Bipiperidinyl-derivatives and their use as chemokine receptors inhibitors

摘要

Described is a compound of formula (I), wherein X is a direct bond;-CH2-;-CH2-CH2-;-CHR9-;-C(O)-;-O-;-NH-or NR9; R1 is optionally R10 and/or R11-substituted phenyl; optionally R10 and/or R11 -substituted heteroaryl; optionally R10 and/or R11-substituted heteroaryl N-oxide; or optionally R10 and/or R11-substituted naphthyl; R2 has one of the significances given for R1; or is optionally R10 and/or R11-substituted fluorenyl; or optionally R10- substituted adamantyl; R3 has one of the significances given for R1; or is optionally R10 and/or R11-substituted fluorenyl; R10-substituted adamantyl; each of R4, independently, has one of the significances of R5; or is CN; OH; OR9; F; Cl; Br; or I; each of R5, independently, is H; C1-C6 alkyl; C1-C6 hydroxyalkyl; C2-C6 alkoxyalkyl; C1-C6 halogenoalkyl; phenyl; benzyl; or heteroaryl; each of R6, independently, has one of the significances given for R4; each of R7, independently, has one of the significances given for R5; R8 is H; C1-C6 alkyl; C2-C6 alkenyl; C2-C6 alkynyl; phenyl; benzyl; CN; CH2NH2; CH2NHR9; CH2NR9R9; CH2NHC(O)R9; CH2NR9C(O)R9; CH2NHC(O)NHR9; CH2NR9C(O)NHR9; CH2NR9C(O)NR9R9 ; CH2NHC(O)OR9; CH2NR9C(O)OR9; CH2NHSO2R9; CH2N(S02R9)2; or CH2NR9SO2R9; each R9, independently, is C1-C6 alkyl; C3-C6 cycloalkyl; C2-C6 alkenyl; C2-C6 alkynyl; phenyl; benzyl; heteroaryl; or CF3; R1O represents 1 to 4 substituents independently selected from C1-C6 alkyl ; C1-C6 hydroxyalkyl; C2-C6 alkoxyalkyl; C1- C6 halogenoalkyl; C1-C6 cycloalkyl; C2-C6 alkenyl; C3-C6 cycloalkenyl; C2-C6 alkynyl; phenyl; heteroaryl; heteroaryl N- oxide; F; Cl; Br; I; OH; OR9; CONH2; CONHR9; CONR9R9; OC(O)R9; OC(O)OR9; OC(O)NHR9; OC(O)NR9R9; OS02R9; COOH; COOR9; CF3; CHF2; CH2F; CN; NO2; NH2; NHR9; NR9R9; NHC(O)R9; NR9C(O)R9; NHC(O)NHR9; NHC(O)NH2; NR9C(O)NHR9; NR9C(O)NR9R9; NHC(O)OR9; NR9C(O)OR9; NHS02R9; N(S02R9)2; NR9SO2R9; SR9; S(O)R9; S02R9; Si(CH3)3 and B(OC(CH3)2)2; R11 represents two adjacent substituents which form an annulated 4-7 membered nonaromatic ring optionally containing up to two heteroatoms selected independently from N,O and S; and Y is a direct bond;-C(O)- ;-C (O) CH2- ;-S (O)- ;-S (02)- ;-C (S)-; -CH2- ;-C (-CH2-CH2-)- ;-CH (R5)- or-C (R4)2-, in free form or in salt form. The compound is described to be used as a chemokine inhibitor in the preparation of pharmaceutical compositions for preventing or treating acute or chronic rejection, autoimmune diseases, cancer or infectious diseases.