Novel piperazine derivativesA compound of formula (I) or the pharmaceutically acceptable salt thereof; wherein a, b, c, d, e, j, R, R, R, and R are as defined above useful to treat inflammation and other immune disorders.Method for preparing a kind of compound or its pharmacy acceptable salt of following formula: wherein: a is 1,2,3,4 or 5;b is 0,1,2,3 or 4;c is 0 or 1;d is 1,2,3,4 or 5;e is 0 or 1;j is 1,2,3, or 4;x is c (o), c (s) or ch 2y is ch 2if perhaps e is 0, then y is chr 8, r wherein 8be hydrogen, (c 6-c 10) aryl or nr 9r 10z is an oxygen, nr 9or cr 11r 12mei r1be independently selected from qing, qiang base, qiang base sulfonyl, halogen, (c1-c 6) the wan base, qiu base, qiu base (c1-c 6) the wan base, (c1-c 5) the alkyl sulfide base, (c1-c 6) wan base sulfinyl, (c1-c 6) wan base sulfonyl, (c1-c 6) alkyl sulfide base (c1-c 6) the wan base, (c1-c 6) wan base sulfinyl (c1-c 6) the wan base, (c1-c 6) wan base sulfonyl (c1-c 6) the wan base, (c1-c 6) the alcoxyl base, (c6-c 10) aryloxy, halo (c1-c 6) the wan base, trifluoromethyl, formoxyl, formoxyl (c1-c 6) the wan base, xiao base, nitrous base, qing base, (c6-c 10) aryl (c1-c 6) the alcoxyl base, halo (c1-c 6) the alcoxyl base, trifluoro methoxyl group, (c3-c 7) cycloalkyl, (c3-c 7) cycloalkyl (c1-c 6) the wan base, qiang base (c3-c 7) cycloalkyl (c1-c 6) the wan base, (c3-c 7) cycloalkyl amino, (c3-c 7) amino (c of cycloalkyl1-c 6) the wan base, ((c3-c 7) cycloalkyl) ((c1-c 6) the wan yl) amino, ((c3-c 7) cycloalkyl (c1-c 6) the wan yl) amino (c1-c 6) the wan base, qing base (c1-c 6) the wan base, (c2-c 7) alkenyl, (c2-c 7) alkynyl group, (c6-c 10) aryl, (c6-c 10) aryl (c1-c 6) the wan base, (c6-c 10) aryl (c2-c 6) alkenyl, qiang base (c1-c 6) the wan base, qiang base (c6-c 10) aryl (c1-c 6) the wan base, qiang base (c1-c 6) wan sulfenyl (c1-c 6) the wan base, qiang base (c2-c 6) alkenyl, qiang base (c2-c 6) alkynyl group, (c1-c 6) alcoxyl base (c1-c 6) the wan base, (c1-c 6) alcoxyl base (c6-c 10) aryl (c1-c 6) the wan base, (c6-c 10) aryloxy (c1-c 6) the wan base, (c6-c 10) aryl (c1-c 6) alcoxyl base (c1-c 6) the wan base, amino, (c1-c 6) wan base amino, ((c1-c 6) the wan yl)2amino, (c6-c 10) aryl amino, (c6-c 10) aryl (c1-c 6) wan base amino, amino (c1-c 6) the wan base, (c1-c 6) amino (c of wan base1-c 6) the wan base, ((c1-c 6) the wan yl)2amino (c1-c 6) the wan base, qiang base (c1-c 6) amino (c of wan base1-c 6) the wan base, (c6-c 10) amino (c of aryl1-c 6) the wan base, (c6-c 10) aryl (c1-c 6) amino (c of wan base1-c 6) the wan base, (c1-c 6) wan base tang base amino, ((c1-c 6) wan base tang yl) ((c1-c 6) the wan yl) amino, (c1-c 6) amino (c of wan base tang base1-c 6) the wan base, ((c1-c 6) wan base tang yl) ((c1-c 6) the wan yl) amino (c1-c 6) the wan base, (c1-c 6) alcoxyl base tang base amino, (c1-c 6) alcoxyl base tang base (c1-c 6) wan base amino, (c1-c 6) amino (c of alcoxyl base tang base1-c 6) the wan base, (c1-c 6) alcoxyl base tang base ((c1-c 6) the wan yl) amino (c1-c 6) the wan base, suo base, (c1-c 6) alcoxyl base tang base, (c6-c 10) aryl (c1-c 6) alcoxyl base tang base, (c1-c 6) wan base tang base, (c1-c 6) wan base tang base (c1-c 6) the wan base, (c6-c 10) aryl tang base, (c6-c 10) aryl tang base (c1-c 6) the wan base, (c6-c 10) aryl (c1-c 6) wan base tang base, (c6-c 10) aryl (c1-c 6) wan tang base (c1-c 6) the wan base, suo base (c1-c 6) the wan base, (c1-c 6) alcoxyl base tang base (c1-c 6) the wan base, (c6-c 10) aryl (c1-c 6) alcoxyl base tang base (c1-c 6) the wan base, (c1-c 6) alcoxyl base (c1-c 6) wan base ketonic oxygen base (c1-c 6) the wan base, amino tang base, (c1-c 6) the amino tang base of wan base, ((c1-c 6) the wan yl)2amino tang base, (c6-c 10) aromatic yl aminocarbonyl, (c6-c 10) aryl (c1-c 6) the amino tang base of wan base, amino tang base (c1-c 6) the wan base, (c1-c 6) the amino tang base of wan base (c1-c 6) the wan base, ((c1-c 6) the wan yl)2amino tang base (c1-c 6) the wan base, (c6-c 10) aromatic yl aminocarbonyl (c1-c 6) the wan base, (c1-c 6) the amino tang base of wan base (c1-c 6) the wan base, mi base, gua base, niao base, (c1-c 6) the ureine base, ((c1-c 6) the wan yl)2the niao base, niao base (c1-c 6) the wan base, (c1-c 6) ureine base (c1-c 6) the wan base, ((c1-c 6) the wan yl)2niao base (c1-c 6) the wan base, (c2-c 9) the za cycloalkyl, (c2-c 9) heteroaryl, (c2-c 9) za cycloalkyl (c1-c 6) wan base and (c2-c 9) heteroaryl (c1-c 6) the wan base;mei r2and r3be independently selected from: yang, halogen, (c1-c 6) the wan base, (c3-c 8) cycloalkyl, (c3-c 8) cycloalkyl (c1-c 6) the wan base, (c3-c 8) amino (c of cycloalkyl1-c 6) the wan base, (c3-c 8) cycloalkyl (c1-c 6) amino (c of wan base1-c 6) the wan base, halo (c1-c 6) the wan base, (c2-c 6) alkenyl, (c2-c 6) alkynyl group, (c6-c 10) aryl, (c6-c 10) aryl (c1-c 6) the wan base, (c6-c 10) aryl (c2-c 6) alkenyl, h-c (o)-, h-c (o)-(c1-c 6) the wan base, qiang base (c1-c 6) the wan base, qiang base (c2-c 6) alkenyl, qiang base (c2-c 6) alkynyl group, qiang base (c6-c 10) aryl (c1-c 6) the wan base, qiang base (c3-c 8) cycloalkyl (c1-c 6) the wan base, sulfenyl (c1-c 6) the wan base, qing base (c1-c 6) the wan base, halo (c1-c 6) amino (c of wan base ...
신규한 피페라진 유도체 본 발명은 염증 및 기타 면역 질환을 치료하는데 유용한 하기 화학식 I의 화합물 또는 그의 약학적으로 허용가능한 염에 관한 것이다: 화학식 I  상기 식에서, a, b, c, d, e, j, R1, R2, R3 및 R4는 명세서에서 정의된 바와 같다.탄산칼륨, 요오드화칼륨 및 비양성자성 용매(예: 부타논)의 존재하에서 하기 식 X의 화합물을 식 H-(Z)e-R4의 화합물(여기서, e는 1이고, Z는 산소이다)과 반응시킴으로써 상응하는 하기 화학식 I의 화합물로 전환시키고, 반응물을 약 4 내지 약 8시간 동안 가열하여 환류시키는 것을 포함하는, 화학식 I의 화합물 또는 그의 약학적으로 허용가능한 염의 제조방법: [이미지] 화학식 I [이미지] 상기 식에서, a는 1, 2, 3, 4 또는 5이고; b는 0, 1, 2, 3 또는 4이고; c는 0 또는 1이고; d는 1, 2, 3, 4 또는 5이고; e는 0 또는 1이고; j는 1, 2, 3 또는 4이고; X는 C(O), C(S) 또는 CH2이고; Y는 CH2, 또는 e가 0이면, Y는 CHR8(여기서, R8은 수소, (C6-C 10)아릴 또는 NR9R10이다)이고; Z는 산소, NR9 또는 CR11R12이고; R1은 각각 독립적으로 수소, 하이드록시, 하이드록시설포닐, 할로, (C1-C6)알킬, 머캅토, 머캅토(C1-C6)알킬, (C1-C6)알킬티오, (C1-C 6)알킬설피닐, (C1-C6)알킬설포닐, (C1-C6)알킬티오(C1-C6)알킬, (C1-C6)알킬설피닐(C 1-C6)알킬, (C1-C6)알킬설포닐(C1-C6)알킬, (C1-C6)알콕시, (C6-C10)아릴옥시, 할로(C1-C 6)알킬, 트리플루오로메틸, 포르밀, 포르밀(C1-C6)알킬, 니트로, 니트로소, 시아노, (C6-C10)아릴(C 1-C6)알콕시, 할로(C1-C6)알콕시, 트리플루오로메톡시, (C3-C7)사이클로알킬, (C3-C7)사이클로알킬(C1-C6)알킬, 하이드록시(C3-C 7)사이클로알킬(C1-C6)알킬, (C3-C7)사이클로알킬아미노, (C3-C7)사이클로알킬아미노(C1-C6)알킬, ((C3-C7)사이클로알킬(C1-C6)알킬)아미노, ((C3-C7)사이클로알킬(C1-C6)알킬)아미노(C1-C6 )알킬, 시아노(C1-C6)알킬, (C2-C7)알케닐, (C2-C7)알키닐, (C6-C10)아릴, (C6-C10 )아릴(C1-C6)알킬, (C6-C10)아릴(C2-C6 )알케닐, 하이드록시(C1-C6)알킬, 하이드록시(C6-C10)아릴(C1 -C6)알킬, 하이드록시(C1-C6)알킬티오(C1-C6)알킬, 하이드록시(C2-C6)알케닐, 하이드록시(C 2-C6)알키닐, (C1-C6)알콕시(C1-C6)알킬, (C1-C6)알콕시(C6-C10)아릴(C 1-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)2 아미노(C1-C6)알킬, 하이드록시(C1-C6)알킬아미노(C1-C6)알킬, (C6-C10)아릴아미노(C1-C6 )알킬, (C6-C10)아릴(C1-C6)알킬아미노(C1-C6)알킬, (C1-C6)알킬카보닐아미노, ((C1-C6)알킬카보닐)((C1-C6)알킬)아미노, (C1-C6)알킬카보닐아미노(C1 -C6)알킬, ((C1-C6)알킬카보닐)((C1-C6)알킬)아미노(C1-C6)알킬, (C1-C6 )알콕시카보닐아미노, ((C1-C6)알콕시카보닐)(C1-C6)알킬아미노, (C1-C6)알콕시카보닐아미노(C1 -C6)알킬, ((C1-C6)알콕시카보닐)((C1-C6)알킬아미노(C1-C6)알킬, 카복시, (C1-C 6)알콕시카보닐, (C6-C10)아릴(C1-C6)알콕시카보닐, (C1-C6)알킬카보닐, (C1-C6)알킬카보닐(C1 -C6)알킬, (C6-C10)아릴카보닐, (C6-C10)아릴카보닐(C1-C6)알킬, (C6-C10 )아릴(C1-C6)알킬카보닐, (C6-C10)아릴(C1-C6)알킬카보닐(C1-C6)알킬, 카복시(C1-C6)알킬, (C1-C6)알콕시카보닐(C1-C6)알킬, (C6-C10)아릴(C1-C6)알콕시카보닐(C1-C6)알킬, (C1 -C6)알콕시(C1-C6)알킬카보닐옥시(C1-C6)알킬, 아미노카보닐, (C1-C6)알킬아미노카보닐, ((C1-C6)알킬) 2아미노카보닐, (C6-C10)아릴아미노카보닐, (C6-C10)아릴(C1-C6)알킬아미노카보닐, 아미노카보닐(C1-C6)알킬, (C1-C6)알킬아미노카보닐(C1-C6)알킬, ((C1-C 6)알킬)2아미노카보닐(C1-C6)알킬, (C6-C10)아릴아미노카보닐(C1-C6)알킬, (C1-C6 )알킬아미노카보닐(C1-C6)알킬, 아미디노, 구아니디노, 우레이도, (C1-C6)알킬우레이도, ((C1-C6)알킬) 2우레이도, 우레이도(C1-C6)알킬, (C1-C6)알킬우레이도(C1-C 6)알킬, ((C1-C6)알킬)2우레이도(C1-C6)알킬, (C2-C9)헤테로사이클로알킬, (C2-C9)헤테로아릴, (C2-C9)헤테로사이클로알킬(C1-C6)알킬 및 (C2-C 9)헤테로아릴(C1-C6)알킬로부터 선택되고; R2 및 R3는 각각 독립적으로 옥소, 할로, (C1-C6)알킬, (C3 -C8)사이클로알킬, (C3-C8)사이클로알킬(C1-C6)알킬, (C3-C8)사이클로알킬아미노(C1 -C6)알킬, (C3-C8)사이클로알킬(C1-C6)알킬아미노(C1-C6)알킬, 할로(C1-C6 )알킬, (C2-C6)알케닐, (C2-C6)알키닐, (C6-C10)아릴, (C6-C10)아릴(C1-C6)알킬, (C6-C10)아릴(C2-C6)알케닐, H-C(O)-, H-C(O)-(C1-C6)알킬, 하이드록시(C1-C6)알킬, 하이드록시(C2-C 6)알케닐, 하이드록시(C2-C6)알키닐, 하이드록시(C6-C10)아릴(C1-C6)알킬, 하이드록시(C3 -C8)사이클로알킬(C1-C6)알킬, 티오(C1-C6)알킬, 시아노(C1-C6)알킬, 할로(C1-C 6)알킬카보닐아미노(C1-C6)알킬, (C1-C6)알콕시(C6-C10)아릴(C1-C6)알킬, (C1-C6)알콕시(C1-C6)알킬, (C6-C10)아릴옥시(C1-C6)알킬, (C6-C10)아릴(C 1-C6)알콕시(C1-C6)알킬, (C1-C6)알킬티오(C1-C6)알킬, (C1-C6)알킬설피닐(C 1-C6)알킬, (C1-C6)알킬설포닐(C1-C6)알킬, 하이드록시(C1-C6)알킬티오(C1-C6)알킬, 아미노(C1 -C6)알킬, (C1-C6)알킬아미노(C1-C6)알킬, ((C1-C6)알킬) 2아미노(C1-C6)알킬, (C6-C10)아릴아미노(C1-C6)알킬, (C6-C10)아릴(C 1-C6)알킬아미노(C1-C6)알킬, (C1-C6)알킬카보닐아미노(C1-C6)알킬, 아지도(C1-C6)알킬, 아미노카보닐아미노(C 1-C6)알킬, (C1-C6)알킬아미노카보닐아미노(C1-C6)알킬, ((C1-C 6)알킬)2아미노카보닐아미노(C1-C6)알킬, (C1-C6)알콕시카보닐(C1-C6)알킬아미노카보닐아미노(C 1-C6)알킬, (C1-C6)알콕시카보닐아미노(C1-C6)알킬, 하이드록시((C1-C6)알킬아미노(C 1-C6)알킬, (C6-C10)아릴옥시(C1-C6)알킬카보닐옥시(C1-C6)알킬, (C1-C6 )알콕시(C1-C6)알킬카보닐옥시(C1-C6)알킬, (C6-C10)아릴(C1-C6)알콕시(C1-C6)알킬카보닐옥시(C 1-C6)알킬, (C1-C6)알킬카보닐, (C1-C6)알킬카보닐(C1-C6)알킬, 카복시, (C1-C6 )알콕시카보닐, (C6-C10)아릴(C1-C6)알콕시카보닐, (C6-C10)아릴(C1-C6)알킬카보닐, 아미노카보닐, (C 1-C6)알킬아미노카보닐, ((C1-C6)알킬)2아미노카보닐, (C6-C10)아릴아미노카보닐, (C6-C10)아릴(C1-C6)알킬아미노카보닐, 카복시(C1-C6)알킬, (C1-C6)알콕시카보닐(C1 -C6)알킬, (C6-C10)아릴(C1-C6)알콕시카보닐(C1-C6)알킬, 아미노카보닐(C1-C6)알킬, (C1 -C6)알킬아미노카보닐(C1-C6)알킬, ((C1-C6)알킬)2아미노카보닐(C1-C6)알킬, (C 6-C10)아릴아미노카보닐(C1-C6)알킬, (C6-C10)아릴(C1-C6)알킬아미노카보닐(C1-C6 )알킬, (C6-C10)아릴설포닐, (C2-C9)헤테로사이클로알킬, (C2-C9)헤테로아릴, (C2-C9)헤테로사이클로알킬(C 1-C6)알킬, (C2-C9)헤테로아릴(C1-C6)알킬 또는 R14R15N(C1-C6)알킬(여기서, R14 및 R15는 각각 독립적으로 (C1-C6)알킬 또는 (C1-C6)알킬카보닐이다)로부터 선택되고; R4는 (R5)f(R6)g(C6-C10)아릴, (R5)f(R6)g(C3-C10)사이클로알킬, (R 5)f(R7)h(C2-C9)헤테로아릴 또는 (R5)f(R7)h(C2-C9)헤테로사이클로알킬이되, 여기서, f는 1, 2, 3 또는 4이고, g 및 h는 각각 독립적으로 0, 1, 2 또는 3이고; R5는 (C2-C9)헤테로사이클로알킬카보닐, (C2-C9)헤테로아릴카보닐, (C2-C9)헤테로아릴(C1-C6)알킬아미노카보닐, (C2-C 9)헤테로사이클로알킬(C1-C6)알킬아미노카보닐, (C1-C6)알킬설포닐아미노(C1-C6)알킬아미노카보닐, 우레이도(C1-C6)알킬아미노카보닐, (C1-C6)알킬우레이도(C1-C6)알킬아미노카보닐, ((C1-C6)알킬)2우레이도(C1-C6)알킬아미노카보닐, 할로(C1-C6)알킬아미노카보닐, 아미노설포닐(C1-C6)알킬아미노카보닐, (C1-C6)알킬아미노설포닐(C 1-C6)알킬아미노카보닐, (C1-C6)알킬설포닐아미노(C1-C6)알킬카보닐아미노, 시아노구아니디노(C 1-C6)알킬카보닐아미노, (C1-C6)알킬시아노구아니디노(C1-C6)알킬카보닐아미노, ((C1-C6)알킬)2시아노구아니디노(C1-C6)알킬카보닐아미노, 아미노카보닐(C1-C6)알킬카보닐아미노, (C2-C9)헤테로아릴(C1-C6)알킬카보닐아미노, (C2-C9)헤테로사이클로알킬(C 1-C6)알킬카보닐아미노, 아미노설포닐(C1-C6)알킬카보닐아미노, 하이드록시(C1-C6 )알킬우레이도, 아미노(C1-C6)알킬우레이도, (C1-C6)알킬아미노(C1-C 6)알킬우레이도, ((C1-C6)알킬)2아미노(C1-C6)알킬우레이도, (C2-C9)헤테로사이클로알킬(C1 -C6)알킬우레이도, (C2-C9)헤테로아릴(C1-C6)알킬우레이도, 아미노설포닐(C1-C6)알킬우레이도, 아미노카보닐(C1...