Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as c5a receptor modulators

A compound of formula (I) or a salt thereof:

• wherein
• X is N or CH;
• Z1 is N or CR1c;
• Z2 is N or CR1d, wherein at least one of Z1 and Z2 is not N;
• R1a is selected from the group consisting of hydrogen, C1-C6alkyl, C1-C6alkoxy, haloC1-C6alkyl, haloC1-C6alkoxy, cyano or halogen;
• R1b is selected from the group consisting of hydrogen, amino, hydroxy, C1-C6alkyl, C1-C6alkoxy, and mono- and di-C1-C4alkylamino;
• R1c is hydrogen, halogen or C1-C6alkyl;
• R1d is selected from the group consisting of hydrogen, halogen, C1-C6alkyl, and C1-C6alkoxy;
• R1e is selected from hydrogen, halogen, cyano, C1-C6alkyl, haloC1-C6alkyl, C1-C6alkoxy and haloC1-C6alkoxy, sulfone, C3-C7cycloalkyl;
• or
• R1a and R1b taken in combination form a 5 member saturated or unsaturated heterocyclic ring having one or two ring heteroatoms selected from N, O or S, which heterocyclic ring is substituted with 0, 1, or 2 independently selected C1-C6alkyl or halogen substituents;
• wherein at least one of R1a and R1e is not hydrogen;
• R2 is selected from the group consisting of hydrogen, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C3-C7cycloalkyl, C3-C7cycloalkylC1-C4alkyl and (CH2)pNR2aR2b, wherein each alkyl and alkoxy group is substituted with 0 or 2 substituents selected from the group consisting of hydroxy, halogen, and C1-C4alkoxy, amino, mono- and di-C1-C4 alkylamino;
• p is 0 or 1;
• R2a is hydrogen, C1-C6alkyl or hydroxyC1-C6alkyl;
• R2b is hydrogen, C1-C6alkyl, C3-C7cycloalkyl or C3-C7cycloalkylC1-C4alkyl, wherein each alkyl is unsubstituted or substituted with hydroxy, C1-C4alkoxy, C1-C4alkoxycarbonyl, or heterocycle wherein the heterocycle is a saturated, unsaturated or aromatic five or six member ring having 1 or 2 ring heteroatoms selected from N, O or S and is unsubstituted or substituted with 1 or 2 independently selected C1-C4alkyl substituents;
• or
• NR2aR2b taken in combination form a 4 to 8 member saturated heterocyclic ring system having 1 or 2 rings and 0 or 1 additional ring heteroatoms selected from N, O or S, the saturated heterocyclic ring system is unsubstituted or substituted with 1-4 substituents independently selected from the group consisting of C1-C4alkyl, hydroxy, C1-C4alkoxy, C1-C4alkoxyC1-C4alkyl, hydroxyC1-C4alkyl, halogen, amino, mono- and di-C1-C4alkylamino, C1-C4alkoxycarbonyl, C1-C4alkanoyl, S(O)2C1-C4alkyl, CH2C(O)(C1-C4alkoxy) and CH2C(O)NH2;
• R3 is selected from the group consisting of substituted phenyl, substituted heteroaryl, and phenylC1-C3alkyl, wherein the heteroaryl is selected from pyridyl, pyrazolyl, imidazolyl, tetrazolyl, oxazolyl, and isoxazolyl, and wherein each phenyl or heteroaryl group is substituted with 1, 2 or 3 substituents which are independently selected from the group consisting of C1-C4alkyl, C1-C4alkoxy, halogen, cyano, haloC1-C4alkyl, haloC1-C4alkoxy, hydroxyC1-C4alkyl, C1-C4alkoxyC1-C4alkyl, C3-C6cycloalkyl, and saturated oxacycle having 4, 5, or 6 ring atoms and one ring oxygen, which oxacycle is unsubstituted or substituted with 1 or 2 independently selected C1-C4alkyl substituents, and wherein each phenyl or heteroaryl comprises at least one non-hydrogen substituent ortho to the point of attachment to the remainder of the compound of formula (I);
• R4 is hydrogen or C1-C4alkyl;
• R5 is hydrogen;
• or
• R4 and R5 taken in combination are oxo;
• and
• R6 is hydrogen at each occurrence or CR62, taken in combination, form a divalent carbonyl.