Factor IXa Inhibitors

A compound of the formula:

• wherein the dotted lines represent aromatic rings;
• X1 is N or C;
• X2 is N, NR11, or CR12;
• X3 is C or N;
• X4 is CR4aR4b, O or S;
• Y is heteroaryl or aryl, which is optionally substituted with one or two substituents independently selected from the group consisting of halo, R9, OR9, (C═O)NH2 and (C═O)OH;
• Z is heteroaryl, which is optionally substituted with one or two substituents independently selected from the group consisting of halo, oxo, R9, OR9, (C═O)NR9R10, (C═O)R9, (C═O)OR9, (C═O)heterocyclyl-OH and C3-6 cycloalkyl;
• or heterocyclyl, which is optionally substituted with one or two substituents independently selected from the halo, cyano, oxo or C1-6 alkyl;
• R1 is
• a) H,
• b) C1-6 alkyl, wherein said alkyl is optionally substituted with one to three substituents independently selected from the group consisting of halo and hydroxy,
• c) aryl, wherein said aryl is optionally substituted with one or two substituents independently selected from the group consisting of halo, R9, OR9 and (C═O)OR9, or
• d) heteroaryl, wherein said heteroaryl group is optionally substituted with one or two substituents independently selected from the group consisting of halo, R9, OR9, (C═O)NR9, (C═O)OR9 and C3-6 cycloalkyl (which is optionally substituted with R9);
• R2 is H, halo, hydroxy, cyano or C1-6 alkyl;
• R3 is H, halo, hydroxy, cyano or C1-6 alkyl;
• or R2 and R3 can be taken together with the carbon atoms to which they are attached to form a 5 or 6 membered cycloalkyl ring;
• R4a is H, halo, hydroxy, cyano or C1-6 alkyl;
• R4b is H, halo, hydroxy, cyano or C1-6 alkyl;
• R5 is H, halo, hydroxy, cyano or C1-6 alkyl;
• R6 is H, halo, hydroxy, cyano or C1-6 alkyl;
• R7 is H, halo, hydroxy, cyano or C1-6 alkyl;
• R8 is H, halo, hydroxy, cyano or C1-6 alkyl;
• R9 is H or C1-6 alkyl, which is optionally substituted with one to three substituents independently selected from the group consisting of halo and hydroxy;
• R10 is H or C1-6 alkyl, which is optionally substituted with one to three substituents independently selected from the group consisting of halo and hydroxy;
• R11 is hydrogen, C1-6 alkyl or C1-6 alkyl-(C═O)OR9;
• R12 is
• a) hydrogen,
• b) halo,
• c) cyano,
• d) (C═O)R9,
• c) (C═O)OR9,
• e) (C═O)NR9R10,
• f) SO2R9,
• g) C1-6 alkyl, which is optionally substituted with one to four substituents independently selected from the group consisting of halo, cyano, C3-6 cycloalkyl, OR9, NR9R10, (C═O)OR9, (C═O)NR9R10, CH═CH(C═O)OR9, CH═CH(C═O)NR9R10 and CF3,
• h) C2-6 alkenyl, which is optionally substituted with one to four substituents independently selected from the group consisting of halo, OR9, NR9R10, (C═O)OR9 and (C═O)NR9R10,
• i) heteroaryl, which is optionally substituted with one or two substitutents independently selected from the group consisting of halo, cyano, oxo, C3-6 cycloalkyl, R9, OR9, NR9R10, (C═O)R9 and (C═O)OR9,
• j) heterocyclyl, which is optionally substituted with one or two substituents independently selected from the halo, cyano, oxo or C1-6 alkyl,
• k) C3-6 cycloalkyl, or
• l) C(R9)═NOH;
• or a pharmaceutically acceptable salt thereof.