Substituted (heterocycloalkyl)methyl azole derivatives as c5a receptor modulators

A compound of Formula IA:

• or a pharmaceutically acceptable salt thereof, wherein
• A is oxygen, sulfur or NR;
• R is C1-C7alkyl, C2-C7alkenyl, C2-C7alkynyl, C1-C6haloalkyl, (C3-C10carbocycle)C1-C4alkyl or (4- to 7-membered heterocycloalkyl)C1-C4alkyl, each of which is substituted with from 0 to 3 substituents independently chosen from hydroxy, halogen, amino, cyano, oxo, C1-C4alkyl, C1-C4alkoxy and C1-C2alkoxycarbonyl;
• x is 0, 1 or 2;
• J, K and each occurrence of L are chosen from oxygen, sulfur, NH and CH2;
• such that no more than one of J, K and L is chosen from oxygen, sulfur and NH;
• R1 is chosen from:
• i) hydrogen, hydroxy, halogen, amino, cyano, nitro, —CHO, —CONH2, C1-C6haloalkyl and C1-C6haloalkoxy;
• ii) C1-C6alkyl, C2-C7alkenyl, C2-C7alkynyl, C2-C6alkanoyl, C1-C6alkoxy, (C3-C7cycloalkyl)C0-C4alkyl, (4- to 10-membered heterocycloalkyl)C0-C4alkyl, mono- and di-(C1-C6alkyl)aminoC0-C6alkyl, mono- and di-(C1-C6alkyl)carboxamide, C1-C6alkoxycarbonyl, —SOn(C1-C6alkyl), —NHSOnC1-C6alkyl, —(C0-C6alkyl)SOn(C1-C6alkyl), —SOnN(C1-C6alkyl)(C1-C6alkyl), and —SOn-phenyl, wherein each n is independently 0, 1 or 2, and each of which is substituted with from 0 to 3 substituents independently chosen from hydroxy, halogen, amino, cyano, oxo, C1-C4alkyl, C1-C4alkoxy and C1-C2alkoxycarbonyl;
• and
• iii) naphthyl, phenyl and 5- to 10-membered heteroaryl, each of which is substituted with from 0 to 3 substituents independently chosen from R11;
• R2 and R3 are independently hydrogen or C1-C6alkyl;
• R4 represents 1 substituent chosen from:
• i) C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxycarbonyl, (C3-C7cycloalkyl)C0-C4alkyl and hexahydro-1,3-benzodioxolyl;
• ii) aryl having 1 ring or 2 fused or pendant rings;
• iii) (4- to 10-membered heterocycloalkyl)C0-C4alkyl;
• iv) phenyl fused to a 5- to 7-membered saturated or partially unsaturated ring that (a) has 0, 1 or 2 ring atoms independently chosen from N, O and S, with remaining ring atoms being carbon, and (b) is substituted with from 0 to 3 substituents independently chosen from halogen, C1-C8alkyl, C1-C8alkoxy, C1-C8haloalkyl, C1-C8haloalkoxy;
• v) (5- to 10-membered heteroaryl)C0-C4alkyl, having 1 ring or 2 fused or pendant rings, from 5 to 7 members in each ring, and in at least one ring from 1 to 3 heteroatoms independently selected from N, O, and S, wherein R4 is not pyrimidyl;
• and
• vi) groups that are taken together with an R5 moiety to form a fused phenyl or pyridyl ring;
• wherein each of i), ii), iii), iv), v) and vi) is substituted with from 0 to 3 substituents independently chosen from R11;
• R5 represents from 0 to 3 substituents independently chosen from hydroxy, halogen, amino, cyano, nitro, —CHO, —CONH2, C1-C2haloalkyl, C1-C2haloalkoxy, C1-C6alkyl, C1-C6alkoxy, C3-C7cycloalkylC0-C4alkyl, mono- and di-(C1-C6alkyl)aminoC0-C6alkyl, optionally substituted phenyl, and groups that are taken together with R4 to form a fused, optionally substituted phenyl or pyridyl ring;
• and
• Ar1 represents
• i) phenyl or naphthyl, each of which is substituted with from 0 to 3 substituents independently chosen from amino, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, C1-C2haloalkoxy, —COOH, —CONH2, mono- and di-(C1-C4alkyl)amino, C2-C4alkanoyl, C1-C4sulfonate, C1-C4alkylsulfonyl, C1-C4alkylsulfinyl, C1-C4alkylthio, C3-C6alkanone, C2-C4alkyl ether, C2-C4alkanoyloxy, C1-C4alkoxycarbonyl and C1-C6alkylcarboxamide;
• ii) phenyl fused to a 5- to 7-membered saturated or partially unsaturated ring that (a) has 0, 1 or 2 ring atoms independently chosen from N, O and S, with remaining ring atoms being carbon, and (b) is substituted with from 0 to 3 substituents independently chosen from halogen, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl and C1-C2haloalkoxy;
• or
• iii) heteroaryl, having 1 ring or 2 fused or pendant rings, from 5 to 7 members in each ring, and in at least one ring from 1 to 3 heteroatoms independently selected from N, O, and S;
• wherein each of ii) and iii) is substituted with from 0 to 3 substituents independently chosen from R11;
• and
• R11 is independently chosen at each occurrence from hydroxy, halogen, amino, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, —COOH, —CONH2, —SO2NH2, mono- and di-(C1-C6alkyl)amino, C2-C6alkanoyl, C1-C6sulfonate, C1-C6alkylsulfonyl, C1-C6alkylsulfinyl, C1-C6alkylthio, C3-C6alkanone, C2-C6alkyl ether, C2-C6alkanoyloxy, C1-C6alkoxycarbonyl and C1-C6alkylcarboxamide.