Preparation of benzofuropyrimidinones as protein kinase inhibitors.

Abstract

Title compds. I [R1 = H or alkyl; R2 = aminocarbonylalkylaminoalkyl, aminoalkylaminoalkyl, dialkylaminoalkylaminoalkyl, carboxyalkylaminoalkyl, cycloakylaminoalkyl, etc.; or R1 and R2, together with the carbon atoms to which they are attached, join to form a 5-membered heterocycloalkyl ring; R3a = halo, No2, (un)substituted alkyl, alkoxy, alkynyl; R3b, R3c and R3 independently = H, OH, N+(O)OH, alkoxyl, or halo; or R3a = H and R3b, R3 and R3 independently = CF3, OH, alkoxy, or halo; or R3a and R3, together with the carbons to which they are attached, join to form a (un)substituted 5-membered heteroaryl or a 5- to 6-membered heterocycloalkyl], and their pharmaceutically acceptable salts, are prepd. and disclosed for inhibiting protein kinases such as PIM, CDC7 or CK2. Thus, e.g., II was prepd. by condensation reaction of 8-bromo-2-(chloromethyl)[1]benzofuran[3,2-d]pyrimidin-4(3H)-one with pyrrolidine. The invention compds. were evaluated against the CDC7 enzyme in a chemiluminescence assay, e.g., II exhibited IC50 value of < 10000 nM. [on SciFinder(R)]