COMPETITIVE BINDING ASSAY FOR IDENTIFYING INHIBITORS OF HCV POLYMERASE

摘要

A method for identifying compounds binding to HCV polymerase comprising the steps of:contacting said HCV polymerase or an analog thereof with a probe formula I:wherein A is O, S, N, NR1, or CR1, wherein R1 is defined herein;----- represents either a single or a double bond;R2 is selected from: H, halogen, R21, OR21, SR21, COOR21, SO2N(R22)2, N(R22)2, CON(R22)2, NR22C(O)R22 or NR22C(O)NR22 wherein R21 and each R22 is defined herein;B is NR3 or CR3, wherein R3 is defined herein;with the proviso that, when A is not N, then one of A or B is either CR1 or CR3, K is N or CR4, wherein R4 is defined herein;L is N or CR5, wherein R5 has the same definition as R4 defined above;M is N or CR7, wherein R7 has the same definition as R4 defined above;R5 is C(Y1)Z wherein Y1 is O or S; and Z is N(R6a)R6 or OR6, wherein R6a is H or alkyl or NR61R62 wherein R61 and R62 are defined herein; and R6 is H, alkyl, cycloalkyl, alkenyl, Het, alkyl-aryl, alkyl-Het;or R6 is wherein R7 and R8 and Q are as defined herein; Y2 is O or S;R9 is H, (C1-6 alkyl), (C3-7)cycloalkyl or (C1-6)alkyl-(C3-7)cycloalkyl, aryl, Het, (C1-6)alkyl-aryl or (C1-6)alkyl-Het, all of which optionally substituted with R90; or R9 is covalently bonded to either of R7 or R8 to form a 5- or 6-membered heterocycle;or a salt thereof; where the probe comprises a detectable label attached to any suitable position, whereby said probe binds to an HCV polymerase or an analog thereof and is capable of being displaced by an inhibitor thereof.