Roberta Mazzucato

A Journey through Scaffolds: Indolines, Pyrrolidines, and Azetidines in the Quest for Inhaled DDR Inhibitors for IPF

Laura Carzaniga, Fabio Rancati, A. Rizzi, Roberta Mazzucato et autres

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, with excessive Extracellular Matrix (ECM) deposition impairing gas exchange, leading to lung failure. Current treatments are limited, with lung transplantation as the only cure. Discoidin Domain Receptors (DDR1/2), collagen-activated receptor tyrosine kinases, orchestrate …

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Macrocyclization: Enhancing Drug-like Properties of Discoidin Domain Receptor Kinase Inhibitors

Laura Carzaniga, Roberta Mazzucato, Valentina Mileo, Andrea Rizzi et autres

High Resolution Image Download MS PowerPoint Slide Macrocyclization, a well-established strategy for developing ligands against challenging drug targets, was employed to design macrocyclic alternatives to a linear discoidin domain receptor (DDR) inhibitor ( 1 ) with potential applications in treating fibrotic diseases. …

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Discovery of CHF-6523, an Inhaled Selective PI3Kδ Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease

Paolo Bruno, Daniele Pala, Alessandra Micoli, Mauro Corsi et autres

The design of inhaled selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitors for the treatment of inflammatory lung diseases was pursued. Knowledge-based design of a novel isocoumarin scaffold that was able to adopt a propeller-shape topology ensured the desired PI3Kδ selectivity. Achievement of low …

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Discovery, Multiparametric Optimization, and Solid-State Driven Identification of CHF-6550, a Novel Soft Dual Pharmacology Muscarinic Antagonist and β2 Agonist (MABA) for the Inhaled Treatment of Respiratory Diseases

Laura Carzaniga, Ian D. Linney, A. Rizzi, Wolfgang Schmidt et autres

Clinical guidelines for COPD and asthma recommend inhaled β-adrenergic agonists, muscarinic antagonists, and, for frequent exacerbators, inhaled corticosteroids, with the challenge of combining them into a single device. The MABA (muscarinic antagonist and β 2 agonist) concept has the potential to simplify …

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Application of an “inhalation by design” approach to the identification and in-vitro evaluation of novel purine based PI3Kδ inhibitors

Roberta Mazzucato, Marinella Roberti, Anna Maria Capelli, Fabio Rancati et autres

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Preparation of Sterically Demanding 2,2-Disubstituted-2-Hydroxy Acids by Enzymatic Hydrolysis

Andrea Pinto, Immacolata Serra, Diego Romano, Martina Letizia Contente et autres

Preparation of optically-pure derivatives of 2-hydroxy-2-(3-hydroxyphenyl)-2-phenylacetic acid of general structure 2 was accomplished by enzymatic hydrolysis of the correspondent esters. A screening with commercial hydrolases using the methyl ester of 2-hydroxy-2-(3-hydroxyphenyl)-2-phenylacetic acid (1a) showed that crude pig liver esterase (PLE) was the …

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Direct Evidence of the Presence of Cross-Linked Aβ Dimers in the Brains of Alzheimer’s Disease Patients

Aurelio Vázquez de la Torre, Marina Gay, Sílvia Vilaprinyó-Pascual, Roberta Mazzucato et autres

Brain-derived amyloid-β (Aβ) dimers are associated with Alzheimer’s disease (AD). However, their covalent nature remains controversial. This feature is relevant, as a covalent cross-link has been proposed to make brain-derived dimers (brain dimers) more synaptotoxic than Aβ monomers and would also make …

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SDS-PAGE analysis of Aβ oligomers is disserving research into Alzheimer´s disease: appealing for ESI-IM-MS

Rosa Pujol‐Pina, Sílvia Vilaprinyó-Pascual, Roberta Mazzucato, Annalisa Arcella et autres

The characterization of amyloid-beta peptide (Aβ) oligomer forms and structures is crucial to the advancement in the field of Alzheimer´s disease (AD). Here we report a critical evaluation of two methods used for this purpose, namely sodium dodecyl sulfate polyacrylamide gel electrophoresis …

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