| abstract |
The compounds described herein are useful for modulating the activity of Btk and for treating associated diseases, with excessive activity of Btk. The compounds are also useful for treating inflammatory and autoimmune diseases associated with aberrant proliferation of B cells, for example rheumatoid arthritis. Compositions containing the compounds of the formula (1) and at least one carrier, diluent or excipient are also described. Claim 1: A compound of the formula (1), wherein - - - - - is a single bond or a double bond; X is CH, CH2 or N; R is H, -R1, -R1-R2-R3, -R1-R3 or -R2-R3; R1 is aryl, heteroaryl, bicyclic heteroaryl, cycloalkyl or heterocycloalkyl, each of which is optionally substituted by one or more lower alkyl, hydroxy, hydroxyalkyl lower, lower alkoxy, halogen, nitro, amino, amido, cyano, oxo or lower haloalkyl; R2 is -C (= O), -C (= O) O, -C (= O) NR2 ', -NHC (= O) O, -C (R2') 2, -O, -S, -C (= NH) NR2 'or -S (= O) 2; each R2 ’is independently H or lower alkyl; R3 is H or R4; R4 is lower alkyl, lower haloalkyl, lower alkoxy, amino, (lower alkyl) -amino, cycloalkylamino, di (lower alkyl) -amino, aryl, arylalkyl, alkylaryl, heteroaryl, alkyl-heteroaryl, heteroaryl-alkyl, cycloalkyl, alkyl- cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, alkyl-heterocycloalkyl, heterocycloalkyl-alkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, spirocycloalkyl, spiroheterocycloalkyl, or spiroheterocycloalkyl bicyclic, each of which is lower or lower, is optionally substituted by lower or lower alkyl -amino, di (lower alkyl) -amino, hydroxy, lower hydroxyalkyl, lower alkoxy, lower alkanoyl, halogen, nitro, amino, amido, acyl, cyano, oxo, sulfonyl, lower alkylsulfonyl, guanidino, hydroxylamino, carboxy, carbamoyl , carbamate, lower haloalkoxy, heterocycloalkyl or lower haloalkyl; two lower alkyl groups together can form a ring; Y4 is Y4a, Y4b, Y4c or Y4d; Y4a is H or halogen; Y4b is lower alkyl, optionally substituted by one or more substituents chosen from the group consisting of lower haloalkyl, halogen, hydroxy, amino, cyano and lower alkoxy; Y4c is lower cycloalkyl, optionally substituted by one or more substituents chosen from the group consisting of lower alkyl, lower haloalkyl, halogen, hydroxy, amino, cyano and lower alkoxy; and Y4d is amino, optionally substituted by one or more lower alkyl, lower alkoxy alkyl or lower hydroxyalkyl; or a pharmaceutically acceptable salt thereof. |