할로겐화된 C1-C6-알킬)설포닐아미노, C6-C12-아릴설포닐아미노 또는 임의로 치환된 M3-M12-헤테로사이클릴이고; W는 -NR7- 또는 결합이고;A1은 임의로 치환된 C1-C4-알킬렌 또는 결합이고;Q는 -S(O)2- 또는 -C(O)-이고;Y는 -NR8- 또는 결합이고;n1은 0, 1, 2, 또는 3이고;n2는 0, 1, 2, 또는 3이고;X1은 >N- 또는 >CH-이고;R6은 수소, 할로겐, C1-C4-알킬, 할로겐화된 C1-C4-알킬, -CN, OH, C1-C6-알콕시 또는 할로겐화된 C1-C6-알콕시이거나, 2개의 라디칼 R6은, 이들이 부착된 탄소 원자와 함께, 카보닐 그룹을 형성하고; R2는 수소, 할로겐, C1-C6-알킬, 할로겐화된 C1-C4-알킬, -CN, C2-C6-알케닐, C2-C6-알키닐, 임의로 치환된 C6-C12-아릴, 하이드록시, C1-C6-알콕시, 할로겐화된 C1-C6-알콕시, C1-C6-알콕시카보닐, C2-C6-알케닐옥시, C6-C12-아릴-C1-C4-알콕시, C1-C6-알킬카보닐옥시, C1-C6-알킬티오, C1-C6-알킬설피닐, C1-C6-알킬설포닐, 아미노설포닐, 아미노, C1-C6-알킬아미노, C2-C6-알케닐아미노, 니트로 또는 임의로 치환된 M3-M12-헤테로사이클릴이거나, 2개의 라디칼 R2는, 이들이 결합된 A의 환 원자와 함께, 5- 또는 6-원 환을 형성하고;A2는 -O-, -S- 또는 -NR9-이고;R3은 수소, 할로겐, C1-C6-알킬 또는 C1-C6-알콕시이거나, 2개의 라디칼 R3은, 이들이 부착된 탄소 원자와 함께, 카보닐 그룹을 형성하고;Y1은 결합 또는 임의로 치환된 C1-C4-알킬렌이고;R4a는 수소, C1-C6-알킬, C3-C12-사이클로알킬-C1-C4-알킬, 할로겐화된 C1-C4-알킬, 하이드록시-C1-C4-알킬, C1-C6-알콕시-C1-C4-알킬, 아미노-C1-C4-알킬, -CH2CN, C6-C12-아릴-C1-C4-알킬, 임의로 치환된 C3-C12-사이클로알킬, -CHO, C1-C4-알킬카보닐, (할로겐화된 C1-C4-알킬)카보닐, C6-C12-아릴카보닐, C1-C4-알콕시카보닐, C6-C12-아릴옥시카보닐, C1-C6-알킬아미노카보닐, C2-C6-알케닐, -C(=NH)NH2, -C(=NH)NHCN, C1-C6-알킬설포닐, C6-C12-아릴설포닐, 아미노, -NO 또는 임의로 치환된 M3-M12-헤테로사이클릴이거나;R4a는 Y1에서 탄소 원자에 결합된 임의로 치환된 C1-C4-알킬렌이고;R4b는 수소, C1-C6-알킬, 할로겐화된 C1-C4-알킬, 하이드록시-C1-C4-알킬, C1-C6-알콕시-C1-C4-알킬, 아미노-C1-C4-알킬, -CH2CN, -CHO, C1-C4-알킬카보닐, (할로겐화된 C1-C4-알킬)카보닐, C6-C12-아릴카보닐, C1-C4-알콕시카보닐, C6-C12-아릴옥시카보닐, C1-C6-알킬아미노카보닐, C2-C6-알케닐, -C(=NH)NH2, -C(=NH)NHCN, C1-C6-알킬설포닐, C6-C12-아릴설포닐, 아미노, -NO 또는 M3-M12-헤테로사이클릴이거나; R4a, R4b는 함께 임의로 치환된 C2-C6-알킬렌이고, 여기서, C2-C6-알킬렌의 하나의 -CH2-는 산소 원자 또는 -NR10으로 대체될 수 있고;X2는 -O-, -NR11a-, -S-, >CR12aR12b 또는 결합이고;X3은 -O-, -NR11b-, -S-, >CR13aR13b 또는 결합이고;R5는 임의로 치환된 C6-C12-아릴, 임의로 치환된 C3-C12-사이클로알킬 또는 임의로 치환된 M3-M12-헤테로사이클릴이고; R7은 수소 또는 C1-C6-알킬이고;R8은 수소, C1-C6-알킬, C3-C12-사이클로알킬, 아미노-C1-C6-알킬, 임의로 치환된 C6-C12-아릴-C1-C4-알킬 또는 M3-M12-헤테로사이클릴이거나;R8, R1은 함께 C1-C4-알킬렌이고;R9는 수소, C1-C6-알킬, C3-C12-사이클로알킬-C1-C4-알킬, 할로겐화된 C1-C4-알킬, 하이드록시-C1-C4-알킬, C1-C6-알콕시-C1-C4-알킬, 아미노-C1-C4-알킬, CH2CN, C6-C12-아릴-C1-C4-알킬, C3-C12-사이클로알킬, -CHO, C1-C4-알킬카보닐, (할로겐화된 C1-C4-알킬)카보닐, C6-C12-아릴카보닐, C1-C4-알콕시카보닐, C6-C12-아릴옥시카보닐, C1-C6-알킬아미노카보닐, C2-C6-알케닐, -C(=NH)NH2, -C(=NH)NHCN, C1-C6-알킬설포닐, C6-C12-아릴설포닐, 아미노, -NO 또는 M3-M12-헤테로사이클릴이고;R10은 수소 또는 C1-C6-알킬이고;R11a는 수소 또는 C1-C6-알킬이고;R11b는 수소 또는 C1-C6-알킬이고;R12a는 수소, 임의로 치환된 C1-C6-알킬, C1-C6-알킬아미노-C1-C4-알킬, 디-C1-C6-알킬아미노-C1-C4-알킬, M3-M12-헤테로사이클릴-C1-C6-알킬, 임의로 치환된 C6-C12-아릴 또는 하이드록시이고;R12b는 수소 또는 C1-C6-알킬이거나, R12a, R12b는, 이들이 부착된 탄소 원자와 함께, 카보닐을 형성하거나, 임의로 치환된 C2-C4-알킬렌이고, 여기서, C2-C4-알킬렌의 하나의 -CH2-는 산소 원자 또는 -NR14-로 대체될 수 있고; R13a는 수소, 임의로 치환된 C1-C6-알킬, C1-C6-알킬아미노-C1-C4-알킬, 디-C1-C6-알킬아미노-C1-C4-알킬, M3-M12-헤테로사이클릴-C1-C6-알킬, 임의로 치환된 C6-C12-아릴 또는 하이드록시이고;R13b는 수소 또는 C1-C6-알킬이거나, R13a, R13b는, 이들이 부착된 탄소 원자와 함께, 카보닐을 형성하거나, 임의로 치환된 C2-C4-알킬렌이고, 여기서, C2-C4-알킬렌의 하나의 -CH2-는 산소 원자 또는 -NR15-로 대체될 수 있고; R14는 수소 또는 C1-C6-알킬이고; R15는 수소 또는 C1-C6-알킬이다.