: Current clinical research suggests that fatty acid-binding protein 4 inhibitors (FABP4is), which are of biological and therapeutic interest, may show potential in treating cancer and other illnesses. We sought to uncover new structures through the optimization of the previously reported 4-amino and 4-ureido pyridazinone-based series of FABP4is as part of a larger research effort to create more potent FABP4 inhibitors. This led to the identification of 14e as the most potent analog with IC50  = 1.57 μM, which is lower than the IC50 of the positive control. Advanced modeling investigations and in silico absorption, distribution, metabolism, and excretion - toxicity calculations suggested that 14e represents a potential candidate for in vivo studies such as FABP4i.

Optimization of 4-amino-pyridazin-3(2H)-one as a valid core scaffold for FABP4 inhibitors / Floresta, Giuseppe; Crocetti, Letizia; Silva, Renan Rodrigues de Oliveira; Patamia, Vincenzo; Mazzacuva, Francesca; Chen, Yu Chee Sonia; Vergelli, Claudia; Cilibrizzi, Agostino. - In: ARCHIV DER PHARMAZIE. - ISSN 0365-6233. - ELETTRONICO. - (2023), pp. e2300314-e2300328. [10.1002/ardp.202300314]

Optimization of 4-amino-pyridazin-3(2H)-one as a valid core scaffold for FABP4 inhibitors

Crocetti, Letizia
;
Vergelli, Claudia;
2023

Abstract

: Current clinical research suggests that fatty acid-binding protein 4 inhibitors (FABP4is), which are of biological and therapeutic interest, may show potential in treating cancer and other illnesses. We sought to uncover new structures through the optimization of the previously reported 4-amino and 4-ureido pyridazinone-based series of FABP4is as part of a larger research effort to create more potent FABP4 inhibitors. This led to the identification of 14e as the most potent analog with IC50  = 1.57 μM, which is lower than the IC50 of the positive control. Advanced modeling investigations and in silico absorption, distribution, metabolism, and excretion - toxicity calculations suggested that 14e represents a potential candidate for in vivo studies such as FABP4i.
2023
e2300314
e2300328
Floresta, Giuseppe; Crocetti, Letizia; Silva, Renan Rodrigues de Oliveira; Patamia, Vincenzo; Mazzacuva, Francesca; Chen, Yu Chee Sonia; Vergelli, Claudia; Cilibrizzi, Agostino
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1322451
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