4H-Chromenes (or 4H-benzopyranes) and their derivatives are components of many naturally occurring products, which have also been submitted to structural modifications to increase molecular diversity for potential medicinal properties. In this context and starting from the 2-amino-2H-benzopyran-3-carbonitrile platform, it was possible to built easily (20 min.) a new class of 4-imino-3-phenyl-3,4-dihydro-1H-chromeno[2,3-d]pyrimidine-2(5H)-thiones (55-70%) under microwave irradiation at 120°C in pyridine medium. Treatment of the amino-4H-chromene platform with orthoester gave the corresponding methanimidate intermediate, which is converted into formamidine derivatives (63-85%) from various cyclic secondary amines or into N-3 substituted 4H-benzopyrano[2,3-d]pyrimidine-4(5H)-imines (49-94%) under microwave irradiation (50-120 °C, 30 min.). The biological properties of all products were explored by in vitro cancer assays against a panel of seven tumor cell lines (Huh 7D12, Caco2, MDA-MB231, HCT116, PC3, NCI-H727, HaCat, fibroblasts which are representative of different cancers: leukemia, melanona, and cancers of liver, colon, breast, prostate, lung, and kidney) and also by in vitro Serine/Threonine protein kinase inhibition assays (HsCDK5-p25, GSK3a/b, CLK1, HsHaspin, HsPIM1, HsAurora B). Some of these 2-imino- or 2-amino-2H-benzopyran-3-carbonitriles are active against tumor cell lines (Huh7, Caco 2, HCT 116) or protein kinases (CLK1).