Design, Synthesis, Anticancer Screening, and Virtual Analysis of New 7-Sulfonyldiazepane- and 7-Sulfonylpiperazine-Substituted Oxazolo[4,5-d]pyrimidines

Abstract

The design of novel anticancer agents has been advanced by applying machine learning techniques, leading to several classification and regression structure-activity relationship models specifically tailored for the human glioblastoma SNB-75. Using these models, a virtual library was screened to identify compounds with potential activity against the SNB-75 cell line. A series of new 7-sulfonyldiazepane- and 7-sulfonylpiperazine-substituted oxazolo[4,5-d]pyrimidines were synthesized and evaluated for their antitumor activity against the NCI-60 cell lines. 2-(4-Methylphenyl)-5-phenyl-7-[4-(phenylsulfonyl)piperazin-1-yl][1,3]oxazolo[4,5-d]pyrimidine demonstrated cytotoxic activity and a high level of selectivity to CNS SNB-75, while 2-(4-methylphenyl)-7-[4-(methylsulfonyl)-1,4-diazepan-1-yl]-5-phenyl[1,3]oxazolo[4,5-d]pyrimidine showed very high activity against the non-small lung cancer NCI-H460 cell line. The compounds met druglike criteria according to ADMET analysis. Molecular docking investigations of synthesized compounds demonstrated complex formation with carbonic anhydrase XII as a potential mechanism. This makes these compounds attractive for further study as agents against non-small cell lung cancer and CNS cancer.

Key words

oxazolo[4,5-d]pyrimidines - QSAR - anticancer screening - COMPARE correlation - docking

Publication History

Received: 07 July 2025

Accepted after revision: 19 August 2025

Accepted Manuscript online:
21 August 2025

Article published online:
13 October 2025

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