| abstract |
The present invention relates to compounds of the formula I, their pharmaceutically acceptable salts and solvates, wherein the substituents typically include: A is a monocyclic or bicyclic ring system containing at least two nitrogen atoms; X is CHR b, CH 2 CH R b or CH = C (R b); wherein R b is hydrogen, alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, alkylenaryl, or alkyleneheteroaryl; Y is absent or S, SO, SO 2, NH, O, C (= O), OC (= O), C (= O) O or NHC (= O) CH 2 S; R1 and R2 are independently hydrogen, alkyl, aryl, heteroaryl, halogen, or R1 and R2 together form an alkylene or alkenylene chain which is part of a ring; R3 is hydrogen; or optionally substituted alkyl, cycloalkyl, heterocycloalkyl, alkylene-cycloalkyl, alkenyl, alkylene-aryl, arylalkyl, aryl, heteroaryl. The compounds of the present invention selectively inhibit the activity of the PI3Kd isoenzyme in cells, especially leukocytes, osteoclasts and cancer cells. Thus, the present invention relates to in vitro and ex vivo methods of inhibiting PI3Kd activity and to the use of the compounds of formula I in the preparation of pharmaceutical compositions which selectively inhibit PI3Kd activity, such as for the treatment of diseases mediated by PI3Kd activity such as immune and inflammatory diseases. . SHE |