Climate-induced conservation risks of historic reinforced concrete buildings: Preliminary results from literature review

Environmental conditions can favour different kinds of deterioration in historic reinforced concrete structures. This preliminary results from literature review are focused on the climate-induced risks affecting reinforced concrete buildings with respect to mechanical, chemical, and biological deterioration. To this purpose, a three-step process defined by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram, was used leading to the inclusion of 45 documents identified via the search engines Scopus and Web of Science. The outcomes highlight that chemical and mechanical decays are the most investigated ones, being mainly triggered by salt weathering and freezing-thawing cycles. It was found that experimental and theoretical approaches are often coupled to estimate climate-induced deterioration mechanisms, also considering environmental parameters. Finally, the literature search provides some milestones which can be used to evaluate gaps and research needs in the field of climate-induced conservative risks affecting reinforced concrete structures

Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition

Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series

Synthesis, HPLC enantioresolution and X-ray analysis of a new series of C5-methyl pyridazines as N-formyl peptide receptor (FPR) agonists

The synthesis of three racemates and the corresponding non chiral analogues of a C5-methyl pyridazine series is described here, as well as the isolation of pure enantiomers and their absolute configuration assignment. In order to obtain optically active compounds, direct chromatographic methods of separation by HPLC-UV were investigated using four chiral stationary phases (CSPs: Lux Amylose-2(®), Lux Cellulose-1(®), Lux Cellulose-2(®) and Lux Cellulose-3(®)). The best resolution was achieved using amylose tris(5-chloro-2-methylphenylcarbamate) (Lux Amylose-2(®)), and single enantiomers were isolated on a semipreparative scale with high enantiomeric excess, suitable for biological assays. The absolute configuration of optically active compounds was unequivocally established by X-ray crystallographic analysis and comparative chiral HPLC-UV profile. All compounds of the series were tested for formyl peptide receptor (FPR) agonist activity, and four were found to be active, with EC(50) values in the micromolar range

Synthesis, enantioresolution and activity profile of chiral 6-methyl-2,4-disubstituted pyridazin-3(2H)-ones as potent N-formyl peptide receptor agonists.

A series of chiral pyridazin-3(2H)-ones was synthesized, separated as pure enantiomers, and evaluated for N-formyl peptide receptor (FPR) agonist activity. Characterization of the purified enantiomers using combined chiral HPLC and chiroptical studies (circular dichroism, allowed unambiguous assignment of the absolute configuration for each pair of enantiomers). Evaluation of the ability of racemic mixtures and purified enantiomers to stimulate intracellular Ca(2+) flux in FPR-transfected HL-60 cells and human neutrophils and to induce β-arrestin recruitment in FPR-transfected CHO-K1 cells showed that many enantiomers were potent agonists, inducing responses in the sub-micromolar to nanomolar range. Furthermore, FPRs exhibited enantiomer selectivity, generally preferring the R-(−)-forms over the S-(+)-enantiomers. Finally, we found that elongation of the carbon chain in the chiral center of the active compounds generally increased biological activity. Thus, these studies provide important new information regarding molecular features involved in FPR ligand preference and report the identification of a novel series of FPR agonists