A novel series of annulated diphenylpyrazoles were designed and synthesized through various strategies. The
bifunctional enaminonitrile 1 used as the key intermediate to prepare the pyrrolopyrazole 2, pyrazolopyridine 3,
pyrazolothiazine 8, and pyrazolopyrimidine 9 derivatives through its cyclocondensation with ethyl chloroacetate, diethyl
malonate, and carbon disulfide under different conditions. The novel valuable derivatives 2 and 5 are subjected to
amylolysis, while compound 9 is used to synthesize tricyclic compounds. The reaction of 1 with sodium azide afforded the
tetrazole derivative 13. The behavior of 13 was studied with carbon disulfide, benzaldehyde and phenacyl bromide. The
condensation behavior of compound 1 with furfural, cyclohexanone, chloroacetyl chloride, benzyl chloride, benzoyl
chloride, ammonium hydroxide/H2O2, sulfuric acid (50%), sodium hydroxide (50%), triethyl orthoformate, and ammonium
thiocyanate have also been taken into consideration. These entire novel scaffolds have been proofed using Elemental
analysis, spectral data including IR, 1H-NMR in addition to 13C-NMR, and mass spectra. These new scaffolds were
screened for in vitro antimicrobial and cytotoxic activities. Most analogs revealed excellent to good results. Finally, TEM
investigations were screened and revealed that pyrazolopyrimidinethione derivative 9 showed completely lysed.