Based on the prediction results (PASS program), a new series of α-aminophosphonate derivatives and azaphosphones was synthesized and evaluated as antitumor agents against breast-, cervical-, liver, and colon cancer diseases. The analgesic/antiinflammatory properties of the new phosphorylated pyrazoles were also investigated. The study demonstrated an efficient site selective method for making condensation products of phosphonate derivatives in high yields from carbodiimides and different types of HE reagents (74–78%) as well as dialkyl phosphites (54–65%) and hexaalkyltriamidophosphites (80–85%). Their antitumor properties against four carcinoma cell lines representing human-liver (HEPG2), -colon (HCT116), -breast (MCF7), and -cervix (HeLa) were investigated. The results showed that at least two out of the five tested phosphonates exhibited remarkable antitumor activity (IC₅₀: 4.15–6.95 μM mL⁻¹) when compared to the standard drugs (IC₅₀: 5.7–9.3 μM mL⁻¹). Nevertheless, four phosphonate products showed an analgesic capacity >80%, when compared to aspirin (73%) at the same dose of 100 mg kg⁻¹. Furthermore, QSAR results indicated that the fused azaphosphones, thiazolopyrimidine- and pyridine-α-aminophosphonate derivatives (6 of 11 tested compounds), possess inflammatory inhibitory potency (99–117%) when compared to the standard drug (100%) after 360 min.