Oxadiazole derivatives as S1P1 receptor agonists

摘要

New compounds having the chemical structure of formula (I) or pharmaceutically acceptable salts or N-oxides thereof wherein
A is selected from the group consisting of -N-, -O- and -S-;
B and C independently are selected from the group consisting of -N- and -O-, with the proviso that at least two of A, B and C are nitrogen atoms;
G 1 is selected from the group consisting of nitrogen atoms and -CR C - groups, wherein R C represents a hydrogen atom, a halogen atom, a C 1-4 alkyl group or a C 1-4 alkoxy group;
R 1 is selected from the group consisting of hydrogen atoms, C 1-4 alkyl groups, C 1-4 alkoxy groups, C 3-4 cycloalkyl groups, and -NR d R e groups wherein R d and R e are independently selected from hydrogen atoms and C 1-4 alkyl groups;
R 2 and R 3 are independently selected from the group consisting of hydrogen atoms and C 1-4 alkyl groups;
R 4 , R 5 and R 7 are independently selected from the group consisting of hydrogen atoms, halogen atoms, C 1-4 alkyl groups, C 1-4 alkoxy groups and C 1-4 haloalkyl groups;
R 6 represents a C 1-4 alkyl group or a C 1-4 hydroxyalkyl group; or R 6 is selected from the group consisting of -S(O) 2 -NR a R b groups, -(CR f R g ) n -(CR h R i ) x -(CR j R k ) y -NR a R b groups,
-(CH 2 ) n -NR a R b groups, -O-(CH 2 ) n -NR a R b groups, -(CH 2 ) n -COOH groups, -(CH 2 ) n -NR a -CO-R b' groups, -(CH 2 ) n -NR a -(CH 2 ) p -(NH) q -SO-CH 3 groups and -(CH 2 ) n -CO-NR a R b groups, wherein
n, p, x and y are each independently integers from 0 to 3,
q is 0 or 1,
R f , R g , R h , R i , R j and R k independently represent hydrogen atoms or halogen atoms,
R b' is selected from the group consisting of methylsulphonyl groups, C 1-4 alkyl groups, C 1-4 hydroxyalkyl groups, C 1-4 carboxyalkyl groups, and C 1-4 haloalkyl groups;
R a and R b are independently selected from the group consisting of hydrogen atoms, methylsulphonyl groups, C 1-4 alkyl groups, C 1-4 hydroxyalkyl groups, C 1-4 carboxyalkyl groups, and C 1-4 haloalkyl groups, or
R a and R b together with the nitrogen atom to which they are attached form a 4 to 6 membered, saturated heterocyclic group, which contains, as heteroatoms, one or two nitrogen atoms and which is substituted by a carboxyl group or a C 1-4 carboxyalkyl group; or
R c together with R 6 form a C 5-8 carbocyclic ring optionally substituted by - NHR' wherein R' represents a hydrogen atom or a 6 1-4 carboxyalkyl group.