Inhibitors of histone deacetylaseThis invention relates to compounds and methods for the inhibition of HDAC enzymatic activity. More particularly, the invention provides for compounds of formula (I), (I) and N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, and racemic and scalemic mixtures, diastereomers and enantiomers thereof, wherein L, M, n, R, W, X and Y are as defined in the specification.A kind of compound of formula (i)：with its n- oxides, hydrate, solvate, pharmaceutically acceptable salt, prodrug and compound, and its racemization and non-racemization mixture, dynamic isomer, diastereoisomer and enantiomter, whereinselected from aryl, heteroaryl, cyclic hydrocarbon radical and heterocyclic radical, wherein each aryl, heteroaryl, cyclic hydrocarbon radical and heterocyclyl moieties are optionally substituted；w is selected from n ,-c=and-c (r1)-, wherein whenwhen being cyclic hydrocarbon radical or heterocyclic radical, w is-c (r1)-；m is selected from-c (o) n (r1)or2、-c(o)nr1r2、-c(o)oh、-c(o)or1、-c(o)c1-c3alkyl-sr1、-nhc(o)c1-c3alkyl-sr1、-nhc(o)c1-c3alkyl-or1、-c(o)ch2- s (acetyl group) ,-c (o)-heteroaryl ,-c (o)-heterocyclic radical ,-c (noh) nr1r2、-c(o)c1-c3alkyl-or1、-c(o)c1-c3alkyl-nr1r2、-c(o)cf3、-c(o)c(o)or1、-c(o)c(o)nr1r2、-c(o)c1-c4alkyl ,-n (oh) c (o) h ,-n (or1)c(o)r2、-nr1so2nr1r2、-so2nr1oh、-n(oh)c(o)nr1r2、-nr1c(o)n(oh)r2、-oc(o)n(oh)r2、-c(noh)nr1r2with zn- chelation groups；orwhenit iswhen, m is-c1-c2alkyl-c (o) n (r1)or2；r1and r2independently selected from-h ,-alkyl ,-aryl ,-aryl-aryl ,-heteroaryl, heteroaryl-aryl, heteroaryl-heteroaryl, alkyl-heteroaryl and-alkyl-aryl, wherein each aryl and heteroaryl moieties are optionally substituted；r is selected from h, alkyl, halo, hydroxyl, nitro, c1-c4alkyl ,-nr1r2、-or1, aryl, heteroaryl, oxyl and cf3；n is 0 to 1 integer；l is selected from aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, fused-aryl, annelated heterocycles base, fusion cyclic hydrocarbon radical ,-alkenyl-aryl ,-aryl-heteroaryl ,-heteroaryl-aryl ,-alkynyl-aryl ,-o-c0-c4alkyl-aryl ,-alkyl-aryl-group ,-so2nr1-c0-c4alkyl-aryl ,-nr1- aryl ,-cf3,-the tert-butyl group ,-nr1so2- aryl, halo ,-n (r1) c (o)-aryl ,-s- heteroaryls and-s- aryl, 1 to 3 substituents that wherein each aryl, heteroaryl, cyclic hydrocarbon radical and heterocyclyl moieties are optionally independently selected replace, and each of which is optionally fused on one or more aryl, heterocycle or heteroaryl ring, or one or more saturation or on the undersaturated cyclic hydrocarbon radical in part or heterocyclic ring, each of which ring is optionally substitutedwhereinin cyclic hydrocarbon radical, heterocyclic radical, aryl or heteroaryl groups be connected to optionally by key or by bridging substituent on the cyclic hydrocarbon radical in l, heterocyclic radical, aryl or heteroaryl；y is selected from h, halo ,-aryl-heterocyclic ,-aryl-o-c0-c4alkyl-aryl ,-aryl-aryl ,-c1-c4alkyl, miscellaneous alkyl, alkenyl, alkynyl ,-n (ra)(rb)、-n(rc)(rd)、-ore、-srs、-c0-c3alkyl-aryl ,-c0-c3alkyl-heteroaryl ,-c0-c3alkyl-heterocyclyl ,-c0-c3alkyl-cycloalkyl ,-c2-c4alkenyl-aryl ,-c2-c4alkenyl-heteroaryl ,-c2-c4alkenyl-heterocyclic radical ,-c2-c4alkenyl-cyclic hydrocarbon radical ,-c2-c4alkynyl-aryl ,-c2-c4alkynyl-heteroaryl ,-c2-c4alkynyl-heterocyclic radical ,-c2-c4alkynyl-cyclic hydrocarbon radical ,-o-c0-c3alkyl-aryl ,-o-c0-c3alkyl-heteroaryl ,-o-c0-c3alkyl-cycloalkyl ,-o-c0-c3alkyl-heterocycle alkyl ,-c (o) nh-c0-c3alkyl-aryl ,-c (o) nh-c0-c3alkyl-heteroaryl ,-o-c0-c3alkyl-aryl-aryl ,-o-c0-c3alkyl-heteroaryl-aryl ,-o-c0-c3alkyl-aryl-heteroaryl ,-o-c0-c3alkyl-heteroaryl-heteroaryl ,-s (o)0-2-c0-c3alkyl-aryl ,-s (o)0-2-c0-c3alkyl-heteroaryl-aryl ,-s (o)0-2-c0-c3alkyl-aryl-aryl ,-s (o)0-2-c0-c3alkyl-heteroaryl ,-s (o)0-2-c0-c3alkyl-aryl-heteroaryl ,-s (o)0-2-c0-c3alkyl-heteroaryl-heteroaryl ,-aryl-c0-c3alkyl-aryl ,-heteroaryl-c0-c3alkyl-aryl ,-c0-c3alkyl-aryl-c0-c2alkyl-n (re)-c0-c2alkyl-aryl ,-c0-c3alkyl-aryl-c0-c2alkyl-n (re)-c0-c2alkyl-heteroaryl ,-c0-c3alkyl-heteroaryl-c0-c2alkyl-n (re)-c0-c2alkyl-aryl ,-c0-c3alkyl-heteroaryl-c0-c2alkyl-n (re)-c0-c2alkyl-heteroaryl ,-c0-c3alkyl-aryl-c0-c2alkyl-n (re)-s(o)2-c0-c2alkyl-aryl ,-c0-c3alkyl-aryl-c0-c2alkyl-n (re)-s(o)2-c0-c2alkyl-heteroaryl ,-c0-c3alkyl-heteroaryl-c0-c2alkyl-n (re)-s(o)2-c0-c2alkyl-aryl ,-c0-c3alkyl-heteroaryl-c0-c2alkyl-n (re)-s(o)2-c0-c2alkyl-heteroaryl ,-n (re)-s(o)2-n(rf)h、-n(re)-s(o)2-n(rf)2、-n(re)-c(o)h、-n(re)-c (o) alkyl ,-c (o)-n (re)h、-c(o)-n(re)2、-n(re)-c(o)-n(rf)2、-n(re)-c (o)-o- alkyl ,-o-c (o)-n (re)(rf) ,-oh ,-o- alkyl ,-o- aryl ,-n (re)-c(o)-c2-c4alkyl-ore、-o-c2-c4alkyl-n (re)(rf) ,-heterocyclic radical-c0-c3alkyl-aryl ,-cyclic hydrocarbon radical-c0-c3alkyl-aryl ,-aryl-c0-c3alkyl-heteroaryl ,-heteroaryl-c0-c3alkyl-heteroaryl ,-heterocyclic radical-c0-c3alkyl-heteroaryl ,-cyclic hydrocarbon radical-c0-c3alkyl-heteroaryl ,-aryl-c0-c3alkyl-heterocyclyl ,-heteroaryl-c0-c3alkyl-heterocyclyl ,-heterocyclic radical-c0-c3alkyl-heterocyclyl ,-cyclic hydrocarbon radical-c0-c3alkyl-heterocyclyl ,-heterocyclic radical-c0-c3alkyl-o-c0-c3alkyl-aryl ,-heterocyclic radical-c0-c3alkyl-o-c0-c3alkyl-heteroaryl ,-heterocyclic radical-c0-c3alkyl-o-c (o) nh-c0-c3alkyl-aryl ,-heterocyclic radical-c0-c3alkyl-o-c (o) nh-c0-c3alkyl-heteroaryl ,-heterocyclic radical-c0-c3alkyl-heteroaryl-aryl ,-heterocyclic radical-c0-c3alkyl-heteroaryl-heteroaryl ,-hetero...
히스톤 탈아세틸화효소의 저해물질본 발명은 HDAC 효소 활성의 저해를 위한 화합물 및 방법에 관계한다. 더욱 구체적으로, 본 발명에서는 화학식 (I)의 화합물, N-산화물, 수화물, 용매화합물, 제약학적으로 허용되는 염, 이들의 프로드러그 및 복합체, 그리고 이들의 라세미와 스칼레믹(scalemic) 혼합물, 부분입체이성질체 및 거울상이성질체를 제시한다:  (I) 여기서 L, M, n, R, W, X와 Y는 본 명세서에서 정의된 바와 동일하다.화학식 (I)의 화합물, 또는 이의 N-산화물, 수화물, 용매화합물, 제약학적으로 허용되는 염, 프로드러그 또는 복합체, 또는 이들의 라세미와 스칼레믹(scalemic) 혼합물, 호변이성질체, 부분입체이성질체 또는 거울상이성질체: [이미지] (I)여기서 [이미지]는 아릴, 헤테로아릴, 시클로알킬 및 헤테로시클릴로 구성된 군에서 선택되고, 여기서 각 아릴, 헤테로아릴, 시클로알킬 및 헤테로시클릴 모이어티(moiety)는 선택적으로 치환되고;W는 N, -C= 및 -C(R1)-로 구성된 군에서 선택되고, 여기서 [이미지]이 시클로알킬 또는 헤테로시클릴일 때, W는 -C(R1)-이고;M은 -C(O)N(R1)OR2, -C(O)NR1R2, -C(O)OH, -C(O)OR1, -C(O)C1-C3알킬-SR1, -NHC(O)C1-C3알킬-SR1, -NHC(O)C1-C3알킬-OR1, -C(O)CH2-S(아세틸), -C(O)-헤테로아릴, -C(O)-헤테로시클릴, -C(NOH)NR1R2, -C(O)C1-C3알킬-OR1, -C(O)C1-C3알킬-NR1R2, -C(O)CF3, -C(O)C(O)OR1, -C(O)C(O)NR1R2, -C(O)C1-C4알킬, -N(OH)C(O)H, -N(OR1)C(O)R2, -NR1SO2NR1R2, -SO2NR1OH, -N(OH)C(O)NR1R2, -NR1C(O)N(OH)R2, -OC(O)N(OH)R2, -C(NOH)NR1R2, 그리고 Zn-킬레이트기로 구성된 군에서 선택되고; 또는 [이미지]이 [이미지]일 때, M은 -C1-C2알킬-C(O)N(R1)OR2이고;R1과 R2는 독립적으로, -H, -알킬, -아릴, -아릴-아릴, -헤테로아릴, 헤테로아릴-아릴, 헤테로아릴-헤테로아릴, 알킬-헤테로아릴 및 -알킬-아릴로 구성된 군에서 선택되고, 여기서 각 아릴과 헤테로아릴 모이어티는 선택적으로 치환되고; R은 H, 알킬, 할로, 히드록시, 니트로, C1-C4알킬, -NR1R2, -OR1, 아릴, 헤테로아릴, 알킬옥시 및 CF3으로 구성된 군에서 선택되고;n은 0 내지 1의 정수이고;L은 아릴, 헤테로아릴, 시클로알킬, 헤테로시클릴, 융합된 아릴, 융합된 헤테로시클릴, 융합된 시클로알킬, -알케닐-아릴, -아릴-헤테로아릴, -헤테로아릴-아릴, -알키닐-아릴, -O-C0-C4알킬-아릴, -알킬-아릴, -SO2NR1-C0-C4알킬-아릴, -NR1-아릴, -CF3, -t-Bu, -NR1SO2-아릴, 할로, -N(R1)C(O)-아릴, -S-헤테로아릴 및 -S-아릴로 구성된 군에서 선택되고, 여기서 각 아릴, 헤테로아릴, 시클로알킬 및 헤테로시클릴 모이어티는 1 내지 3개의 독립적으로 선택된 치환기로 선택적으로 치환되고, 그리고 이들 각각은 하나 이상의 아릴, 헤테로환형 또는 헤테로아릴 고리, 또는 하나 이상의 포화된 또는 부분적으로 불포화된 시클로알킬 또는 헤테로시클릴 고리에 선택적으로 융합되고, 각 고리는 선택적으로 치환되고,여기서 [이미지]의 시클로알킬, 헤테로시클릴, 아릴 또는 헤테로아릴 모이어티는 결합에 의해 또는 가교 치환기에 의해, L의 시클로알킬, 헤테로시클릴, 아릴 또는 헤테로아릴에 선택적으로 연결되고;Y는 H, 할로, -아릴-헤테로시클릴, -아릴-O-C0-C4알킬-아릴, -아릴-아릴, -C1-C4알킬, 헤테로알킬, 알케닐, 알키닐, -N(Ra)(Rb), -N(Rc)(Rd), -ORe, -SRs, -C0-C3알킬-아릴, -C0-C3알킬-헤테로아릴, -C0-C3알킬-헤테로시클릴, -C0-C3알킬-시클로알킬, -C2-C4알케닐-아릴, -C2-C4알케닐-헤테로아릴, -C2-C4알케닐-헤테로시클릴, -C2-C4알케닐-시클로알킬, -C2-C4알키닐-아릴, -C2-C4알키닐-헤테로아릴, -C2-C4알키닐-헤테로시클릴, -C2-C4알키닐-시클로알킬, -O-C0-C3알킬-아릴, -O-C0-C3알킬-헤테로아릴, -O-C0-C3알킬-시클로알킬, -O-C0-C3알킬-헤테로시클로알킬, -C(O)NH-C0-C3알킬-아릴, -C(O)NH-C0-C3알킬-헤테로아릴, -O-C0-C3알킬-아릴-아릴, -O-C0-C3알킬-헤테로아릴-아릴, -O-C0-C3알킬-아릴-헤테로아릴, -O-C0-C3알킬-헤테로아릴-헤테로아릴, -S(O)0-2-C0-C3알킬-아릴, -S(O)0-2-C0-C3알킬-헤테로아릴-아릴, -S(O)0-2-C0-C3알킬-아릴-아릴, -S(O)0-2-C0-C3알킬-헤테로아릴, -S(O)0-2-C0-C3알킬-아릴-헤테로아릴, -S(O)0-2-C0-C3알킬-헤테로아릴-헤테로아릴, -아릴-C0-C3알킬-아릴, -헤테로아릴-C0-C3알킬-아릴, -C0-C3알킬-아릴-C0-C2알킬-N(Re)-C0-C2알킬-아릴, -C0-C3알킬-아릴-C0-C2알킬-N(Re)-C0-C2알킬-헤테로아릴, -C0-C3알킬-헤테로아릴-C0-C2알킬-N(Re)-C0-C2알킬-아릴, -C0-C3알킬-헤테로아릴-C0-C2알킬-N(Re)-C0-C2알킬-헤테로아릴, -C0-C3알킬-아릴-C0-C2알킬-N(Re)-S(O)2-C0-C2알킬-아릴, -C0-C3알킬-아릴-C0-C2알킬-N(Re)-S(O)2-C0-C2알킬-헤테로아릴, -C0-C3알킬-헤테로아릴-C0-C2알킬-N(Re)-S(O)2-C0-C2알킬-아릴, -C0-C3알킬-헤테로아릴-C0-C2알킬-N(Re)-S(O)2-C0-C2알킬-헤테로아릴, -N(Re)-S(O)2-N(Rf)H, -N(Re)-S(O)2-N(Rf)2, -N(Re)-C(O)H, -N(Re)-C(O)알킬, -C(O)-N(Re)H, -C(O)-N(Re)2, -N(Re)-C(O)-N(Rf)2, -N(Re)-C(O)-O-알킬, -O-C(O)-N(Re)(Rf), -OH, -O-알킬, -O-아릴, -N(Re)-C(O)-C2-C4알킬-ORe, -O-C2-C4알킬-N(Re)(Rf), -헤테로시클릴-C0-C3알킬-아릴, -시클로알킬-C0-C3알킬-아릴, -아릴-C0-C3알킬-헤테로아릴, -헤테로아릴-C0-C3알킬-헤테로아릴, -헤테로시클릴-C0-C3알킬-헤테로아릴, -시클로알킬-C0-C3알킬-헤테로아릴, -아릴-C0-C3알킬-헤테로시클릴, -헤테로아릴-C0-C3알킬-헤테로시클릴, -헤테로시클릴-C0-C3알킬-헤테로시클릴, -시클로알킬-C0-C3알킬-헤테로시클릴, -헤테로시클릴-C0-C3알킬-O-C0-C3알킬-아릴, -헤테로시클릴-C0-C3알킬-O-C0-C3알킬-헤테로아릴, -헤테로시클릴-C0-C3알킬-O-C(O)NH-C0-C3알킬-아릴, -헤테로시클릴-C0-C3알킬-O-C(O)NH-C0-C3알킬-헤테로아릴, -헤테로시클릴-C0-C3알킬-헤테로아릴-아릴, -헤테로시클릴-C0-C3알킬-헤테로아릴-헤테로아릴, -헤테로시클릴-C0-C3알킬-아릴-아릴, -NHS(O)2-C0-C3알킬-아릴, -NHS(O)2-C0-C3알킬-헤테로아릴, -NHC(O)-C0-C3알킬-아릴, -헤테로시클릴-C0-C3알킬-아릴, -헤테로시클릴-C0-C3알킬-헤테로아릴, -헤테로시클릴-C(O)-헤테로시클릴, -헤테로시클릴-C(O)-O-알킬, -헤테로시클릴-S(O)2-알킬, -헤테로시클릴-S(O)2-C0-C3알킬-아릴, -헤테로시클릴-S(O)2-C0-C3알킬-헤테로아릴, -헤테로시클릴-C1-C4알킬-아릴, -헤테로시클릴-C1-C4알킬-헤테로아릴, -헤테로시클릴-C0-C3알킬-아릴-헤테로아릴, -헤테로시클릴-C0-C3알킬-헤테로아릴-C0-C3알킬-아릴, -헤테로시클릴-C0-C3알킬-헤테로아릴-C0-C3알킬-헤테로아릴, -헤테로시클릴-C0-C3알킬-아릴-C0-C3알킬-아릴, -헤테로시클릴-C0-C3알킬-아릴-C0-C3알킬-헤테로아릴, -헤테로시클릴-S(O)2-C0-C3알킬-아릴, -헤테로시클릴-S(O)2-C0-C3알킬-헤테로아릴, -헤테로시클릴-S(O)2-C0-C3알킬-알킬, -헤테로시클릴-S(O)2-C0-C3알킬-시클로알킬, -헤테로시클릴-S(O)2-C0-C3알킬-헤테로시클릴, -헤테로시클릴-C(O)-C0-C3알킬-아릴, -헤테로시클릴-C(O)-C0-C3알킬-헤테로아릴, -헤테로시클릴-C(O)-C0-C3알킬-알킬, -헤테로시클릴-C(O)-C0-C3알킬-시클로알킬, -헤테로시클릴-C(O)-C0-C3알킬-헤테로시클릴, -헤테로시클릴-C(O)NH-C0-C3알킬-아릴, -헤테로시클릴-C(O)NH-C0-C3알킬-헤테로아릴, -헤테로시클릴-C(O)NH-C0-C3알킬-알킬, -헤테로시클릴-C(O)NH-C0-C3알킬-시클로알킬, -헤테로시클릴-C(O)NH-C0-C3알킬-헤테로시클릴, -헤테로시클릴-C(O)O-C0-C3알킬-아릴, -헤테로시클릴-C(O)O-C0-C3알킬-헤테로아릴, -헤테로시클릴-C(O)O-C0-C3알킬-알킬, -헤테로시클릴-C(O)O-C0-C3알킬-시클로알킬, -헤테로시클릴-C(O)O-C0-C3알킬-헤테로시클릴, -헤테로시클릴-S(O)2-NH-C0-C3알킬-아릴, -헤테로시클릴-S(O)2-NH-C0-C3알킬-헤테로아릴, -헤테로시클릴-S(O)2-NH-C0-C3알킬-알킬, -헤테로시클릴-S(O)2-NH-C0-C3알킬-시클로알킬, -헤테로시클릴-S(O)2-NH-C0-C3알킬-헤테로시클릴, -C0-C3알킬-헤테로시클릴-C2-C4알케닐-아릴, -C0-C3알킬-헤테로시클릴-CH(아릴)2, -C0-C3알킬-헤테로시클릴-CH(헤테로아릴)2, -C0-C3알킬-헤테로시클릴-CH(아릴)(헤테로아릴), -C0-C3알킬-아릴-O-C2-C4알킬-헤테로시클릴, -C0-C3알킬-아릴-C0-C3알킬-헤테로시클릴-C0-C3알킬-아릴, -C0-C3알킬-헤테로아릴-C0-C3알킬-헤테로시클릴-C0-C3알킬-아릴, -C0-C3알킬-아릴-C0-C3알킬-헤테로시클릴-C0-C3알킬-헤테로아릴, -C0-C3알킬-헤테로아릴-C0-C3알킬-헤테로시클릴-C0-C3알킬-헤테로아릴, -NH-C(O)-아릴, -NH-C(O)-헤테로아릴, -CH(아릴)2, -CH(헤테로아릴)2, -C0-C3알킬-아릴-헤테로시클릴, -C0-C3알킬-아릴-헤테로시클릴-S(O)2-아릴, -C0-C3알킬-헤테로아릴-헤테로시클릴-S(O)2-아릴, -C0-C3알킬-아릴-헤테로시클릴-S(O)2-헤테로아릴, -C0-C3알킬-헤테로아릴-헤테로시클릴-S(O)2-헤테로아릴, -C0-C3알킬-아릴-S(O)2-헤테로시클릴-아릴, -C0-C3알킬-헤테로아릴-S(O)2-헤테로시클릴-아릴, -C0-C3알킬-아릴-S(O)2-헤테로시클릴-헤테로아릴, -C0-C3알킬-헤테로아릴-S(O...