Abstract Pyrimidine and pyridine heterocycles are extensively exploited in drug research and development because of their ability to coordinate and their role in various biological processes. The study offers an innovative one‐step synthetic method and insight into mechanistic pathways for the synthesis of heterocyclic rings from o ‐amino cyano derivatives. In order to generate a diversity of indole‐substituted dipyrimido1,2‐ a :4′,5′‐ d pyrimidine and pyrimido4,5‐ d thiazolo3,2‐ a pyrimidine derivatives. Carbonitrile underwent sustained cyclization with a selection of reagents, including phenyl isothiocyanate, thiourea, carbon disulfide, guanidine nitrate, benzoyl chloride, urea, acetic anhydride, and active methylene compounds such as malononitrile, ethyl cyanoacetate, and benzylidene malononitrile. Cyclization typically involves an understanding of specific steps and the generation of intermediates that lead to the production of the above‐mentioned compounds. All synthesized compounds (2(a,b)–11(a,b)) were produced in good‐to‐moderate yield (51%–83%) and evaluated for in vitro anticancer activity against the A549 cell line (lung carcinoma). Compounds 3a, 6a, 7a, 8a, 2b, 3b, 7b, 8b, and 10b exhibited potential efficacy. Among them, 3a was found to be the most cytotoxic (IC 50 = 5.988 ± 0.12 µM). The article outlined new tandem approaches based on intramolecular cyclization that open up the possibility for tricyclic derivatives with highly functionalized pyridine and pyrimidine fragments. FTIR, 1 H NMR, 13 C NMR, and HRMS techniques were employed to validate the structural integrity.
Anjirwala et al. (2025) studied this question.