Bicyclic derivatives as modulators of ion channelsThe present invention relates to bicyclic compounds of formula (I); wherein Z,R,q,R,Q,R are as defined in claim 1 , useful as inhibitors of ion channels.The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.Formula i compound:or its pharmacy acceptable salt;wherein:ring z is the unsaturated or aromatic ring of 5-7 unit, has the heteroatoms that at least one is selected from o, s, n or nh;wherein z condenses alternatively in ring a; wherein a is the unsaturated or aromatic ring of optional substituted 5-7 unit; andwherein z or z with described fused rings a by the r that occurs for z time at the most zreplace; z is 0 to 4;each r zbe independently selected from r 1, r 2, r 3, r 4or r 5q is 0 to 2;q is valence link or c1-c6 straight or branched alkylidene chain, wherein two non-conterminous mu (methylene unit) at the most of q alternatively and independently by-co-,-cs-,-coco-,-conr 2,-conr 2nr 2-,-co 2-,-oco-,-nr 2co 2-,-o-,-nr 2conr 2-,-oconr 2-,-nr 2nr 2-,-nr 2nr 2co-,-nr 2co-,-s-,-so ,-so 2-,-nr 2-,-so 2nr 2, nr 2so 2-,-nr 2so 2nr 2-or inferior spiro cycloalkyl group partly replace; r qbe c 1-6aliphatic group, have 0-3 the heteroatomic 3-8 unit that independently is selected from o, s, n or nh is saturated, part is unsaturated or unsaturated monocyclic ring fully, the heteroatomic 8-12 unit that independently is selected from o, s, n or nh is saturated, part is unsaturated or complete unsaturated bicyclic ring is perhaps to have 0-5; r wherein qalternatively by at the most 4 independently be selected from r 1, r 2, r 3, r 4or r 5substituting group replace; r mand r nbe r independently 2r 1be the oxo base ,=nn (r 6) 2,=nn (r 7) 2,=nn (r 6r 7), r 6or (ch 2) n-y; n is 0,1 or 2;y is halogen, cn, no 2, cf 3, ocf 3, oh, sr 6, s (o) r 6, so 2r 6, nh 2, nhr 6, n (r 6) 2, nr 6r 8, cooh, coor 6or or 6perhaps two r on the adjacent ring atom 1constitute 1 together, 2-methylene-dioxy or ethylenedioxy; r 2be hydrogen or c1-c6 aliphatic group, wherein each r 2alternatively by at the most 2 independently be selected from r 1, r 4or r 5substituting group replace; r 3be c3-c8 cyclic aliphatic base, c6-c10 aryl, c3-c8 heterocyclic radical or c5-c10 heteroaryl ring, alternatively by at the most 3 independently be selected from r 1, r 2, r 4or r 5substituting group replace; r 4be or 5, or 6, oc (o) r 6, oc (o) r 5, oc (o) or 6, oc (o) or 5, oc (o) n (r 6) 2, oc (o) n (r 5) 2, oc (o) n (r 6r 5), op (o) (or 6) 2, op (o) (or 5) 2, op (o) (or 6) (or 5), sr 6, sr 5, s (o) r 6, s (o) r 5, so 2r 6, so 2r 5, so 2n (r 6) 2, so 2n (r 5) 2, so 2nr 5r 6, so 3r 6, so 3r 5, c (o) r 5, c (o) or 5, c (o) r 6, c (o) or 6, c (o) n (r 6) 2, c (o) n (r 5) 2, c (o) n (r 5r 6), c (o) n (or 6) r 6, c (o) n (or 5) r 6, c (o) n (or 6) r 5, c (o) n (or 5) r 5, c (nor 6) r 6, c (nor 6) r 5, c (nor 5) r 6, c (nor 5) r 5, n (r 6) 2, n (r 5) 2, n (r 5r 6), nr 5c (o) r 5, nr 6c (o) r 6, nr 6c (o) r 5, nr 6c (o) or 6, nr 5c (o) or 6, nr 6c (o) or 5, nr 5c (o) or 5, nr 6c (o) n (r 6) 2, nr 6c (o) nr 5r 6, nr 6c (o) n (r 5) 2, nr 5c (o) n (r 6) 2, nr 5c (o) nr 5r 6, nr 5c (o) n (r 5) 2, nr 6so 2r 6, nr 6so 2r 5, nr 5so 2r 5, nr 6so 2n (r 6) 2, nr 6so 2nr 5r 6, nr 6so 2n (r 5) 2, nr 5so 2nr 5r 6, nr 5so 2n (r 5) 2, n (or 6) r 6, n (or 6) r 5, n (or 5) r 5, n (or 5) r 6, p (o) (or 6) n (r 6) 2, p (o) (or 6) n (r 5r 6), p (o) (or 6) n (r 5) 2, p (o) (or 5) n (r 5r 6), p (o) (or 5) n (r 6) 2, p (o) (or 5) n (r 5) 2, p (o) (or 6) 2, p (o) (or 5) 2or p (o) (or 6) (or 5); r 5be c3-c8 cyclic aliphatic base, c6-c10 aryl, c3-c8 heterocyclic radical or c5-c10 heteroaryl ring, alternatively by 3 r at the most 1substituting group replaces; r 6be h or c1-c6 aliphatic group, wherein r 6alternatively by r 7substituting group replaces; r 7be c3-c8 cyclic aliphatic base, c6-c10 aryl, c3-c8 heterocyclic radical or c5-c10 heteroaryl ring, and each r 7alternatively by at the most 2 independently be selected from h, c1-c6 aliphatic group or (ch 2) mthe substituting group of-z ' replaces, and wherein m is 0-2; z ' is selected from halogen, cn, no 2, c (halogen) 3, ch (halogen) 2, ch 2(halogen) ,-oc (halogen) 3,-och (halogen) 2,-och 2(halogen), oh, s-(c1-c6) aliphatic group, s (o)-(c1-c6) aliphatic group, so 2-(c1-c6) aliphatic group, nh 2, nh-(c1-c6) aliphatic group, n ((c1-c6) aliphatic group) 2, n ((c1-c6) aliphatic group) r 8, cooh, c (o) o ((c1-c6) aliphatic group) or o-(c1-c6) aliphatic group; r 8be ethanoyl, c6-c10 aryl sulfonyl or c1-c6 alkyl sulphonyl; and its condition is that described compound is not n-[4-cyano group-5-(methylthio group)-1h-pyrazole-3-yl]-1,2-dihydro-1-methyl-2-oxo-4-(trifluoromethyl)-6-quinoline sulphonamide.
이온 채널 조절인자로서의 바이사이클릭 유도체 본 발명은 이온 채널의 억제제로서 유용한 화학식 I의 바이사이클릭 화합물에 관한 것이다. 화학식 I  상기 화학식 I에서, Z, RN, q, RM, Q 및 RQ는 제1항에 정의된 바와 같다. 본 발명은 또한 약제학적으로 허용되는 조성물 및 다양한 장애의 치료에서 당해 조성물을 사용하는 방법을 제공한다. 화학식 I의 화합물 또는 약제학적으로 허용되는 이의 염. 화학식 I [이미지] 상기 화학식 I에서, 환 Z는 O, S, N 및 NH로부터 선택된 하나 이상의 환 헤테로원자를 갖는 5 내지 7원의 불포화 또는 방향족 환이고; 여기서, Z는 임의로 환 A에 융합되고; 이때, A는 임의로 치환된 5 내지 7원의 불포화 또는 방향족 환이고; 여기서, Z 또는 융합된 환 A와 함께 Z는 RZ로 z회 이하로 치환되고; z는 0 내지 4이고; RZ는 각각 독립적으로 R1, R2, R3, R4 및 R5로부터 선택되고; q는 0 내지 2이고; Q는 결합 또는 C1-C6 직쇄 또는 측쇄 알킬리덴 쇄이고, 여기서, Q의 2개 이하의 인접하지 않은 메틸렌 단위는 임의로 및 독립적으로 -CO-, - CS-, -COCO-, -CONR2-, -CONR2NR2-, -CO2-, -OCO-, -NR2CO2-, -O-, -NR2CONR2-, -OCONR2-, -NR2NR2-, -NR2NR2CO-, -NR2CO-, -S-, -SO, -SO2-, -NR2-, -SO2NR2-, NR2SO2-, -NR2SO2NR2-, 또는 스피로사이클로알킬렌 잔기에 의해 치환되고; RQ는 C1-6 지방족 그룹, O, S, N 및 NH로부터 독립적으로 선택된 0 내지 3개의 헤테로원자를 갖는 3 내지 8-원의 포화되거나, 부분 불포화되거나, 완전히 불포화된 모노사이클릭 환, 또는 O, S, N 및 NH로부터 독립적으로 선택된 0 내지 5개의 헤테로원자를 갖는 8 내지 12원의 포화되거나, 부분 불포화되거나, 완전히 불포화된 바이사이클릭 환 시스템이고; 여기서, RQ는 R1, R2, R3, R4 및 R5로부터 독립적으로 선택된 4개 이하의 치환체로 임의로 치환되고; RM 및 RN은 독립적으로 R2이고; R1은 옥소, =NN(R6)2, =NN(R7)2, =NN(R6R7), R6, 또는 (CH2)n-Y이고; n은 0, 1, 또는 2이고; Y는 할로, CN, NO2, CF3, OCF3, OH, SR6, S(O)R6, SO2R6, NH2, NHR6, N(R6)2, NR6R8, COOH, COOR6, 또는 OR6이고; 또는 인접한 환 원자에서 2개의 R1은 1,2-메틸렌디옥시 또는 1,2-에틸렌디옥시를 형성하고; R2는 수소 또는 C1-C6 지방족이고, 여기서, R2는 각각 R1, R4 및 R5로부터 독립적으로 선택된 2개 이하의 치환체로 임의로 치환되고; R3은 R1, R2, R4 및 R5로부터 독립적으로 선택된 3개 이하의 치환체로 임의로 치환된, C3-C8 지환족, C6-C10 아릴, C3-C8 헤테로사이클릭, 또는 C5-C10 헤테로아릴 환이고; R4는 OR5, OR6, OC(O)R6, OC(O)R5, OC(O)OR6, OC(O)OR5, OC(O)N(R6)2, OC(O)N(R5)2, OC(O)N(R6R5), OP(O)(OR6)2, OP(O)(OR5)2, OP(O)(OR6)(OR5), SR6, SR5, S(O)R6, S(O)R5, SO2R6, SO2R5, SO2N(R6)2, SO2N(R5)2, SO2NR5R6, SO3R6, SO3R5, C(O)R5, C(O)OR5, C(O)R6, C(O)OR6, C(O)N(R6)2, C(O)N(R5)2, C(O)N(R5R6), C(O)N(OR6)R6, C(O)N(OR5)R6, C(O)N(OR6)R5, C(O)N(OR5)R5, C(NOR6)R6, C(NOR6)R5, C(NOR5)R6, C(NOR5)R5, N(R6)2, N(R5)2, N(R5R6), NR5C(O)R5, NR6C(O)R6, NR6C(O)R5, NR6C(O)OR6, NR5C(O)OR6, NR6C(O)OR5, NR5C(O)OR5, NR6C(O)N(R6)2, NR6C(O)NR5R6, NR6C(O)N(R5)2, NR5C(O)N(R6)2, NR5C(O)NR5R6, NR5C(O)N(R5)2, NR6SO2R6, NR6SO2R5, NR5SO2R5, NR6SO2N(R6)2, NR6SO2NR5R6, NR6SO2N(R5)2, NR5SO2NR5R6, NR5SO2N(R5)2, N(OR6)R6, N(OR6)R5, N(OR5)R5, N(OR5)R6, P(O)(OR6)N(R6)2, P(O)(OR6)N(R5R6), P(O)(OR6)N(R5)2, P(O)(OR5)N(R5R6), P(O)(OR5)N(R6)2, P(O)(OR5)N(R5)2, P(O)(OR6)2, P(O)(OR5)2, 또는 P(O)(OR6)(OR5)이고; R5는 3개 이하의 R1 치환체에 의해 임의로 치환된, C3-C8 지환족, C6-C10 아릴, C3-C8 헤테로사이클릭, 또는 C5-C10 헤테로아릴 환이고; R6은 H 또는 C1-C6 지방족이고, 여기서, R6은 R7 치환체로 임의로 치환되고; R7은 C3-C8 지환족, C6-C10 아릴, C3-C8 헤테로사이클릭, 또는 C5-C10 헤테로아릴 환이고, R7은 각각 임의로 H, C1-C6 지방족 및 (CH2)m-Z'로부터 독립적으로 선택된 2개 이하의 치환체로 치환되고, 여기서, m은 0 내지 2이고; Z'는 할로, CN, NO2, C(할로)3, CH(할로)2, CH2(할로), -OC(할로)3, - OCH(할로)2, -OCH2(할로), OH, S-(C1-C6) 지방족, S(O)-(C1-C6) 지방족, SO2-(C1-C6)지방족, NH2, NH-(C1-C6)지방족, N((C1-C6)지방족)2, N((C1-C6)지방족)R8, COOH, C(O)O(-(C1-C6)지방족) 및 O-(C1-C6)지방족으로부터 선택되고; R8은 아세틸, C6-C10 아릴 설포닐 또는 C1-C6 알킬 설포닐이고; 단, 당해 화합물은 N-[4-시아노-5-(메틸티오)-1H-피라졸-3-일]-1,2-디하이드로-1-메틸-2-옥소-4-(트리플루오로메틸)-6-퀴놀린설폰아미드가 아니다.