WO2010063352 2,5-diamino-substituted pyrido [4,3,D]pyrimidines as autotaxin inhibitors against cancer

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Scaffold: Pyridopyrimidine

Biological target:

Autotaxin or ectonucleotide pyrophosphatase/phosphodiesterase 2 (NPP2 or ENPP2)

Activity:

Inhibitor

Steps Conditions Reactions
a
Et3N, EtOH reflux, 48h Cyclization (Pyrimidine formation)
b DMF reflux 3h
c
NH4OAc, DMF reflux 4days Cyclization
d
150oC, 2days SNAr
e
POCl3, 90oC, 15h Chlorination
f
NH3 (25% in water), scelled tube, THF, 100oC, 15h SNAr
Steps Conditions Reactions
a
NH3 (25% in water), scelled tube, THF, 100oC, 15h SNAr
b 2N NaOH, THF, 50oC, 3h Saponification
c
EDCI.HCl, HOBt, 4-methylmorpholine, DMF, 48h Amide formation

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