Tropane derivatives useful in therapy
View Patent ↗The present invention provides compounds of formula (I) wherein X, Y, R 1 , R 2 and R 3 are as defined hereinabove. The compounds of the present invention are modulators, especially antagonists, of the activity of chemokine CCR5 receptors. Modulators of the CCR5 receptor may be useful in the treatment of various inflammatory diseases and conditions, and in the treatment of infection by HIV and genetically related retroviruses.
1. A compound of formula (VII), (IX), (XI) or (XIX):
wherein X and Y are selected from CH 2 and NR 4 such that one of X and Y is CH 2 and the other is NR 4 ;
R 3 C 1-4 alkyl substituted by 0 to 3 fluorine atoms;
R 4 is independently R 5 ; COR 5 ; CO 2 R 5 ; CONR 6 R 7 ; SO 2 R 5 ; or (C 1-6 alkylene)phenyl, wherein phenyl is substituted by 0 to 3 atoms or groups selected from C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, halogen, CF 3 , OH, CN, NR 6 R 7 , COR 7 , CO 2 R 7 or CONR 6 R 7
R 5 is C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl; C 3-7 cycloalkyl; a 5 or 6-membered aromatic heterocycle; or a 4 to 7-membered saturated heterocycle; wherein said alkyl, alkenyl, alkynyl and cycloalkyl are substituted by 0 to 3 atoms or groups selected from oxo, halogen, CF 3 , OR 7 , CN, NR 6 R 7 , COR 7 , CO 2 R 7 or CONR 6 R 7 ; wherein said heterocycles contain one to three heteroatoms selected from N, O or S; and wherein said heterocycles are substituted by 0 to 3 atoms or groups selected from C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, halogen, CF 3 , OH, CN, NR 6 R 7 , COR 7 , CO 2 R 7 or CONR 6 R 7 ;
R 6 is H; C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl; C 3-7 cycloalkyl; a 5 or 6-membered aromatic heterocycle; or a 4 to 7-membered saturated heterocycle; wherein said alkyl alkenyl, alkynyl and cycloalkyl are substituted by 0 to 3 atoms or groups selected from oxo, halogen, CF 3 , OR 7 , CN, COR 7 or CO 2 R 7 ; wherein said heterocycles contain one to three heteroatoms selected from N, O or S; and wherein said heterocycles are substituted by 0 to 3 atoms or groups selected from C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, halogen, CF 3 , OH, CN, COR 7 or CO 2 R 7 ;
R 7 is H or C 1-6 alkyl;
or when R 6 and R 7 are both attached to the same N atom, NR 6 R 7 may also represent a 5 to 7 membered, saturated, partially unsaturated or aromatic, heterocyde containing from 0 to 2 additional heteroatoms selected from O, N or S;
and Pg is an amino protecting group.
2. A compound of formula (II), (IV), (V), (VI), (XVII), (XXII), (XXIV), (XXV) or (XXVI):
wherein
X and Y are selected from CH 2 and NR 4 such that one of X and Y is CH 2 and the other is NR 4 ;
R 1 and R 4 are independently R 5 ; COR 5 ; CO 2 R 5 ; CONR 6 R 7; SO 2 R 5 ; or (C 1-6 alkylene)phenyl, wherein phenyl is substituted by 0 to 3 atoms or groups selected from C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, halogen, CF 3 , OH, CN, NR 6 R 7 , COR 7 , CO 2 R 7 or CONR 6 R 7 ;
R 2 is phenyl substituted by 0 to 3 atoms or groups selected from C 1-6 alkylcarbonyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, halogen, CF 3 , OH, CN, NR 5 R 7 , CO 2 R 7 or CONR 6 R 7 ;
R 3 is C 1-4 alkyl substituted by 0 to 3 fluorine atoms,
R 3 is C 1-4 alkyl substituted by 0 to 3 fluorine atoms;
R 5 is C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl; C 3-7 cycloalkyl; a 5 or 6-membered aromatic heterocycie; or a 4 to 7-membered saturated heterocycle; wherein said alkyl, alkenyl, alkynyl and cycloalkyl are substituted by 0 to 3 atoms or groups selected from oxo, halogen, CF 3 , OR 7 , CN, NR 6 R 7 , COR 7 , CO 2 R 7 or CONR 6 R 7 ; wherein said heterocycles contain one to three heteroatoms selected from N, O or S; and wherein said heterocycles are substituted by 0 to 3 atoms or groups selected from C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, halogen, CF 3 , OH, CN, NR 6 R 7 , COR 7 , CO 2 R 7 or CONR 6 R 7 ;
R 6 is H; C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl; C 3-7 cycloalkyl; a 5 or 6-membered aromatic heterocycle; or a 4 to 7-membered saturated heterocycle; Therein said alkyl, alkenyl, alkynyl and cycloalkyl are substituted by 0 to 3 atoms or groups selected from oxo, halogen, CF 3 , OR 7 , CN, COR 7 or CO 2 R 7 ; wherein said heterocycles contain one to three heteroatoms selected from N, O or S; and wherein said heterocycles are substituted by 0 to 3 atoms or groups selected from C 1-6 alkyl C 1-6 alkylcarbonyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, halogen, CF 3 , OH, CN, COR 7 or CO 2 R 7 ;
R 7 is H or C 1-6 alkyl
or, when R 6 and R 7 are both attached to the same N atom, NR 6 R 7 may also represent a 5 to 7 membered, saturated, partially unsaturated or aromatic, heterocycle containing from 0 to 2 additional heteroatoms selected from O, N or S,
and Pg is an amino protecting group.