BENZIMIDAZOLE AND AZABENZIMIDAZOLE COMPOUNDS THAT INHIBIT ANAPLASTIC LYMPHOMA KINASECompounds of Formula (I) are useful inhibitors of anaplastic lymphoma kinase. Compounds of Formula (I) have the following structure: where the definitions of the variables are provided herein.A compound or a pharmaceutically acceptable salt thereof, tautomer thereof, a pharmaceutically acceptable salt of the tautomer, a stereoisomer of any of the foregoing, or a mixture thereof,wherein:R1 is -H;R2 is -H;R3 is selected from -H, -F, -CI, -Br, -I; -(C C6)alkyl, -(C2-C6)alkenyl, -(C2- C6)alkynyl, -CF3, -OH, -OCF3, -0-(Ci-C6)alkyl, -OCHF2, -SH, -S-(C C6)alkyl, -NH2, -N(H)-(C C6)alkyl, -N((Ci-C6)alkyl)2, -N02, -C≡N, -C(=0)OH, -C(=0)0-(C C6)alkyl, C6)alkyl, -N((Ci-C6)alkyl)-C(=0)-(Ci-C6)alkyl, -(Ci-C4)alkylene-OH, -(Q- C4)alkylene-NH2, -(Ci-C4)alkylene-N(H)-(Ci-C6)alkyl, -(Ci-C4)alkylene-N((Ci- C6)alkyl)2, or phenyl optionally substituted with 1 , 2, or 3 substituents selected from -F, -CI, -Br, -I; -(Ci-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -CF3, -OH, -OCF3, -0-(Ci- C6)alkyl, -OCHF2, -SH, -S-(Ci-C6)alkyl, -NH2, -N(H)-(Ci-C6)alkyl, -N((Ci-C6)alkyl)2, -NO2, -C≡N, -C(=0)OH, or -C(=0)N((C1-C6)alkyl)2;X is selected from CR4 or N;R4 is absent if X is N, or is selected from -H, -F, -CI, -Br, -I; -(Ci-C6)alkyl, -(C2- C6)alkenyl, -(C2-C6)alkynyl, -CF3, -OH, -OCF3, -0-(Ci-C6)alkyl, -OCHF2, -SH, -S-(C C6)alkyl, -NH2, -N(H)-(Ci-C6)alkyl, -N((Ci-C6)alkyl)2, -N02, -C≡N, -C(=0)OH, -(Ci-C4)alkylene-OH, -(Ci-C4)alkylene-NH2, -(Ci-C4)alkylene-N(H)-(Ci-C6)alkyl, or - (Ci-C4)alkylene-N((Ci-C6)alkyl)2;Y is selected from a C3-C12 cycloalkyl or a 3-10 membered heterocyclyl comprising 1, 2, or 3 heteroatoms selected from O, S, or N; wherein the C3-C12 cycloalkyl and the 3-10 membered heterocyclyl may be monocyclic, bicyclic, or tricyclic, and further wherein the C3-Q2 cycloalkyl and the 3-10 membered heterocyclyl are unsubstituted or are optionally substituted with 1, 2, or 3 substituents independently selected from -Y', -F, -CI, -Br, -I, -C≡N, -N02, -OH, -0-(C C6)alkyl, -SH, -S-(C C6)alkyl, -OCF3, -OCHF2, -CF3, -(Ci-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -NH2, -NH((Ci-C4)alkyl), -N((Ci-C4)alkyl)2, -NHS02-(Ci-C6)alkyl, -NHC(=0)-(C C6)alkyl, C4)alkylene-F, -C(=0)NH-(C2-C4)alkenyl, -C(=0)NH-OH C4)alkylene-F, -C(=0)-(C2-C4)alkenyl, C4)alkylene-NH((Ci-C4)alkyl), -C(=0)-(Ci-C4)alkylene-N((Ci-C4)alkyl)2,-C(=0)NH-(Ci-C4)alkylene-OH, -C(=0)NH-(Ci-C4)alkylene-0-(Ci-C6)alkyl,-C(=0)NH-(Ci-C4)alkylene-Y', C6)alkyl, -C(=0)NH-(Ci-C4)alkylene-NH2, -C(=0)NH-(Ci-C4)alkylene-NH((Ci- C6)alkyl), -C(=0)NH-(Ci-C4)alkylene-N((Ci-C6)alkyl)2, -S02NH2, -S02NH((CC6)alkyl), -S02N((Ci-C6)alkyl)2, -S02NH((C2-C4)alkenyl), -S02NH((C2-C4)alkynyl), -S02NH-Y', -S02NH-(Ci-C4)alkylene-OH, -S02NH-(Ci-C4)alkylene-0-(Ci-C4)alkyl, -S02-(Ci-C6)alkyl, -S02-Y', -SO-(Ci-C6)alkyl, -(Ci-C4)alkylene-NH-C(=0)-(Ci-C6)alkyl, -(Ci-C4)alkylene-NH-(Ci-C6)alkyl, -(Ci-C4)alkylene-N((Ci-C6)alkyl)2 -(CC4)alkylene-OH, -(Ci-C4)alkylene-0-(Ci-C6)alkyl, -(Ci-C4)alkylene-C(=0)-(Ci-C6)alkyl, -(Ci-C4)alkylene-C(=0)-0-(Ci-C6)alkyl, or -(Ci-C4)alkylene-C(=0)-OH; wherein two substituents on a carbon ring member of the Y cycloalkyl or heterocyclyl may join to form a 3-7 membered cycloalkyl group or a 3-7 membered heterocyclyl group that comprises 1 to 3 heteroatoms selected from N, O, or S; and further wherein 1 or 2 carbon atom ring members of the 3-7 membered cycloalkyl or the 3-7 membered heterocyclyl group formed from the two substituents on the carbon ring member of the Y cycloalkyl or heterocyclyl may be double bonded to an O atom;Y' may be absent or is a C6-C10 aryl, a 5-10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from O, S, or N, or a 3-7 membered heterocyclyl comprising 1, 2, or 3 heteroatoms selected from O, S, or N, wherein the C6- Cio aryl, the 5-10 membered heteroaryl, or the 3-7 membered heterocyclyl Y' groups are unsubstituted or are optionally substituted with 1, 2, or 3 substituents independently selected from -F, -CI, -Br, -I, -C≡N, -N02, -(C C6)alkyl, -(C2-C6)alkenyl, -(C2- C6)alkynyl, -(Ci-C4)alkylene-OH, -NH2, -NH((Ci-C4)alkyl), -N((C C4)alkyl)2, -C(=0)NH2, -S02NH2, -S02NH((Ci- C4)alkyl), -S02N((C C4)alkyl)2, -NHS02-(Ci-C4)alkyl, -S02-(Ci-C6)alkyl, -SO-(Ci-C4)alkyl, -(Ci-C4)alkylene-NH-C(=0)-(Ci-C4)alkyl, -CF3, -C02H, -C(=0)-0-(Ci-C4)alkyl,-C(=0)NH-(Ci-C4)alkylene-NH((Ci-C4)alkyl), -C(=0)NH-(Ci-C4)alkylene-N((Ci- C4)alkyl)2, -C(=0)NH-(Ci-C4)alkylene-OH, -C(=0)NH-(Ci-C4)alkylene-0-(Ci-C4)alkyl, -(Ci-C4)alkylene-C(=0)-(Ci-C4)alkyl, -(C C4)alkylene-C(=0)-0-(Ci-C4)alkyl, -(Ci-C4)alkylene-C(=0)-OH, -OH, -0-(Ci-C6)alkyl, -SH, -S-(Ci-C6)alkyl, -OCF3, or -OCHF2;Y' may be absent or is selected from a C3-C10 cycloalkyl; a 3-10 membered heterocyclyl comprising 1, 2, or 3 heteroatoms selected from N, O, and S; a C6-Ci0 aryl; or a 5-10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S; wherein the C3-C10 cycloalkyl and the 3-10 membered heterocyclyl may be monocyclic or bicyclic, and further wherein the C3-C10 cycloalkyl, the 3-10 membered heterocyclyl, the C6-C10 aryl, or the 5-10 membered heteroaryl Y' groups are unsubstituted or are optionally substituted with 1 , 2, or 3 substituents...
역형성 림프종 키나제를 억제하는 벤즈이미다졸 및 아자벤즈이미다졸 화합물화학식 I의 화합물은 역형성 림프종 키나제의 유용한 억제제이다. 화학식 I의 화합물은 다음의 구조를 갖는다: 화학식 I 위의 화학식 I에서, 변수들의 정의는 본원에 제공되어 있다.화학식 I의 화합물, 또는 이의 약제학적으로 허용되는 염, 이의 토토머, 상기 토토머의 약제학적으로 허용되는 염, 상기한 것들 중의 어느 것의 입체이성체, 또는 이들의 혼합물.화학식 I위의 화학식 I에서, R1은 -H이고; R2는 -H이고;R3은 -H, -F, -Cl, -Br, -I; -F, -Cl, -Br, -I로부터 선택된 1, 2 또는 3개의 치환체로 임의로 치환된, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -CF3, -OH, -OCF3, -O-(C1-C6)알킬, -OCHF2, -SH, -S-(C1-C6)알킬, -NH2, -N(H)-(C1-C6)알킬, -N((C1-C6)알킬)2, -NO2, -C≡N, -C(=O)OH, -C(=O)O-(C1-C6)알킬, -C(=O)NH2, -C(=O)N(H)-(C1-C6)알킬, -C(=O)N((C1-C6)알킬)2, -N(H)-C(=O)-(C1-C6)알킬, -N((C1-C6)알킬)-C(=O)-(C1-C6)알킬, -(C1-C4)알킬렌-OH, -(C1-C4)알킬렌-NH2, -(C1-C4)알킬렌-N(H)-(C1-C6)알킬, -(C1-C4)알킬렌-N((C1-C6)알킬)2 또는 페닐; -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -CF3, -OH, -OCF3, -O-(C1-C6)알킬, -OCHF2, -SH, -S-(C1-C6)알킬, -NH2, -N(H)-(C1-C6)알킬, -N((C1-C6)알킬)2, -NO2, -C≡N, -C(=O)OH, -C(=O)O-(C1-C6)알킬, -C(=O)NH2, -C(=O)N(H)-(C1-C6)알킬 또는 -C(=O)N((C1-C6)알킬)2로부터 선택되고;X는 CR4 또는 N으로부터 선택되고;R4는, 부재하거나(X가 N인 경우), -H, -F, -Cl, -Br, -I; -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -CF3, -OH, -OCF3, -O-(C1-C6)알킬, -OCHF2, -SH, -S-(C1-C6)알킬, -NH2, -N(H)-(C1-C6)알킬, -N((C1-C6)알킬)2, -NO2, -C≡N, -C(=O)OH, -C(=O)O-(C1-C6)알킬, -C(=O)NH2, -C(=O)N(H)-(C1-C6)알킬, -C(=O)N((C1-C6)알킬)2, -(C1-C4)알킬렌-OH, -(C1-C4)알킬렌-NH2, -(C1-C4)알킬렌-N(H)-(C1-C6)알킬 또는 -(C1-C4)알킬렌-N((C1-C6)알킬)2로부터 선택되고;Y는 C3-C12 사이클로알킬, 또는 O, S 또는 N으로부터 선택된 1, 2 또는 3개의 헤테로원자를 포함하는 3원 내지 10원 헤테로사이클릴로부터 선택되고; 여기서, 상기 C3-C12 사이클로알킬 및 상기 3원 내지 10원 헤테로사이클릴은 모노사이클릭, 바이사이클릭 또는 트리사이클릭일 수 있고, 추가로 상기 C3-C12 사이클로알킬 및 상기 3원 내지 10원 헤테로사이클릴은 치환되지 않거나, -Y', -F, -Cl, -Br, -I, -C≡N, -NO2, -OH, -O-(C1-C6)알킬, -SH, -S-(C1-C6)알킬, -OCF3, -OCHF2, -CF3, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -NH2, -NH((C1-C4)알킬), -N((C1-C4)알킬)2, -NHSO2-(C1-C6)알킬, -NHC(=O)-(C1-C6)알킬, -C(=O)NH2, -C(=O)NH((C1-C6)알킬), -C(=O)NH-(C1-C4)알킬렌-CF3, -C(=O)NH-(C1-C4)알킬렌-F, -C(=O)NH-(C2-C4)알케닐, -C(=O)N((C1-C6)알킬)2, -C(=O)NH-OH, -C(=O)NH-O-(C1-C6)알킬, -C(=O)NH-Y", -C(=O)-(C1-C4)알킬렌-CF3, -C(=O)N-(C1-C4)알킬렌-F, -C(=O)-(C2-C4)알케닐, -C(=O)-(C1-C4)알킬렌-NH2, -C(=O)-(C1-C4)알킬렌-NH((C1-C4)알킬), -C(=O)-(C1-C4)알킬렌-N((C1-C4)알킬)2, -C(=O)NH-(C1-C4)알킬렌-OH, -C(=O)NH-(C1-C4)알킬렌-O-(C1-C6)알킬, -C(=O)NH-(C1-C4)알킬렌-Y", -C(=O)-(C1-C6)알킬, -C(=O)-Y", -CO2H, -C(=O)-O-(C1-C6)알킬, -C(=O)NH-(C1-C4)알킬렌-NH2, -C(=O)NH-(C1-C4)알킬렌-NH((C1-C6)알킬), -C(=O)NH-(C1-C4)알킬렌-N((C1-C6)알킬)2, -SO2NH2, -SO2NH((C1-C6)알킬), -SO2N((C1-C6)알킬)2, -SO2NH((C2-C4)알케닐), -SO2NH((C2-C4)알키닐), -SO2NH-Y", -SO2NH-(C1-C4)알킬렌-OH, -SO2NH-(C1-C4)알킬렌-O-(C1-C4)알킬, -SO2-(C1-C6)알킬, -SO2-Y", -SO-(C1-C6)알킬, -(C1-C4)알킬렌-NH-C(=O)-(C1-C6)알킬, -(C1-C4)알킬렌-NH-(C1-C6)알킬, -(C1-C4)알킬렌-N((C1-C6)알킬)2-(C1-C4)알킬렌-OH, -(C1-C4)알킬렌-O-(C1-C6)알킬, -(C1-C4)알킬렌-C(=O)-(C1-C6)알킬, -(C1-C4)알킬렌-C(=O)-O-(C1-C6)알킬 또는 -(C1-C4)알킬렌-C(=O)-OH로부터 독립적으로 선택된 1, 2 또는 3개의 치환체로 임의로 치환되고; 여기서, 상기 Y 사이클로알킬 또는 헤테로사이클릴의 탄소 환 구성원 상의 2개의 치환체는 결합하여 3원 내지 7원 사이클로알킬 그룹을, 또는 N, O 또는 S로부터 선택된 1 내지 3개의 헤테로원자를 포함하는 3원 내지 7원 헤테로사이클릴 그룹을 형성할 수 있고; 추가로 상기 Y 사이클로알킬 또는 헤테로사이클릴의 탄소 환 구성원 상의 2개의 치환체로부터 형성된 상기 3원 내지 7원 사이클로알킬 또는 3원 내지 7원 헤테로사이클릴 그룹의 1 또는 2개의 탄소 원자 환 구성원은 O 원자에 이중 결합될 수 있고; Y'는 부재할 수 있거나, C6-C10 아릴, O, S 또는 N으로부터 독립적으로 선택된 1, 2, 3 또는 4개의 헤테로원자를 포함하는 5원 내지 10원 헤테로아릴, 또는 O, S 또는 N으로부터 선택된 1, 2 또는 3개의 헤테로원자를 포함하는 3원 내지 7원 헤테로사이클릴이고, 여기서, 상기 C6-C10 아릴, 상기 5원 내지 10원 헤테로아릴 또는 상기 3원 내지 7원 헤테로사이클릴 Y' 그룹은 치환되지 않거나, -F, -Cl, -Br, -I, -C≡N, -NO2, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -(C1-C4)알킬렌-OH, -NH2, -NH((C1-C4)알킬), -N((C1-C4)알킬)2, -C(=O)NH2, -C(=O)NH((C1-C4)알킬), -C(=O)N((C1-C4)알킬)2, -SO2NH2, -SO2NH((C1-C4)알킬), -SO2N((C1-C4)알킬)2, -NHSO2-(C1-C4)알킬, -NHC(=O)-(C1-C4)알킬, -SO2-(C1-C6)알킬, -SO-(C1-C4)알킬, -(C1-C4)알킬렌-NH-C(=O)-(C1-C4)알킬, -CF3, -C(=O)-(C1-C4)알킬, -CO2H, -C(=O)-O-(C1-C4)알킬, -C(=O)NH-(C1-C4)알킬렌-NH2, -C(=O)NH-(C1-C4)알킬렌-NH((C1-C4)알킬), -C(=O)NH-(C1-C4)알킬렌-N((C1-C4)알킬)2, -C(=O)NH-(C1-C4)알킬렌-OH, -C(=O)NH-(C1-C4)알킬렌-CF3, -C(=O)NH-(C1-C4)알킬렌-O-(C1-C4)알킬, -(C1-C4)알킬렌-C(=O)-(C1-C4)알킬, -(C1-C4)알킬렌-C(=O)-O-(C1-C4)알킬, -(C1-C4)알킬렌-C(=O)-OH, -OH, -O-(C1-C6)알킬, -SH, -S-(C1-C6)알킬, -OCF3 또는 -OCHF2로부터 독립적으로 선택된 1, 2 또는 3개의 치환체로 임의로 치환되고; Y"는 부재할 수 있거나, C3-C10 사이클로알킬; N, O 및 S로부터 선택된 1, 2 또는 3개의 헤테로원자를 포함하는 3원 내지 10원 헤테로사이클릴; C6-C10 아릴; 또는 N, O 또는 S로부터 독립적으로 선택된 1, 2, 3 또는 4개의 헤테로원자를 포함하는 5원 내지 10원 헤테로아릴로부터 선택되고; 여기서, 상기 C3-C10 사이클로알킬 및 상기 3원 내지 10원 헤테로사이클릴은 모노사이클릭 또는 바이사이클릭일 수 있고, 추가로 상기 C3-C10 사이클로알킬, 상기 3원 내지 10원 헤테로사이클릴, 상기 C6-C10 아릴 또는 상기 5원 내지 10원 헤테로아릴 Y" 그룹은 치환되지 않거나, -F, -Cl, -Br, -I, -C≡N, -NO2, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -(C1-C4)알킬렌-OH, -NH2, -NH((C1-C4)알킬), -N((C1-C4)알킬)2, -C(=O)NH2, -C(=O)NH((C1-C4)알킬), -C(=O)N((C1-C4)알킬)2, -SO2NH2, -SO2NH((C1-C4)알킬), -SO2N((C1-C4)알킬)2, -NHSO2-(C1-C4)알킬, -NHC(=O)-(C1-C4)알킬, -SO2-(C1-C6)알킬, -SO-(C1-C4)알킬, -(C1-C4)알킬렌-NH-C(=O)-(C1-C4)알킬, -CF3, -C(=O)-(C1-C4)알킬, -CO2H, -C(=O)-O-(C1-C4)알킬, -C(=O)NH-(C1-C4)알킬렌-NH2, -C(=O)NH-(C1-C4)알킬렌-NH((C1-C4)알킬), -C(=O)NH-(C1-C4)알킬렌-N((C1-C4)알킬)2, -C(=O)NH-(C1-C4)알킬렌-OH, -C(=O)NH-(C1-C4)알킬렌-CF3, -C(=O)NH-(C1-C4)알킬렌-O-(C1-C4)알킬, -(C1-C4)알킬렌-C(=O)-(C1-C4)알킬, -(C1-C4)알킬렌-C(=O)-O-(C1-C4)알킬, -(C1-C4)알킬렌-C(=O)-OH, -OH, -O-(C1-C6)알킬, -SH, -S-(C1-C6)알킬, -OCF3 또는 -OCHF2로부터 독립적으로 선택된 1, 2 또는 3개의 치환체로 임의로 치환되고; W는 -H, -F, -Cl, -Br, -I, -(C1-C...