Bridged piperazine derivativesA compound of the formula (I) or the pharmaceutically acceptable salt thereof; wherein a, c, d, k, l, m, W, X, Y Z, R, and R are as defined, and useful to treat inflammation and other immune disorders.The compound shown in the structural formula (i) or pharmaceutical salts and prodrug thereof; wherein,a is 1,2,3,4 or 5;c is 0 or 1;d is 1,2,3,4 or 5;k is 0,1,2,3 or 4; l is 0,1,2,3 or 4; m is 0,1,2,3, or 4; k, l and m can not be 0 entirely, if m and/or k are not 0, i is necessary for 0;w is ch or n;x is c (o), c (s) or ch 2y is ch 2z is an oxygen, nr 9or cr 11r 12each r1independently be selected from hydrogen, hydroxyl, hydroxyl sulfonyl, halogen, (c1-c 6) alkyl, sulfydryl, sulfydryl (c1-c 6) alkyl, (c1-c 6) alkyl sulfide, (c1-c 6) alkyl sulphinyl, (c1-c 6) alkyl sulphonyl, (c1-c 6) alkyl sulfide (c1-c 6) alkyl, (c1-c 6) alkyl sulfenyl (c1-c 6) alkyl, (c1-c 6) alkyl sulfonyl (c1-c 6) alkyl, (c1-c 6) alkoxyl, (c6-c 10) aromatic radical oxygen, halogen (c1-c 6) alkyl, trifluoromethyl, formoxyl, formoxyl (c1-c 6) alkyl, nitro, nitroso, cyano group, (c6-c 10) aromatic radical (c1-c 6) alkoxyl, halogen (c1-c 6) alkoxyl, trifluoromethoxy, (c3-c 7) cycloalkyl, (c3-c 7) cycloalkyl (c1-c 6) alkyl, hydroxyl (c3-c 7) cycloalkyl (c1-c 6) alkyl, (c3-c 7) cycloalkyl amino, (c3-c 7) cycloalkyl amino (c1-c 6) alkyl, ((c3-c 7) cycloalkyl) ((c1-c 6) alkyl) amino, ((c3-c 7) cycloalkyl (c1-c 6) alkyl) amino (c1-c 6) alkyl, cyano group (c1-c 6) alkyl, (c2-c 7) thiazolinyl, (c2-c 7) alkynyl, (c6-c 10) aromatic radical, (c6-c 10) aromatic radical (c1-c 6) alkyl, (c6-c 10) aromatic radical (c2-c 6) thiazolinyl, hydroxyl (c1-c 6) alkyl, hydroxyl (c6-c 10) aromatic radical (c1-c 6) alkyl, hydroxyl (c1-c 6) alkyl sulfide (c1-c 6) alkyl, hydroxyl (c2-c 6) thiazolinyl, hydroxyl (c2-c 6) alkynyl, (c1-c 6) alkoxyl (c1-c 6) alkyl, (c1-c 6) alkoxyl (c6-c 10) aromatic radical (c1-c 6) alkyl, (c6-c 10) aromatic radical oxygen (c1-c 6) alkyl, (c6-c 10) aromatic radical (c1-c 6) alkoxyl (c1-c 6) alkyl, amino, (c1-c 6) alkyl amino, ((c1-c 6) alkyl)2amino, (c6-c 10) aromatic radical amino, (c6-c 10) aromatic radical (c1-c 6) alkyl amino, amino (c1-c 6) alkyl, (c1-c 6) alkyl amino (c1-c 6) alkyl, ((c1-c 6) alkyl)2amino (c1-c 6) alkyl, hydroxyl (c1-c 6) alkyl amino (c1-c 6) alkyl, (c6-c 10) amino (c of aromatic radical1-c 6) alkyl, (c6-c 10) aromatic radical (c1-c 6) alkyl amino (c1-c 6) alkyl, (c1-c 6) alkyl-carbonyl-amino, ((c1-c 6) alkyl-carbonyl) ((c1-c 6) alkyl) amino, (c1-c 6) alkyl-carbonyl-amino (c1-c 6) alkyl, ((c1-c 6) alkyl-carbonyl) (c1-c 6) alkyl) amino (c1-c 6) alkyl, (c1-c 6) alkoxycarbonyl amino, ((c1-c 6) alkoxy carbonyl) (c1-c 6) alkyl amino, (c1-c 6) alkoxycarbonyl amino (c1-c 6) alkyl, ((c1-c 6) alkoxy carbonyl) ((c1-c 6) alkyl) amino (c1-c 6) alkyl, carboxyl, (c1-c 6) alkoxy carbonyl, (c6-c 10) aromatic radical (c1-c 6) alkoxy carbonyl, (c1-c 6) alkyl-carbonyl, (c1-c 6) alkyl-carbonyl (c1-c 6) alkyl, (c6-c 10) the aromatic radical carbonyl, (c6-c 10) aromatic radical carbonyl (c1-c 6) alkyl, (c6-c 10) aromatic radical (c1-c 6) alkyl-carbonyl, (c6-c 10) aromatic radical (c1-c 6) alkyl-carbonyl (c1-c 6) alkyl, carboxyl (c1-c 6) alkyl, (c1-c 6) alkoxy carbonyl (c1-c 6) alkyl, (c6-c 10) aromatic radical (c1-c 6) alkoxy carbonyl (c1-c 6) alkyl, (c1-c 6) alkoxyl (c1-c 6) alkyl-carbonyl oxygen (c1-c 6) alkyl, amino carbonyl, (c1-c 6) alkyl amino-carbonyl, ((c1-c 6) alkyl)2amino carbonyl, (c6-c 10) the aromatic radical amino carbonyl, (c6-c 10) aromatic radical (c1-c 6) alkyl amino-carbonyl, amino carbonyl (c1-c 6) alkyl, (c1-c 6) alkyl amino-carbonyl (c1-c 6) alkyl, ((c1-c 6) alkyl)2amino carbonyl (c1-c 6) alkyl, (c6-c 10) aromatic radical amino carbonyl (c1-c 6) alkyl, (c1-c 6) alkyl amino-carbonyl (c1- c 6) alkyl, amidino groups, guanidine radicals, urea groups, (c1-c 6) the alkyl urea groups, ((c1-c 6) alkyl)2urea groups, urea groups (c1-c 6) alkyl, (c1-c 6) alkyl urea groups (c1-c 6) alkyl, ((c1-c 6) alkyl)2urea groups (c1-c 6) alkyl, (c2-c 9) heterocyclylalkyl, (c2-c 9) assorted aromatic radical, (c2-c 9) heterocyclylalkyl (c1-c 6) alkyl and (c2-c 9) assorted aromatic radical (c1-c 6) alkyl;r 4be (r 5q q) f(c 6-c 10) aromatic base, (r 5q q) f(c 3-c 10) cycloalkyl, (r 5q q) f(c 2-c 9) assorted aromatic base, (r 5q q) f(c 2-c 9) heterocyclylalkyl, wherein, f is 0,1,2,3,4 or 5;q is (c 1-c 6) alkyl; q is 0 or 1;r 5be independently selected from: (c2-c 9) the heterocyclylalkyl carbonyl, (c2-c 9) assorted aromatic radical carbonyl, (c2-c 9) assorted aromatic radical (c1-c 6) alkyl amino-carbonyl, (c2-c 9) assorted aromatic radical amino carbonyl, (c2-c 9) heterocyclylalkyl (c1-c 6) alkyl amino-carbonyl, (c1-c 6) the alkyl sulfonyl-amino carbonyl, (c1-c 6) alkyl sulfonyl-amino (c1-c 6) alkyl amino-carbonyl, urea groups (c1-c 6) alkyl amino-carbonyl, (c1-c 6) alkyl urea groups (c1- c 6) alkyl amino-carbonyl, ((c1-c 6) alkyl)2urea groups (c1-c 6) alkyl amino-carbonyl, halogen (c1-c 6) alkyl amino-carbonyl, (c1-c 6) alkyl-carbonyl-amino (c1-c 6) alkyl amino-carbonyl, hydroxyl (c1-c 6) alkyl amino-carbonyl, aminosulfonyl (c1-c 6) alkyl amino-carbonyl, carboxyl (c1-c 6) alkyl amino-carbonyl, (c1- c 6) alkyl sulfonyl amino (c1-c 6) alkyl...
브리지된 피페라진 유도체본 발명은 화학식 (I)의 화합물 및 그의 제약학적으로 허용가능한 염(여기서, a, c, d, k, l, m, W, X, Y Z, R1, 및 R4 는 정의한 바와 같다)에 관한 것으로 상기 화합물은 염증 및 기타 면역성 질환에 유용하다.하기 화학식(I)의 화합물 또는 그의 제약학적으로 허용가능한 염 또는 전구약물: <화학식 I> [이미지] 상기식에서, a는 1, 2, 3, 4 또는 5이고; c는 0 또는 1이고; d는 1, 2, 3, 4 또는 5이고; k는 0, 1, 2, 3 또는 4이고; l은 0, 1, 2, 3 또는 4이고; m은 0, 1, 2, 3, 또는 4이고; k, l 및 m은 모두 0일 수는 없으며, m 및/또는 k가 0이 아닌 경우엔 l은 O이어야 하고; W는 CH 또는 N이고; X는 C(O), C(S) 또는 CH2이고; Y는 CH2이고; Z는 산소, NR9 또는 CR11R12이고; R1은 각각 수소, 히드록시, 히드록시술포닐, 할로, (C1-C6)알킬, 머캅토, 머캅토(C1-C6)알킬, (C1-C6)알킬티오, (C1-C6 )알킬술피닐, (C1-C6)알킬술포닐, (C1-C6)알킬티오(C1-C6 )알킬, (C1-C6)알킬술피닐(C1-C6 )알킬, (C1-C6)알킬술포닐(C1-C6)알킬, (C1-C6)알콕시, (C6-C10)아릴옥시, 할로(C1-C6 )알킬, 트리플루오로메틸, 포르밀, 포르밀(C1-C6)알킬, 니트로, 니트로소, 시아노, (C6-C10)아릴(C 1-C6)알콕시, 할로(C1-C6)알콕시, 트리플루오로메톡시, (C3-C7)시클로알킬, (C3-C7)시클로알킬(C 1-C6)알킬, 히드록시(C3-C7)시클로알킬(C1-C6)알킬, (C3-C7 )시클로알킬아미노, (C3-C7)시클로알킬아미노(C1-C6)알킬, ((C3-C7)시클로알킬)((C1-C6 )알킬)아미노, ((C3-C7)시클로알킬(C1-C6)알킬)아미노(C1-C6)알킬, 시아노(C1-C6)알킬, (C2-C 7)알케닐, (C2-C7)알키닐, (C6-C10)아릴(C1-C6), 아릴(C1-C6)알킬, (C6-C10)아릴(C 2-C6)알케닐, 히드록시(C1-C6)알킬, 히드록시(C6-C10)아릴(C1-C6)알킬, 히드록시(C1-C6 )알킬티오(C1-C6)알킬, 히드록시(C2-C6)알케닐, 히드록시(C2-C6)알키닐, (C1-C6)알콕시(C1-C 6)알킬, (C1-C6)알콕시(C6-C10)아릴 (C1-C6)알킬, (C6-C10)아릴옥시(C1-C6)알킬, (C6-C10)아릴(C1-C6)알콕시(C1-C6)알킬, 아미노, (C1-C6)알킬아미노, ((C1-C6)알킬)2아미노, (C6-C10)아릴아미노, (C6-C10)아릴-(C1-C6)알킬아미노, 아미노(C1-C6)알킬, (C1-C6 )알킬아미노(C1-C6)알킬, ((C1-C6)알킬)2아미노(C1-C6)알킬, 히드록시(C1-C6)알킬아미노(C1-C 6)알킬, (C6-C10)아릴아미노(C1-C6)알킬, (C6-C10)아릴 (C1-C6)알킬아미노(C1-C6 )알킬, (C1-C6)알킬카르보닐아미노, ((C1-C6)알킬카르보닐)((C1-C6)알킬)아미노, (C1-C6)알킬카르보닐아미노(C 1-C6)알킬, ((C1-C6)알킬카르보닐)((C1-C6)알킬)아미노(C1-C 6)알킬, (C1-C6)알콕시카르보닐아미노, (C1-C6)알콕시카르보닐(C1-C6)알킬아미노, (C1-C 6)알콕시카르보닐아미노(C1-C6)알킬, (C1-C6)알콕시카르보닐((C1-C6)알킬)아미노(C1-C 6)알킬, 카르복시, (C1-C6)알콕시카르보닐, (C6-C10)아릴(C1-C6)알콕시카르보닐, (C1-C 6)알킬카르보닐, (C1-C6)알킬카르보닐(C1-C6)알킬, (C6-C10)아릴카르보닐, (C6-C 10)아릴카르보닐(C1-C6)알킬, (C6-C10)아릴(C1-C6)알킬카르보닐, (C6-C10)아릴(C1-C6 )알킬카르보닐(C1-C6)알킬, 카르복시(C1-C6)알킬, (C1-C6)알콕시카르보닐(C1-C6)알킬, (C6-C 10)아릴(C1-C6)알콕시카르보닐(C1-C6)알킬, (C1-C6)알콕시(C1-C6)알킬카르보닐옥시(C1-C 6)알킬, 아미노카르보닐, (C1-C6)알킬아미노카르보닐, ((C1-C6)알킬)2아미노카르보닐, (C6-C10 )아릴아미노카르보닐, (C6-C10)아릴(C1-C6)알킬아미노카르보닐, 아미노카르보닐(C1-C6 )알킬, (C1-C6)알킬아미노카르보닐(C1-C6)알킬, ((C1-C6)알킬)2아미노카르보닐(C 1-C6)알킬, (C6-C10)아릴아미노카르보닐(C1-C6)알킬, (C1-C6)알킬아미노카르보닐(C1-C 6)알킬, 아미디노, 구아니디노, 우레이도, (C1-C6)알킬우레이도, ((C1-C6)알킬)2우레이도, 우레이도(C1-C6)알킬, (C1-C6)알킬우레이도(C1-C6)알킬, ((C1-C6)알킬)2 우레이도(C1-C6)알킬, (C2-C9)헤테로시클로알킬, (C2-C9)헤테로아릴, (C2-C9)헤테로시클로알킬(C1 -C6)알킬 및 (C2-C9)헤테로아릴(C1-C6)알킬로 부터 독립적으로 선택되고; R4는 (R5Qq)f(C6-C10)아릴, (R5 Qq)f(C3-C10)시클로알킬, (R5Qq) f(C2-C9)헤테로아릴, (R5Qq)f(C2-C9)헤테로시클로알킬인데, 여기서, f는 0, 1, 2, 3, 4 또는 5이고, Q는 (C1-C6)알킬이고, q는 0 또는 1이고, R5는 (C2-C9)헤테로시클로알킬카르보닐, (C2-C9)헤테로아릴카르보닐, (C2-C9)헤테로아릴(C1-C6)알킬아미노카르보닐, (C2-C9)헤테로아릴아미노카르보닐, (C2-C9)-헤테로시클로알킬(C1-C6)알킬아미노카르보닐, (C1-C6)알킬술포닐아미노카르보닐, (C1-C6)알킬술포닐아미노(C1-C6)알킬아미노카르보닐, 우레이도(C1-C6)알킬아미노카르보닐, (C1-C6)알킬우레이도(C1-C6)알킬아미노카르보닐, ((C1-C6)알킬)2우레이도(C1-C6)알킬아미노카르보닐, 할로(C1-C6)알킬아미노카르보닐, (C1-C6)알킬카르보닐아미노(C1-C6)알킬아미노카르보닐, 히드록시(C1-C6)알킬아미노카르보닐, 아미노술포닐(C1-C6)알킬아미노카르보닐, 카르복시(C1-C6)알킬아미노카르보닐, (C1-C6)알킬아미노술포닐(C1-C6)알킬아미노카르보닐, 아미노(C1-C6)알킬카르보닐아미노, (C1-C6)알킬아미노(C1-C6)알킬카르보닐아미노, 카르복시(C1-C6)알킬카르보닐아미노, 카르복시-(C1-C6)알콕시카르보닐아미노, ((C1-C6)알킬)2아미노(C 1-C6)알킬카르보닐아미노, 아세틸아미노(C1-C6)알킬카르보닐아미노, (아세틸)((C1-C6)알킬)아미노(C 1-C6)알킬카르보닐아미노, (C1-C6)알킬술포닐아미노(C1-C6)알킬카르보닐아미노, 시아노구아니디노 (C1-C6)알킬카르보닐아미노, (C1-C6)알킬시아노구아니디노(C 1-C6)알킬카르보닐아미노, ((C1-C6)알킬)2시아노구아니디노(C1-C6)알킬카르보닐아미노, 아미노카르보닐(C1-C6)알킬카르보닐아미노, 아미노카르보닐아미노(C1-C6)알킬카르보닐아미노, (C1-C 6)알킬아미노카르보닐아미노(C1-C6)알킬카르보닐아미노, ((C1-C6)알킬) 2아미노카르보닐-아미노(C1-C6)알킬카르보닐아미노, (C2-C9)헤테로아릴(C1-C 6)알킬카르보닐아미노, (C2-C9)헤테로시클로알킬(C1-C6)알킬카르보닐아미노, 아미노술포닐(C1-C6 )알킬카르보닐아미노, 히드록시(C1-C6)알킬우레이도, 아미노(C1-C6)알킬우레이도, (C1-C6)알킬아미노-(C1-C6)알킬우레이도, ((C1-C6)알킬)2아미노(C1 -C6)알킬우레이도, (C2-C9)헤테로시클로알킬(C1-C6)알킬우레이도, (C2-C9)헤테로아릴우레이도, (C2 -C9)헤테로아릴(C1-C6)알킬우레이도, (C1-C6)알킬술포닐우레이도, 아미노술포닐(C1-C6)알킬우레이도, 아미노카르보닐(C1-C6)알킬우레이도, (C1-C6)알킬아미노카르보닐(C1 -C6)알킬우레이도, ((C1-C6)알킬)2아미노카르보닐(C1-C6)알킬우레이도, 아세틸아미노(C 1-C6)알킬우레이도, (아세틸)((C1-C6)알킬)아미노(C1-C6)알킬우레이도, 카르복시(C 1-C6)알킬우레이도, 할로-(C1-C6)알킬술포닐아미노, 아미노(C1-C6)알킬술포닐아미노, (C1-C6)알킬아미노(C1-C6)알킬술포닐아미노, ((C1-C6)알킬)2아미노(C1-C6)알킬술포닐아미노, 아세틸아미노(C1-C6)알킬술포닐아미노, (아세틸)((C1-C6)알킬)아미노(C1-C6 )알킬술포닐아미노, 우레이도(C1-C6)알킬술포닐아미노, (C1-C6)알킬우레이도(C1-C 6)알킬술포닐아미노, ((C1-C6)알킬)2우레이도(C1-C6)알킬술포닐아미노, (C1-C6)알킬술포닐아미노(C 1-C6)알킬술포닐아미노, 시아노구아니디노(C1-C6)알킬술포닐아미노, 카르복시(C1-C6 )알킬술포닐아미노, (C1-C6)알킬시아노구아니디노(C1-C6)알킬술포닐아미노, ((C1-C6)알킬)2시아노구아니디노(C1-C6)알킬술포닐아미노, 아미노카르보닐(C1-C6)알킬술포닐아미노, (C1-C6)알콕시카르보닐아미노(C1-C6)알킬술포닐아미노, 아미노술포닐아미노카르보닐, (C1 -C6)알킬아미노술포닐아미노카르보닐, ((C1-C6)알킬)2아미노술포닐아미노카르보닐, (C6-C10)아릴술포닐, (C1-C6)알킬아미노술포닐아미노, ((C1-C6 )알킬)2아미노술포닐아미노, 아미노카르보닐(C1-C6)알킬아미노(C1-C6)알킬술포닐아미노, (C2-C9)헤테로시클로알킬옥시카르보닐아미노(C1-C6)알킬술포닐아미노, (C2-C9)헤테로아릴옥시카르보닐아미노- (C1-C6)알킬술포닐아미노, 시아노구아니디노, (C1-C6)알킬시아노구아니디노, ((C1-C6)알킬)2시아노구아니디노, (C2-C9)헤테로시클로알킬시아노구아니디노, (C 2-C9)헤테로시클로알킬(C1-C6)알킬시아노구아니디노, (C2-C9)헤테로아릴(C 1-C6)알킬시아노구아니디노, 아미노(C1-C6)알킬시아노구아니디노, (C1-C6)알킬아미노(C 1-C6)알킬시아노구아니디노, ((C1-C6)알킬)2아미노(C1-C6)알킬시아노구아니디노, 아미노카르보닐(C1-C6)알킬시아노구아니디노, 카르복시(C1-C6)알킬시아노구아니디노, (C1-C6 )알킬아미노카르보닐(C1-C6)알킬시아노구아니디노, ((C1-C6)알킬)2아미노카르보닐(C 1-C6)알킬시아노구아니디노, 히드록시(C1-C6)알킬아미노, 아미노카르보닐(C1-C6)알킬아미노, 카르복시-(C1-C6)알킬아미노, (C1-C6)알킬술포닐아미노(C1-C 6)알킬아미노, (C1-C6)알콕시카르보닐아미노(C1-C6)알킬아미노, 아미노술포닐(C1-C6)알킬아...