POLYSUBSTITUTED BENZENE COMPOUND AND PREPARATION METHOD AND USE THEREOFThe present invention provides a novel EZH2 inhibitor compound represented by formula (I) and a use of the inhibitor compound in preventing or treating a disease mediated by EZH2. A compound of formula (I): or a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof, wherein: X and Y are each independently selected from a covalent bond, -CH2-, -C(=O)-, -O-, -S-, -S(O)-, -S(O)2-, and -NR9-, wherein R9 is selected from H, C1-C6 alkyl, and C1-C6 haloalkyl; R1 is selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C12 cycloalkyl, 3-12 membered heterocyclyl, 6-10 membered aryl, and 5-6 membered heteroaryl, wherein the C1-C6 alkyl, the C2-C6 alkenyl, the C2-C6 alkynyl, the C3-C12 cycloalkyl, the 3-12 membered heterocyclyl, the 6-10 membered aryl, and the 5-6 membered heteroaryl are optionally substituted with one or more groups selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkyl-S-, C1-C6 alkyl-C(=O)-, C1-C6 alkyl-S(O)-, C1-C6 alkyl-S(O)2-, C1-C6 alkyl-OC(=O)-, C1-C6 alkyl-OS(O)2-, halogen, -CN, -OH, and NR1'R1', wherein R1' and R1' are each independently selected from H, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl, wherein the C1-C6 alkyl, the C2-C6 alkenyl, and the C2-C6 alkynyl are optionally substituted with one or more groups selected from C1-C6 alkoxy, halogen, -OH, -CN, -SH, and NH2; R2, R3, and R10 are each independently selected from H, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, halogen, and -CN; R4 is C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl is optionally substituted with -Q-T, wherein Q is selected from covalent bond, -CH2-, -C(=O)-, -O-, -S-, -S(O)-, -S(O)2-, and -NR9'-, wherein R9' is selected from H, C1-C6 alkyl, and C1-C6 haloalkyl, and T is selected from H, halogen, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C12 cycloalkyl, 3-12 membered heterocyclyl, 6-10 membered aryl, and 5-6 membered heteroaryl, wherein the C1-C6 alkyl, the C2-C6 alkenyl, the C2-C6 alkynyl, the C3-C12 cycloalkyl, the 3-12 membered heterocyclyl, the 6-10 membered aryl, and the 5-6 membered heteroaryl are optionally substituted with one or more groups selected from -OH, -SH, -NH2, halogen, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkyl-S-, C1-C6 alkyl-NH-, (C1-C6 alkyl)2N-, C1-C6 alkyl-C(=O)-, C1-C6 alkyl-S(O)-, C1-C6 alkyl-S(O)2-, C1-C6 alkyl-OC(=O)-, and C1-C6 alkyl-OS(O)2-; R5 is selected from H and C1-C6 alkyl; and R6, R7, and R8 are each independently selected from H, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkyl-S-, C1-C6 alkyl-NH-, (C1-C6 alkyl)2N-, C1-C6 alkyl-C(=O)-, C1-C6 alkyl-S(O)-, C1-C6 alkyl-S(O)2-, C1-C6 alkyl-OC(=O)-, and C1-C6 alkyl-OS(O)2-, wherein the C1-C6 alkyl, the C2-C6 alkenyl, the C2-C6 alkynyl, the C1-C6 alkoxy, the C1-C6 alkyl-S-, the C1-C6 alkyl-NH-, the (C1-C6 alkyl)2N-, the C1-C6 alkyl-C(=O)-, the C1-C6 alkyl-S(O)-, the C1-C6 alkyl-S(O)2-, the C1-C6 alkyl-OC(=O)-, and the C1-C6 alkyl-OS(O)2 are optionally substituted with one or more groups selected from -OH, -SH, -NH2, halogen, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkyl-S-, C1-C6 alkyl-NH-, (C1-C6 alkyl)2N-, C1-C6 alkyl-C(=O)-, C1-C6 alkyl-S(O)-, C1-C6 alkyl-S(O)2-, C1-C6 alkyl-OC(=O)-, and C1-C6 alkyl-OS(O)2-.
다치환 벤젠화합물 및 이의 제조방법본 화합물은 식 (I)로 나타나는 신규 EZH2 저해제 화합물과, EZH2 매개 질병의 예방 또는 치료에서의 해당 저해제 화합물의 용도에 관한다.(I)식 (I)의 화합물:(I),또는 이의 입체이성질체, 이의 호변이성질체 및 약학적으로 허용 가능한 염에 있어서,X 및 Y는 공유결합, -CH2-, -C(=O)-, -O-, -S-, -S(O)-, -S(O)2-, -NR9-로부터 각각 독립적으로 선택되고, R9는 H, C1-C6 알킬, C1-C6 할로알킬로부터 선택되며;R1은 C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, C3-C12 시클로알킬, 3~12원 헤테로시클릴, 6~10원 아릴, 5~6원 헤테로아릴로부터 선택되고, 상기한 C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, C3-C12 시클로알킬, 3~12원 헤테로시클릴, 6~10원 아릴, 5~6원 헤테로아릴은, C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, C1-C6 할로알킬, C1-C6 알콕시, C1-C6 알킬-S-, C1-C6 알킬-C(=O)-, C1-C6 알킬-S(O)-, C1-C6 알킬-S(O)2-, C1-C6 알킬-OC(=O)-, C1-C6 알킬-OS(O)2-, 할로겐, -CN, -OH, NR1'R1"로부터 선택된 1종 이상의 기로 치환되어도 좋고, R1' 및 R1"은 H, C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐로부터 각각 독립적으로 선택되고, 상기한 C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐은 C1-C6 알콕시, 할로겐, -OH, -CN, -SH, NH2로부터 선택된 1종 이상의 기로 치환되어도 좋으며;R2, R3, R10은 H, 히드록시, C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, C1-C6 알콕시, 할로겐, -CN으로부터 각각 독립적으로 선택되고;R4는 C3-C6 시클로알킬이며, C3-C6 시클로알킬은 -Q-T로 치환되어도 좋고, Q는 공유결합, -CH2-, -C(=O)-, -O-, -S-, -S(O)-, -S(O)2-, -NR9'-로부터 선택되며, R9'는 H, C1-C6 알킬, C1-C6 할로알킬로부터 선택되고, T는 H, 할로겐, -CN, C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, C3-C12 시클로알킬, 3~12원 헤테로시클릴, 6~10원 아릴, 5~6원 헤테로아릴로부터 선택되고, 상기한 C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, C3-C12 시클로알킬, 3~12원 헤테로시클릴, 6~10원 아릴, 5~6원 헤테로아릴은 -OH, -SH, -NH2, 할로겐, -CN, C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, C1-C6 알콕시, C1-C6 알킬-S-, C1-C6 알킬-NH-, (C1-C6 알킬)2N-, C1-C6 알킬-C(=O)-, C1-C6 알킬-S(O)-, C1-C6 알킬-S(O)2-, C1-C6 알킬-OC(=O)-, C1-C6 알킬-OS(O)2-로부터 선택된 1종 이상의 기로 치환되어도 좋고;R5는 H 및 C1-C6 알킬로부터 선택되고; 및R6, R7, R8은 H, 히드록시, C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, C1-C6 알콕시, C1-C6 알킬-S-, C1-C6 알킬-NH-, (C1-C6 알킬)2N-, C1-C6 알킬-C(=O)-, C1-C6 알킬-S(O)-, C1-C6 알킬-S(O)2-, C1-C6 알킬-OC(=O)-, C1-C6 알킬-OS(O)2-로부터 각각 독립적으로 선택되고, 상기한 C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, C1-C6 알콕시, C1-C6 알킬-S-, C1-C6 알킬-NH-, (C1-C6 알킬)2N-, C1-C6 알킬-C(=O)-, C1-C6 알킬-S(O)-, C1-C6 알킬-S(O)2-, C1-C6 알킬-OC(=O)-, C1-C6 알킬-OS(O)2는 -OH, -SH, -NH2, 할로겐, -CN, C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, C1-C6 알콕시, C1-C6 알킬-S-, C1-C6 알킬-NH-, (C1-C6 알킬)2N-, C1-C6 알킬-C(=O)-, C1-C6 알킬-S(O)-, C1-C6 알킬-S(O)2-, C1-C6 알킬-OC(=O)-, C1-C6 알킬-OS(O)2-로부터 선택된 1종 이상의 기로 치환되어도 좋은, 화합물.