New triamino-pyrimidine derivatives are cell division cycle 25 phosphatase inhibitors useful for treating or preventing e.g. cancer, neurodegenerative diseases, parasitic diseases, graft rejection, inflammatory diseases or allergies

摘要

Triamino-pyrimidine derivatives (I) and their racemic forms and/or enantiomers are new. Triamino-pyrimidine derivatives of formula (I) and their racemic forms and/or enantiomers are new. R 1aryl, aralkyl, heteroaryl or heteroarylalkyl (all optionally substituted by one or more halo, alkyl, haloalkyl, alkoxy, haloalkoxy, OH, CN, -SO 2NHR 10or NR 10R 11), alkyl, cycloalkyl, cycloalkylalkyl, CN, group of formula (a), -(CH 2) p-(CO) m-NR 8R 9, or -(CH 2) p-(CO) m-OR 8; r : 1 or 2; X : O or S; R 2H or alkyl; either R 8, R 9aryl, aralkyl, heteroaryl or heteroarylalkyl (all optionally substituted by one or more halo, alkyl, haloalkyl, alkoxy, haloalkoxy, OH, CN, -SO 2NHR 10or NR 10R 11), H, alkyl, haloalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl or group (a); or NR 8R 9heterocycloalkyl, 1,2,3,4-tetrahydro-isoquinoline or 1,2,3,4-tetrahydro-quinoline; m, p : 0 or 1, provided that m and n are not simultaneously zero; either R 10, R 11H or alkyl; or NR 10R 11heterocycloalkyl; R 3H or alkyl; either R4a, R4b, R5a, R5b : H, alkyl, aminoalkyl, or dialkylaminoalkyl; or NR4aR4b, NR5aR5b : heterocycloalkyl; and L : hydrocarbon linker optionally comprising one or more heteroatoms. An independent claim is included for the preparation of (I). [Image] [Image] ACTIVITY : Cytostatic; Neuroprotective; Antiparasitic; Virucide; Endocrine-Gen.; Immunosuppressive; Antiinflammatory; Antiallergic. MECHANISM OF ACTION : Cell division cycle 25 (CDC25) phosphatase inhibitor. The ability of (I) to inhibit CDC25 phosphatase was tested in vitro. The result showed that 5-({2-[{2-[(2,6-dipyrrolidin-1-ylpyrimidin-4-yl)amino]ethyl}(methyl)amino]ethyl}amino)-2-methyl-2,3-dihydro-1,3-benzothiazole-4,7-dione exhibited an IC 50value of = 20 nM.