NZ505960A - Heterocyclyl substituted piperazin-2-one derivatives useful as factor Xa inhibitors - Google Patents

Abstract

A heterocyclyl substituted piperazin-2-one derivative or a pharmaceutically acceptable salt thereof, pharmaceutically acceptable prodrug thereof, an N-oxide thereof, a hydrate thereof or a solvate thereof has the formula (I) wherein: G1 and G2 are L1-Cy1 or L2-Cy2 provided that when R1 and R1a or R4 and R4a taken together form O or S, then G1 is L2-Cy2 and G2 is L1-Cy1 or when R2 and R2a or R3 and R3a taken together form O or S, then G1 is L1-Cy1 and G2 is or L2-Cy2; Cy1 and Cy2 are independently optionally substituted aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, fused arylcycloalkyl, fused arylcycloalkenyl, fused arylheterocyclyl, fused arylheterocyclenyl, fused heteroarylcycloalkyl, fused heteroarylcycloalkenyl, fused heteroarylheterocyclyl or fused heteroarylheterocyclenyl; L1 is O, NR5, -S(O)p, -S(O)pNR5-, -C(X)Y- or - L3-Q-L4-Q1-L5-, L3 and L5 are independently absent, optionally substituted alkylene, alkenylene or alkynylene; L4 is optionally substituted alkylene, alkenylene, or alkynylene; Q and Q1 are independently absent, NR5, -S(O)p, -S(O)pNR5- or -C(X)Y- A is CH or N; R1, R1a, R2, R2a, R3, R3a, R4 and R4a are independently hydrogen, carboxy, alkoxycarbonyl, Y1Y2NCO or optionally substituted alkyl, aryl, aralkyl, heteroaryl or heteroaralkyl or R1 and R1a, R2 and R2a, R3 and R3a or R4 and R4a taken together form O or S; m and n are independently 0 to 2, provided that m and n are not both 0 and further provided that when R1 and R1a taken together form O or S, n is 1 and when R4 and R4a taken together form O or S, m is 1; L2 is absent or -[C(R7)(R8)]q-Z-[C(R9)(R10)]q R5 to R10 are as defined in the specification, Y1 and Y2 are independently hydrogen, optionally substituted alkyl, aryl, aralkyl or heteroaralkyl, or Y1 and Y2 taken together with the N through which Y1 and Y2 are linked form a monocyclic heterocyclyl; X is O or S; Y is absent, O, S or NR5; Z is absent, alkenylene, optionally substituted alkynylene, O, S(O)p, NR5, -NR5C(O)- or-C(O)NR5-; x is 1 to 4; v is 2 to 4; p is 1 or 2 and q and r are independently 1 to 3, provided that q and r are not both 0. A pharmaceutical composition thereof is useful as a factor Xa inhibitors.