VIRAL POLYMERASE INHIBITORSThe present invention relates to viral polymerase inhibitors of formula (I), salts, N-oxides, solvates, hydrates, racemates, enantiomers or isomers thereof, processes for their preparation and their use in the treatment of Flaviviridae viral infections such as Hepatitis C virus (HCV) infections: (I)A compound of formula (I), salts, W-oxides, solvates, hydrates, racemates, enantiomers or isomers thereof:(I )Zi and Z2 are each independently selected from C-H, C-halo, C-C1.4alkyl, C-C1.4alkylhalo, C- Ci_4alkoxy, C-C1.4alkoxyhalo and N;Ri is selected from H, C -6alkyl, C2.6alkenyl, C2-6alkynyl, d ealkoxy, halo,Ci_ alkylhalo, C1. alkoxyhalo, C3.7cycloalkyl, C3.7cycloalkenyl,5-6-membered heterocyclyl and 5-6 membered heteroaryl and wherein alkyl, alkenyl, alkynyl, alkoxy, cycloalkyi, heterocyclyl and heteroaryl in each occurrence may be optionally substituted;R2 is selected from halo, C1-6alkyl, C2.6alkenyl, N02, N(R5)2, NR5R6, NR6(S02R5), S02N(R8)2, SR8, C(R5)2S02R8, NR5C(=0)R8, optionally substituted aryl, optionally substituted aryl-R7, optionally substituted heterocyclyl, optionally substituted heterocyclyl-R7, optionally substituted heteroaryl and optionally substituted heteroaryl-R7;R3 is selected from aryl, aryl-X-aryl, aryl-X-heteroaryl, heteroaryl, heteroaryl-X-heteroaryl, and heteroaryl-X-aryl wherein X is [C(R5)2]P, O, S, S(=0), S02, NR5, C=0, CF2, C(=0)NR5 or NR5C(=0) wherein p is 1 , 2 or 3 and wherein aryl and heteroaryl in each occurrence may be optionally substituted and further wherein aryl is preferably phenyl and heteroaryl is preferably 5-6-membered heteroaryl;R is H, d^alkyl, C2.4alkenyl, C2. alkynyl, or C3.7cycloalkyl preferably C^alkyl;R5 in each occurrence is independently H or optionally substituted C^alkyl;R6 is selected from H, C^alkyl, C2.6alkenyl, C2.6alkynyl, d ealkoxy, d ealkylhalo, d- 6alkoxyhalo, R8, Ci-6alkyl-R8, d-6alkyl-OR8, Ci_6alkyl-SR8, .6alkyl-S02R8, d-6alkyl-N(R8 1.6alkyl-0(C=0)-R8, d-ealkyl- C(=0)N(R8)2, Ci.6alkyl-NR5S02-R8, Ci_6alkyl-S02NR5-R8 and d- 6alkyl-C(=0)NR5S02R8 and wherein alkyl, alkenyl, alkynyl, alkoxy, aryl, cycloalkyi, heterocyclyl and heteroaryl in each occurrence of R6 may be optionally substituted;R8 in each occurrence is independently H, an optionally an optionally substituted d ealkyl, an optionally substituted C2.6alkenyl, an optionally substituted (d-6alkyl)q-aryl, an optionally substituted (d-6alkyl)q-d-7cycloalkyl, an optionally substituted (d-6alkyl)q-5-6-membered heterocyclyl or an optionally substituted (d-6alkyl)q-5-6-membered heteroaryl, preferably each R8 is independently H or an optionally substituted Ci_6alkyl;q is 0 or 1 ; andR7 is selected from optionally substituted (d-6alkyl)q-N(R5)2, optionally substituted (d- 6alkyl)q-aryl, optionally substituted (d-6alkyl)q-5-6-membered heteroaryl, optionally substituted (C1.6alkyl)q-NR5C(=0)-(C1.6alkyl)q-aryl, optionally substituted (Ci_6alkyl)q- optionally substituted (d-6alkyl)q-C(=0)NR5-(d-6alkyl)q-5-6- membered heteroaryl and optionally substituted (d-6alkyl)q-NR5C(=0)-(d-6alkyl)q-5-6- membered heteroaryl.
바이러스 폴라머라아제 저해제본 발명은 화학식 (I)의 바이러스 폴리머라아제 저해제들, 이의 염들, N-옥사이드들, 용매화물들, 수화물들, 라세미체들, 거울상 이성질체들 또는 이성질체들, 이들의 제조 방법 및 C형 간염 바이러스(Hepatitis C virus, HCV) 감염들과 같은 플라비비리대 바이러스 감염들의 치료에서의 이들의 용도에 대한 것이다:화학식 (I)의 화합물, 이의 염들, N-옥사이드들, 용매화물들, 수화물들, 라세미체들(racemates), 거울상 이성질체들 또는 이성질체들:Z1 및 Z2는 각각 독립적으로 C-H, C-할로, C-C1-4알킬, C-C1-4알킬할로, C-C1-4알콕시, C-C1-4알콕시할로 및 N으로부터 선택된 것이고; R1은 H, C1-6알킬, C2-6알케닐, C2-6알키닐, C1-6알콕시, 할로, C1-4알킬할로, C1-4알콕시할로, C3-7사이클로알킬, C3-7사이클로알케닐,5-6-원 헤테로사이클릴 및 5-6 원 헤테로아릴로부터 선택된 것이고, 여기에서 각 존재에서의 알킬, 알케닐, 알키닐, 알콕시, 사이클로알킬, 헤테로사이클릴 및 헤테로아릴은 임의로 치환될 수 있으며;R2는 할로, C1-6알킬, C2-6알케닐, NO2, N(R5)2,NR5R6, NR6(SO2R5), SO2N(R8)2, SR8, C(R5)2SO2R8, NR5C(=O)R8, 임의로 치환된 아릴, 임의로 치환된 아릴-R7, 임의로 치환된 헤테로사이클릴, 임의로 치환된 헤테로사이클릴-R7, 임의로 치환된 헤테로아릴 및 임의로 치환된 헤테로아릴-R7로부터 선택된 것이고;R3은 아릴, 아릴-X-아릴, 아릴-X-헤테로아릴, 헤테로아릴, 헤테로아릴-X-헤테로아릴, 및 헤테로아릴-X-아릴로부터 선택된 것이고, 여기에서 X는 [C(R5)2]p, O, S, S(=O), SO2, NR5, C=O, CF2, C(=O)NR5 또는 NR5C(=O)이고, p는 1, 2 또는 3이며, 각 존재에서 아릴 및 헤테로아릴은 임의로 치환될 수 있으며, 추가로 아릴은 바람직하게는 페닐이고 헤테로아릴은 바람직하게는 5-6-원 헤테로아릴이며;R4는 H, C1-4알킬, C2-4알케닐, C2-4알키닐, 또는 C3-7사이클로알킬, 바람직하게는 C1-4알킬이고;각 존재에서의 R5는 독립적으로 H 또는 임의로 치환된 C1-6알킬이고;R6은 H, C1-6알킬, C2-6알케닐, C2-6알키닐, C1-6알콕시, C1-6알킬할로, C1-6알콕시할로, R8, C1-6알킬-R8, C1-6알킬-OR8, C1-6알킬-SR8, C1-6알킬-S(=O)R8, C1-6알킬-SO2R8, C1-6알킬-N(R8)2, C1-6알킬-C(=O)-R8, C1-6알킬-O(C=O)-R8, C1-6알킬-C(=O)O-R8, C1-6알킬-C(=O)N(R8)2, C1-6알킬-NR5C(=O)-R8, C1-6알킬-NR5SO2-R8, C1-6알킬-SO2NR5-R8 및 C1-6알킬-C(=O)NR5SO2R8로부터 선택된 것이고, 여기에서 R6의 각 존재에서 알킬, 알케닐, 알키닐, 알콕시, 아릴, 사이클로알킬, 헤테로사이클릴 및 헤테로아릴은 임의로 치환될 수 있으며;각 존재에서의 R8은 독립적으로 H, 임의로 치환된 C1-6알킬, 임의로 치환된 C2-6알케닐, 임의로 치환된 (C1-6알킬)q-아릴, 임의로 치환된 (C1-6알킬)q-C3-7사이클로알킬, 임의로 치환된 (C1-6알킬)q-5-6-원 헤테로사이클릴 또는 임의로 치환된 (C1-6알킬)q-5-6-원 헤테로아릴이고, 바람직하게는 각 R8은 독립적으로 H 또는 임의로 치환된 C1-6알킬이고; q는 0 또는 1이며; 및 R7은 임의로 치환된 (C1-6알킬)q-N(R5)2, 임의로 치환된 (C1-6알킬)q-아릴, 임의로 치환된 (C1-6알킬)q-5-6-원 헤테로아릴, 임의로 치환된 (C1-6알킬)q-NR5C(=O)-(C1-6알킬)q-아릴, 임의로 치환된 (C1-6알킬)q-C(=O)NR5-(C1-6알킬)q-아릴, 임의로 치환된 (C1-6알킬)q-C(=O)NR5-(C1-6알킬)q-5-6-원 헤테로아릴 및 임의로 치환된 (C1-6알킬)q-NR5C(=O)-(C1-6알킬)q-5-6-원 헤테로아릴로부터 선택된 것임.