초록 ▼

The present invention is directed to compounds of the formula I: [EQU1](wherein R1, R2, R3, R4, R5, R7, R8, X, n, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or

The present invention is directed to compounds of the formula I: [EQU1](wherein R1, R2, R3, R4, R5, R7, R8, X, n, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.

대표청구항 ▼

1. A compound of the formula I: [EQU53]wherein:X is selected from: -(C0-6 alkyl)-Y-(C0-6 alkyl)-, -(C0-6 alkyl)-C3-8 cycloalkyl-(C0-6 alkyl)-, C2-10 alkenyl, and C2-10 alkynyl, where the alkyl is unsubstituted or substituted with 1-7 substituents where the substituents are independently selected fr

1. A compound of the formula I: [EQU53]wherein:X is selected from: -(C0-6 alkyl)-Y-(C0-6 alkyl)-, -(C0-6 alkyl)-C3-8 cycloalkyl-(C0-6 alkyl)-, C2-10 alkenyl, and C2-10 alkynyl, where the alkyl is unsubstituted or substituted with 1-7 substituents where the substituents are independently selected from: (a) halo, (b) hydroxy, (c) -O-C1-3 alkyl, and (d) trifluoromethyl, and where Y is selected from: a single bond, -O-, -SO2-, -NR10-, -NR10-SO2-, -SO2-NR10-, -S-, and -SO-, and where R10 is independently selected from: hydrogen, C1-6 alkyl, benzyl, phenyl, and C1-6 alkyl-C3-6 cycloalkyl, which is unsubstituted or substituted with 1-3 substituents where the substituents are independently selected from: halo, C1-3 alkyl, C1-3 alkoxy and trifluoromethyl; R1 is selected from: (1) -CO2H, (2) -NO2, (3) -tetrazolyl, (4) -hydroxyisoxazole, (5) -SO2NHCO-(C0-3 alkyl)-R9, and (6) -P(O)(OH)2; where R9 is independently selected from: hydrogen, C1-10 alkyl, C3-6 cycloalkyl, C1-6 alkyl-C3-6 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl, benzyl or phenyl, which is unsubstituted or substituted with 1-3 substituents where the substituents are independently selected from: halo, C13 alkyl, C13 alkoxy and trifluoromethyl, R2 is selected from: (1) hydrogen, and (2) hydroxy; R3 is selected from the group consisting of: phenyl and heterocycle, which is unsubstituted or substituted with 1-7 substituents where the substituents are independently selected from: (a) halo, (b) trifluoromethyl, (c) hydroxy, (d) C1-3 alkyl, (e) -O-C1-3 alkyl, (f) -CO2R9, (g) -NR9R10, and (h) -CONR9R10; R4 and R5 are independently selected from: hydrogen, hydroxy, fluoro, C1-10 alkyl, C3-8 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl, phenyl, -(C1-6 alkyl)-phenyl, -(C1-6 alkyl)-C3-8 cycloalkyl, naphthyl, biphenyl, and heterocycle, which is unsubstituted or substituted with 1-7 of R11 where R11 is independently selected from: (a) halo, (b) trifluoromethyl, (c) hydroxy, (d) C1-3 alkyl, (e) -O-C1-3 alkyl, (f) -CO2R9, and (g) -CONR9R10, or where R4 and R5 may be joined together to form a 3-8 membered saturated ring which may be unsubstituted or substituted with 1-7 of R11, or where, if n is 1, R2 and R4 may be joined together to form a double bond; R7 is selected from: (1) hydrogen, (2) C1-6 alkyl, which is unsubstituted or substituted with 1-4 substituents where the substituents are independently selected from: hydroxy, cyano, and halo, (3) hydroxy, and (4) halo; R8 is selected from: hydrogen, C3-8 cycloalkyl, phenyl, naphthyl, biphenyl, and heterocycle, which is unsubstituted or substituted with 1-7 of R12 where R12 is independently selected from: (a) halo, (b) cyano, (c) hydroxy, (d) C1-6 alkyl, which is unsubstituted or substituted with 1-5 of R13 where R13 is independently selected from: halo, cyano, hydroxy, C1-6 alkoxy, -CO2H, -CO2(C1-6 alkyl), trifluoromethyl, and -NR9R10, (e) -O-C1-6 alkyl, which is unsubstituted or substituted with 1-5 of R13, (f) -CF3, (g) -CBF2, (h) -CH2F, (i) -NO2, (j) C0-6 alkyl-phenyl or C0-6 alkyl-heterocycle, which is unsubstituted or substituted with 1-7 substituents where the substituents are independently selected from: (i) halo, (ii) hydroxy, (iii) C1-6 alkyl, (iv) -O-C-6 alkyl, (v) -CF3, (vi) -OCF3, (vii) -NO2, (viii) -CN, (ix) -SO2-C1-6 alkyl, (x) -CO2R9, (xi) -NR9R10, (xii) -CONR9R10, (xiii) -SO2-NR9R10, and (xiv) -NR9-SO2-R10; (k) -CO2R9, (l) tetrazolyl, (m) -NR9R10, (n) -NR9-COR10, (o) -NR9-CO2R10, (p) -CO-NR9R10, (q) -OCO-NR9R10, (r) -NR9CO..CM:sh;NR9R10, (s) -S(O)m-R9, wherein m is an integer selected from 0, 1 and 2, (t) -S(O)2-NR9R10, (u) -NR9S(O)2-R10, and (v) -NR9 S(O)2-NR9R10; n is an integer selected from 1, 2, 3 and 4; x is an integer selected from 0, 1 and 2, and y is an integer selected from 0, 1 and 2, with the proviso that the sum of x and y is 2; and pharmaceutically acceptable salts thereof and individual diastereomers thereof.