Benzyl substituted indazoles as bub1 inhibitorsCompounds of formula (I) as defined herein and their use as pharmaceuticals.The compound of formula (i)whereinv, w, y and z represent ch or cr independently of one another2, one wherein in v, w, y and z represents cr2or,v represents n, and w, y and z represent ch or cr independently of one another2,or,v and y represent n, and w and z represent ch or cr independently of one another2,r1represent and be selected from following group：c1-c6- alkyl, c1-c6- haloalkyl, c3-c6- cycloalkyl, (c1-c3- alkoxy)-(c2-c3- alkyl)-and (c3-c6- cycloalkyl)-(c1-c3- alkyl)-,r2halogen is represented independently of one another or selected from following group：c1-c3- alkyl, c3-c4- cycloalkyl, c1-c3- haloalkyl, c1-c3- alkoxy, c1-c3- halogenated alkoxy ,-n (h) c (= o)-(c1-c3- alkyl) ,-n (h) c (=o) h ,-n (h) c (=o)-(c1-c3- hydroxy alkyl) ,-n (h) c (=o)-(c1-c3- alkane base)-(c1-c3- alkoxy) ,-n (h) c (=o)-phenyl ,-n (h) c (=o)-(c3-c4- cycloalkyl) ,-n (h) c (=o)-(c1-c3- alkyl)-(c3-c4- cycloalkyl) and-(h) c (=o) n (h) r8,- n (h) c (=the o)-phenyl is optionally substituted once, twice or thrice by identical or different substituent in phenyl ring, described substituent is selected from：halogen, hydroxyl, cyano group, c1-c4- alkyl, c1-c4- haloalkyl, c1-c4- alkoxy, c1-c4- halogenated alkoxy, c3-c4- cycloalkyl and c3-c4- cycloalkyl oxy,- n (h) c (=o)-(c3-c4- cycloalkyl) in c3-c4it is optionally substituted that-cycloalkyl ring is selected from following substituent：fluorine, chlorine, trifluoromethyl and methoxyl group,r3represent and be selected from following group：c2-c6- hydroxy alkyl and r4,the c2-c6it is optionally substituted that-hydroxy alkyl is selected from following one, two or three halogen atom：fluorine and chlorine,r4representative-(c2-c6- alkyl)-oc (=o)-c (h) (r5)-n(h)c(=o)-c(h)(r7)-nh2,wherein c2-c6it is optionally substituted that-alkyl is selected from following one, two or three halogen atom：fluorine and chlorine,r5and r7hydrogen (glycine) is represented independently of one another or selected from following group：-ch3(alanine) ,-c (h) (ch3)2(valine) ,-(ch2)2ch3(norvaline) ,-ch2c(h)(ch3)2it is (bright propylhomoserin) ,-c (h) (ch3)ch2ch3(isoleucine) ,-(ch2)3ch3(nor-leucine) ,-c (ch3)3(the sweet ammonia of the 2- tert-butyl groups acid), benzyl (phenylalanine), 4- hydroxybenzyls (tyrosine) ,-(ch2)3nh2(ornithine) ,-(ch2)4nh2(rely ammonia acid) ,-(ch2)2c(h)(oh)ch2nh2(hydroxylysine) ,-ch2oh (serine) ,-(ch2)2oh (homoserine) ,-c (h) (oh)ch3(threonine) ,-(ch2)3n(h)c(=nh)nh2(arginine) ,-(ch2)3n(h)c(=o)nh2(citrulling) ,- ch2c(=o)nh2(asparagine) ,-ch2c (=o) oh (aspartic acid) ,-(ch2)2c (=o) oh (glutamic acid) ,-(ch2)2c (=o)nh2(glutamine) ,-ch2sh (cysteine) ,-(ch2)2sh (homocysteine) ,-(ch2)2sch3(first sulphur ammonia acid) ,-ch2sch3(s- methyl cysteines), (1h- imidazol-4 yl) methyl-(histidine), (1h- indol-3-yl) methyl- (tryptophan) ,-ch2nh2(2,3- diaminopropionic acids) and-(ch2)2nh2(2,4-diamino-butanoic),r8represent hydrogen or selected from following group：c1-c3- alkyl, c1-c3- haloalkyl, c2-c3- hydroxy alkyl, c3-c4- cycloalkyl, (c3-c4- cycloalkyl)-(c1-c3- alkyl)-and (c1-c3- alkoxy)-(c2-c3- alkyl)-,or n- oxides, salt, dynamic isomer or the stereoisomer of the compound, or the n- oxides, tautomerism the salt of body or stereoisomer.
Bub1 억제제로서의 벤질 치환된 인다졸본원에 정의된 바와 같은 화학식 (I)의 화합물 및 약제로서의 그의 용도가 개시된다:화학식 (I)의 화합물, 또는 상기 화합물의 N-옥사이드, 염, 호변이성체 또는 입체이성체, 또는 상기 N-옥사이드, 호변이성체 또는 입체이성체의 염:[이미지]상기 식에서,V, W, Y 및 Z는 서로 독립적으로 CH 또는 CR2를 나타내고, 여기서 V, W, Y 및 Z 중 하나는 CR2를 나타내거나, 또는V는 N을 나타내고, W, Y 및 Z는 서로 독립적으로 CH 또는 CR2를 나타내거나, 또는V 및 Y는 N을 나타내고, W 및 Z는 서로 독립적으로 CH 또는 CR2를 나타내며,R1은 C1-C6-알킬, C1-C6-할로알킬, C3-C6-사이클로알킬, (C1-C3-알콕시)-(C2-C3-알킬)-, 및 (C3-C6-사이클로알킬)-(C1-C3-알킬)- 중에서 선택되는 기를 나타내고,R2는 서로 독립적으로 할로겐, 또는 C1-C3-알킬, C3-C4-사이클로알킬, C1-C3-할로알킬, C1-C3-알콕시, C1-C3-할로알콕시, -N(H)C(=O)-(C1-C3-알킬), -N(H)C(=O)H, -N(H)C(=O)-(C1-C3-하이드록시알킬), -N(H)C(=O)-(C1-C3-알킬)-(C1-C3-알콕시), -N(H)C(=O)-페닐, -N(H)C(=O)-(C3-C4-사이클로알킬), -N(H)C(=O)-(C1-C3-알킬)-(C3-C4-사이클로알킬), 및 -N(H)C(=O)N(H)R8 중에서 선택되는 기를 나타내고, 상기 -N(H)C(=O)-페닐은 페닐 고리에서 할로겐, 하이드록시, 시아노, C1-C4-알킬, C1-C4-할로알킬, C1-C4-알콕시, C1-C4-할로알콕시, C3-C4-사이클로알킬, 및 C3-C4-사이클로알킬옥시 중에서 선택되는 치환체에 의해 동일하거나 상이하게 1, 2 또는 3회 임의로 치환되고, 상기 -N(H)C(=O)-(C3-C4-사이클로알킬)은 C3-C4-사이클로알킬 고리에서 불소, 염소, 트리플루오로메틸, 및 메톡시 중에서 선택되는 치환체에 의해 임의로 치환되고, R3은 C2-C6-하이드록시알킬, 및 R4 중에서 선택되는 기를 나타내고, 상기 C2-C6-하이드록시알킬기는 불소, 및 염소 중에서 선택되는 1, 2 또는 3개의 할로겐 원자에 의해 임의로 치환되고,R4는 -(C2-C6-알킬)-OC(=O)-C(H)(R5)-N(H)C(=O)-C(H)(R7)-NH2를 나타내고, 여기서 C2-C6-알킬은 불소, 및 염소 중에서 선택되는 1, 2 또는 3개의 할로겐 원자에 의해 임의로 치환되고,R5 및 R7은 서로 독립적으로 수소 (글라이신), 또는 -CH3 (알라닌), -C(H)(CH3)2 (발린), -(CH2)2CH3 (노르발린), -CH2C(H)(CH3)2 (류신), -C(H)(CH3)CH2CH3 (이소류신), -(CH2)3CH3 (노르류신), -C(CH3)3 (2-tert-부틸글라이신), 벤질 (페닐알라닌), 4-하이드록시벤질 (티로신), -(CH2)3NH2 (오르니틴), -(CH2)4NH2 (라이신), -(CH2)2C(H)(OH)CH2NH2 (하이드록시라이신), -CH2OH (세린), -(CH2)2OH (호모세린), -C(H)(OH)CH3 (트레오닌), -(CH2)3N(H)C(=NH)NH2 (아르기닌), -(CH2)3N(H)C(=O)NH2 (시트룰린), -CH2C(=O)NH2 (아스파라긴), -CH2C(=O)OH (아스파르트산), -(CH2)2C(=O)OH (글루탐산), -(CH2)2C(=O)NH2 (글루타민), -CH2SH (시스테인), -(CH2)2SH (호모시스테인), -(CH2)2SCH3 (메티오닌), -CH2SCH3 (S-메틸시스테인), (1H-이미다졸-4-일)메틸- (히스티딘), (1H-인돌-3-일)메틸- (트립토판), -CH2NH2 (2,3-디아미노프로판산), 및 -(CH2)2NH2 (2,4-디아미노부탄산) 중에서 선택되는 기를 나타내고, R8은 수소, 또는 C1-C3-알킬, C1-C3-할로알킬, C2-C3-하이드록시알킬, C3-C4-사이클로알킬, (C3-C4-사이클로알킬)-(C1-C3-알킬)-, 및 (C1-C3-알콕시)-(C2-C3-알킬)- 중에서 선택되는 기를 나타낸다.