Synthesis and Evaluation of Novel Pyrrolo[2,3-d] and Thieno[2,3-d]Pyridazinones as in Vitro Antiproliferative Agents

Vittorio Dal Piaz,* Claudia Vergelli, Maria Paola Giovannoni, Claudio Biancalani, Agostino Cilibrizzi, Alessia Graziano and Nicoletta Cesari

Corresponding author: Dipartimento di Scienze Farmaceutiche, Facoltà di Farmacia, Università di Firenze,
Via Ugo Schiff 6, Sesto Fiorentino 50019, Firenze, Italy.

* Corresponding author: E-mail:;
Tel.: +39-055-4573681, Fax: +39-055-4573780

Two different types of novel heterocyclic-fused pyridazinones like pyrrolo[2,3-d] and thieno[2,3-d] derivatives were synthesized starting from their isoxazolo[3,4-d] precursors by oxidative cleavage with CAN followed by cyclocondensation of the five-membered system using bi-functional nucleophiles. The final compounds were preliminarily screened in vitro as antiproliferative agents under the protocols of the NCI using three human cell lines of CNS, lung and breast cancers. None of the compounds was able to reduce the growth at value < 32% which was the cut-off for a more in depth in vitro screening.

Keywords: Thieno[2,3-d]pyridazinones, pyrrolo[2,3-d]pyridazinones, synthesis, in vitro antiproliferative agents.