TY - JOUR
T1 - Optimization of 4-amino-pyridazin-3(2H)-one as a valid core scaffold for FABP4 inhibitors
AU - Floresta, Giuseppe
AU - Crocetti, Letizia
AU - Silva, Renan Rodrigues de Oliveira
AU - Patamia, Vincenzo
AU - Mazzacuva, Francesca
AU - Chen, Yu Chee Sonia
AU - Vergelli, Claudia
AU - Cilibrizzi, Agostino
N1 - Funding Information:
This research has received funding for a scholarship to R.R.d.O.S from the Coordination for the Improvement of Higher Education Personnel—Brazil (CAPES‐PRINT, funding number 88887.570120/2020‐00).
Publisher Copyright:
© 2023 The Authors. Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
KW - computing assisted molecular design
KW - FABP4
KW - FABP4 inhibitors
KW - fatty acid binding protein
KW - pyridazinone
UR - http://www.scopus.com/inward/record.url?scp=85166415318&partnerID=8YFLogxK
U2 - 10.1002/ardp.202300314
DO - 10.1002/ardp.202300314
M3 - Article
C2 - 37518500
AN - SCOPUS:85166415318
SN - 0365-6233
VL - 356
JO - Archiv Der Pharmazie
JF - Archiv Der Pharmazie
IS - 10
M1 - 2300314
ER -