Inhibitors of histone deacetylaseThe invention relates to compounds for the inhibition of histone deacetylase. More particularly, the invention provides for compounds of formula compounds of the Formula (I) and N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, and racemic and scalemic mixtures, diastereomers and enantiomers thereof, wherein groups L, M, X and Y are as defined herein.A formula (i) compound:and n-oxide compound, hydrate, solvate, pharmaceutically useful salt, prodrug and mixture, and racemic mixture and be mixed thing, diastereomer and enantiomer, whereinm be selected from alkyl ,-n (r e) or s,-cf 3,-c (o) n (r e) (r f) ,-heteroaryl ,-h ,-oh ,-c (o) or e,-ch 2-s (ethanoyl) ,-ch 2-sr ewith-heterocyclylalkyl; x is selected from ch, c (oh), c (c 1-c 4alkyl), c (halogen), c (aryl), c (heteroaryl), c (r c), wherein *expression is to the juncture of group l, and *expression is to the juncture of group y; its condition is that if l or y directly are connected with the nitrogen of x, then l or y are not-nr ar b,-nr cr d,-or e,-s (o) 0-1-c 0-c 3alkyl-aryl ,-s (o) 0-1-c 0-c 3alkyl-heteroaryl aryl ,-s (o) 0-1-c 0-c 3alkyl-aryl-aryl ,-s (o) 0-1-c 0-c 3alkyl-heteroaryl-aryl ,-s (o) 0-1-c 0-c 3alkyl-aryl-heteroaryl or-s (o) 0-1-c 0-c 3alkyl-heteroaryl-heteroaryl, whereineach r awith r bthe nitrogen that is connected with them forms 4 to 7 yuan of heterocyclic radicals with 1 or 2 ring hetero atom together, or have 5 to 8 yuan of bridge joint heterocyclic radicals of 1 or 2 ring hetero atom, described heterocyclic radical is randomly replaced by 1-3 substituting group, and described substituting group is independently selected from h, oh, oxo, n (r c) (r d), c 1-c 6alkyl, aryl, heteroaryl ,-c 1-c 6alkyl-aryl ,-c 1-c 6alkyl-heteroaryl ,-c 1-c 3alkoxy-c 1-c 3alkyl ,-c 2-c 3alkyl-oh ,-c 2-c 3alkyl-o-c 1-c 4alkyl ,-c 5-c 6cycloalkyl ,-c 0-c 3alkyl-n (h)-c (o)-c 1-c 3alkyl ,-c 0-3alkyl-n (h)-c (o)-alkylhalide group ,-c 0-c 3alkyl-nhc (o) o-c 1-c 3alkyl-aryl ,-c 0-c 3alkyl-cf 3,-c 0-c 3alkyl-nhc (o) o-c 1-c 3alkyl-heteroaryl and-c 0-c 3alkyl-nh 2, wherein said heterocyclic radical randomly condenses mutually with aryl or heteroaryl; each r cwith r dbe independently selected from h ,-c 1-c 6alkyl ,-c 2-c 3alkyl-or e, aryl, heteroaryl ,-heteroaryl-heteroaryl ,-heteroaryl-aryl ,-aryl-heteroaryl ,-c (o)-aryl ,-c 1-c 3-alkoxy-c 1-c 3-alkyl ,-c 2-c 3alkyl-o-c 1-c 3alkyl ,-c 2-c 3alkyl-nr er f,-ch 2-c (ch 3) 2-nr er f, wherein each aryl and heteroaryl randomly by one, two or three independently are selected from amino, och 3replace with the substituting group of oh; or r cthe carbon that is connected with them with y forms 4 to the 7 yuan of member ring systems with 0-2 ring hetero atom that are optionally substituted, each r ewith r fbe independently selected from-h ,-alkyl ,-aryl ,-aryl-aryl ,-heteroaryl, heteroaryl-aryl, heteroaryl-heteroaryl ,-c (o)-alkyl and-c (o) cf 3and each r sbe independently selected from-h, c 1-c 6alkyl, aryl, heteroaryl, heterocyclic radical, cycloalkyl and protecting group, wherein each cycloalkyl, heterocyclic radical, aryl, alkyl and heteroaryl moieties randomly are substituted, andwherein the cycloalkyl in l, heterocyclic radical, aryl, alkyl or heteroaryl moieties randomly link to each other with cycloalkyl, heterocyclic radical, aryl, alkyl or heteroaryl among the y by key or by the bridge joint substituting group,its condition isdescribed compound does not have formula (a)whereineach r 10be selected from h, oh ,-ch 2oh, nh 2, cooh and c 1-c 4alkyl; andeach r 11be selected from h, halogen, c 1-c 6alkyl, c 1-c 4alkoxyl group ,-oc (o) c 1-c 4alkyl ,-nh 2,-nh (c 1-c 4alkyl) ,-n (c 1-c 4alkyl) 2,-sh ,-s-c 1-c 4alkyl ,-cooh and-c (o) o-c 1-c 4alkyl; described compound does not have formula (b)whereinr 12be h, alkyl, halogen or alkoxyl group; r 13be hydrogen or c 1-c 5alkyl; and r 14be h or oh; described compound does not have formula (b), wherein r 14be h, r 12be no 2and r 13be h; and described compound is not 10,11-dihydro-5h-dibenzo [a, d] suberene-5-hydroxamic acid.
히스톤 탈아세틸화효소의 억제제본 발명은 히스톤 탈아세틸화효소를 억제하는 화합물에 관한 것이다. 보다 구체적으로, 본 발명은 하기 화학식 (I)의 화합물 및 이의 N-옥사이드, 수화물, 용매화물, 약제학적으로 허용되는 염, 프로드럭 및 복합체, 및 이의 라세믹 및 스케일믹 혼합물, 부분입체이성질체 및 거울상이성질체를 제공한다:  상기 식에서, L, M, X 및 Y 기는 본원에 정의된 바와 같다.하기 화학식 (I)의 화합물 또는 이의 N-옥사이드, 수화물, 용매화물, 약제학적으로 허용되는 염, 프로드럭 또는 복합체, 또는 이의 라세믹 및 스케일믹(scalemic) 혼합물, 부분입체이성질체 또는 거울상이성질체: [이미지] 상기 식에서, M은 알킬, -N(Re)ORs, -CF3, -C(O)N(Re)(Rf), -헤테로아릴, -H, -OH, -C(O)ORe, -CH2-S(아세틸), -CH2-SRe 및 -헤테로시클로알킬로 구성된 군으로부터 선택되고; X는 CH, C(OH), C(C1-C4알킬), C(할로), C(아릴), C(헤테로아릴), C(Rc), [이미지]으로 구성된 군으로부터 선택되고; 여기서 *는 L 기에 부착되는 점을 나타내고 **는 Y 기에 부착되는 점을 나타내며; L 및 Y는 독립적으로 C1-C4알킬, 헤테로알킬, 알케닐, 알키닐, -NRaRb, -NRcRd, -ORe, -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)-, -N(Re)-C(O)-, -C(O)-N(Re)-, -N(Re)-C(O)-N(Rf)-, -N(Re)-C(O)-O-, -O-C(O)-N(Re)-, -O-, -N(Re)-C(O)-C2-C4알킬-O-, -O-C2-C4알킬-N(Re)-, -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, -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-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, -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)2-헤테로시클릴-헤테로아릴, -C0-C3알킬-아릴-헤테로시클릴-C(O)-아릴, -C0-C3알킬-헤테로아릴-헤테로시클릴-C(O)-아릴, -C0-C3알킬-아릴-헤테로시클릴-C(O)-헤테로아릴, -C0-C3알킬-헤테로아릴-헤테로시클릴-C(O)-헤테로아릴, -C0-C3알킬-아릴-C(O)-헤테로시클릴-아릴, -C0-C3알킬-헤테로아릴-C(O)-헤테로시클릴-아릴, -C0-C3알킬-아릴-C(O)-헤테로시클릴-헤테로아릴, -C0-C3알킬-헤테로아릴-C(O)-헤테로시클릴-헤테로아릴, -C0-C3알킬-아릴-헤테로시클릴-C(O)NRe-아릴, -C0-C3알킬-헤테로아릴-헤테로시클릴-C(O)NRe-아릴, -C0-C3알킬-아릴-헤테로시클릴-C(O)NRe-헤테로아릴, -C0-C3알킬-헤테로아릴-헤테로시클릴-C(O)NRe-헤테로아릴, -C0-C3알킬-아릴-NReC(O)-헤테로시클릴-아릴, -C0-C3알킬-헤테로아릴-NReC(O)-헤테로시클릴-아릴, -C0-C3알킬-아릴-NReC(O)-헤테로시클릴-헤테로아릴, -C0-C3알킬-헤테로아릴-NReC(O)-헤테로시클릴-헤테로아릴, -C0-C3알킬-아릴-헤테로시클릴-C(O)O-아릴, -C0-C3알킬-헤테로아릴-헤테로시클릴-C(O)O-아릴, -C0-C3알킬-아릴-헤테로시클릴-C(O)O-헤테로아릴, -C0-C3알킬-헤테로아릴-헤테로시클릴-C(O)O-헤테로아릴, -C0-C3알킬-아릴-OC(O)-헤테로시클릴-아릴, -C0-C3알킬-헤테로아릴-OC(O)-헤테로시클릴-아릴, -C0-C3알킬-아릴-OC(O)-헤테로시클릴-헤테로아릴, 및 -C0-C3알킬-헤테로아릴-OC(O)-헤테로시클릴-헤테로아릴로 구성된 군으로부터 선택되고, 단, L 또는 Y가 X의 질소에 직접 결합될 때, L 또는 Y는 -NRaRb, -NRcRd, -ORe, -S(O)0-1-C0-C3알킬-아릴, -S(O)0-1-C0-C3알킬-헤테로아릴아릴, -S(O)0-1-C0-C3알킬-아릴-아릴, -S(O)0-1-C0-C3알킬-헤테로아릴-아릴, -S(O)0-1-C0-C3알킬-아릴-헤테로아릴 또는 -S(O)0-1-C0-C3알킬-헤테로아릴-헤테로아릴이 아니고, 여기서, 각 Ra 및 Rb는 이들이 결합된 질소와 함께 1 또는 2개의 환상(annular) 헤테로원자를 지니는 4 내지 7원 헤테로시클릴, 또는 1 또는 2개의 환상 헤테로원자를 지니는 5 내지 8원 브릿징된 헤테로시클릴을 형성하고, 헤테로시클릴은 H, OH, 옥소, N(Rc)(Rd), C1-C6알킬, 아릴, 헤테로아릴, -C1-C6알킬-아릴, -C1-C6알킬-헤테로아릴, -C1-C3알콕시-C1-C3알킬, -C2-C3알킬-OH, -C2-C3알킬-O-C1-C4알킬, -C5-C6시클로알킬, -C0-C3알킬-N(H)-C(O)-C1-C3알킬, -C0-3알킬-N(H)-C(O)-할로알킬, -C0-C3알킬-NHC(O)O-C1-C3알킬-아릴, -C0-C3알킬-CF3, -C0-C3알킬-NHC(O)O-C1-C3알킬-헤테로아릴 및 -C0-C3알킬-NH2로 구성된 군으로부터 독립적으로 선택된 1-3개의 치환기로 치환되거나 치환되지 않으며, 여기서 상기 헤테로시클릴은 아릴 또는 헤테로아릴에 융합되거나 융합되지 않고; 각 Rc 및 Rd는 독립적으로 H, -C1-C6알킬, -C2-C3알킬-ORe, 아릴, 헤테로아릴, -헤테로아릴-헤테로아릴, -헤테로아릴-아릴, -아릴-헤테로아릴, -C(O)-아릴, -C1-...