Biphenyl derivatives as modulators of voltage gated ion channelsBiphenyl derivatives useful as ion channel antagonists are disclosed herein. The compositions thereof are useful for treating or relieving pain-related conditions.Formula i compound:or its pharmacy acceptable salt;wherein:ring z is the unsaturated or aromatic ring of 5-7 unit with at least one ring hetero atom that is selected from o, s, n and nh, and wherein z is optionally 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 4and r 5so 2group is connected in no. 1 or no. 2 carbon; nr m-c (o)-q-r qbe connected in 3 ' number or 4 ' number carbon; the benzyl ring that wherein contains 3 ' number carbon optionally by at the most 4 be selected from halogeno-group, cn, no 2, cf 3, ocf 3, or 6, sr 6, s (o) r 2, so 2r 2, nh 2, n (r 2) 2, coor 2replace with the substituting group of c1-c6 straight or branched alkylidene chain, two non-conterminous mu (methylene unit) at the most of wherein said alkylidene group optionally 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-or-nr 2so 2nr 2-replace; q is valence link or c1-c6 straight or branched alkylidene chain, wherein two non-conterminous mu (methylene unit) at the most of q optionally 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, the heteroatomic 3-8 unit that independently is selected from o, s, n and nh is saturated, part is unsaturated or complete undersaturated monocycle to have 0-3, perhaps has 0-5 the heteroatomic 8-12 unit that independently is selected from o, s, n and nh is saturated, part is unsaturated or complete undersaturated bicyclic ring system; r wherein qoptionally by at the most 4 be selected from r 1, r 2, r 3, r 4and r 5substituting group replace; each r nand r mbe 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 halogeno-group, 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 2optionally by at the most 2 independently be selected from r 1, r 4and r 5substituting group replace; r 3be c3-c8 cyclic aliphatic base, c6-c10 aryl, c3-c8 heterocyclic radical or c5-c10 heteroaryl ring, optionally by at the most 3 independently be selected from r 1, r 2, r 4and 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, optionally by 3 r at the most 1substituting group replaces; r 6be h or c1-c6 aliphatic group, wherein r 6optionally by r 7substituting group replaces; r 7be c3-c8 cyclic aliphatic base, c6-c10 aryl, c3-c8 heterocyclic radical or c5-c10 heteroaryl ring, each r 7optionally 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 halogeno-group, cn, no 2, c (halogeno-group) 3, ch (halogeno-group) 2, ch 2(halogeno-group) ,-oc (halogeno-group) 3,-och (halogeno-group) 2,-och 2(halogeno-group), 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) and o-(c1-c6) aliphatic group; and r 8be ethanoyl, c6-c10 aryl sulfonyl or c1-c6 alkyl sulphonyl; if its condition is r mand r nall be hydrogen, and q is valence link, r then qit or not methyl.
전압 개폐 이온 채널 조절인자로서의 바이페닐 유도체 본 발명은 이온 채널 길항제로서 유용한 바이페닐 유도체를 기술한다. 이의 조성물은 통증 관련 상태를 치료하거나 경감시키는데 유용하다. 화학식 I의 화합물 또는 약제학적으로 허용되는 이의 염. 화학식 I [이미지] 위의 화학식 I에서, 환 Z는 O, S, N 및 NH로부터 선택된 하나 이상의 환 헤테로원자를 갖는 5 내지 7원의 불포화 또는 방향족 환이고, 여기서 Z는 Rz로 z회 이하로 임의로 치환되고, z는 0 내지 4이고, 각각의 Rz는 독립적으로 R1, R2, R3, R4 및 R5로부터 선택되고, SO2 그룹은 1번 또는 2번 탄소에 결합되고, NRM-C(O)-Q-RQ는 3'번 또는 4'번 탄소에 결합되고, 3'번 탄소를 함유하는 페닐 환은 할로, CN, NO2, CF3, OCF3, OR6, SR6, S(O)R2, SO2R2, NH2, N(R2)2, COOR2 및 C1-C6 직쇄 또는 측쇄 알킬리덴 쇄로부터 선택된 4개 이하의 치환체로 임의로 치환되고, 상기 알킬리덴의 2개 이하의 비인접 메틸렌 단위는 독립적으로 -CO-, -CS-, -COCO-, -CONR2-, -CONR2NR2-, -CO2-, -OCO-, -NR2CO2-, -0-, -NR2CONR2-, -OCONR2-, -NR2NR2-, -NR2NR2CO-, -NR2CO-, -S-, -SO-, -SO2-, -NR2-, -SO2NR2-, NR2SO2- 또는 -NR2SO2NR2-로 임의로 교체되고, Q는 결합이거나, C1-C6 직쇄 또는 측쇄 알킬리덴 쇄이고, Q의 2개 이하의 비인접 메틸렌 단위는 독립적으로 -CO-, -CS-, -COCO-, -CONR2-, -CONR2NR2-, -CO2-, -OCO-, -NR2CO2-, -0-, -NR2CONR2-, -OCONR2-, -NR2NR2-, -NR2NR2CO-, -NR2CO-, -S-, -SO-, -SO2-, -NR2-, -SO2NR2-, NR2SO2-, -NR2SO2NR2- 또는 스피로사이클로알킬렌 잔기로 임의로 교체되고, RQ는 O, S, N 및 NH로부터 독립적으로 선택된 0 내지 3개의 헤테로원자를 갖는 C1-6 지방족 그룹, 3 내지 8원의 포화, 부분 불포화 또는 완전 불포화 모노사이클릭 환, 또는 O, S, N 및 NH로부터 독립적으로 선택된 0 내지 5개의 헤테로원자를 갖는 8 내지 12원의 포화, 부분 불포화 또는 완전 불포화 바이사이클릭 환 시스템이고, 여기서, RQ는 R1, R2, R3, R4 및 R5로부터 선택된 4개 이하의 치환체로 임의로 치환되고, 각각의 RN 및 RM은 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 OR6이거나, 인접 환 원자 상의 2개의 R1이 함께 1,2-메틸렌디옥시 또는 1,2-에틸렌디옥시를 형성하고, R2는 수소 또는 C1-C6 지방족이고, 여기서 각각의 R2는 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 사이클로지방족, 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 치환체로 임의로 치환된 C3-C8 사이클로지방족, 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 사이클로지방족, C6-C10 아릴, C3-C8 헤테로사이클릭 또는 C5-C10 헤테로아릴 환이고, 각각의 R7은 H, C1-C6 지방족 및 (CH2)m-Z'로부터 독립적으로 선택된 2개 이하의 치환체로 임의로 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)지방족로부터 선택되고, R8은 아세틸, C6-C10 아릴 설포닐 또는 C1-C6 알킬 설포닐이고, 단, RM 및 RN이 둘 다 수소이고 Q가 결합일 때, RQ는 메틸이 아니다.