A Novel Prodrug of a nNOS Inhibitor with Improved Pharmacokinetic Potential
Abstract: Under different pathological conditions, aberrant induction of neuronal nitric oxide synthase (nNOS) generates overproduction of NO that can cause irreversible cell damage. The aim of this study was to develop an amidoxime prodrug of a potent nNOS inhibitor, the benzhydryl acetamidine. We synthesized the benzhydryl acetamidoxime, which was evaluated in vitro to ascertain the potential NOS inhibitory activity, as well as conducting bioconversion into the parent acetamidine. The prodrug was also profiled for in vitro physicochemical properties, by determining the lipophilicity, passive permeation through the human gastrointestinal tract and across the blood‐brain barrier by PAMPA, and chemical, enzymatic, and plasma stability. The obtained data demonstrate that the amidoxime prodrug shows an improved pharmacokinetic profile with respect to the acetamidine nNOS inhibitor, thus suggesting that it could be a promising lead compound to treat all those pathological conditions in which nNOS activity is dysregulated.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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A Novel Prodrug of a nNOS Inhibitor with Improved Pharmacokinetic Potential ; volume:15 ; number:22 ; year:2020 ; pages:2157-2163 ; extent:7
ChemMedChem ; 15, Heft 22 (2020), 2157-2163 (gesamt 7)
- Creator
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Maccallini, Cristina
Marinelli, Lisa
Indorf, Patrick
Cacciatore, Ivana
Fantacuzzi, Marialuigia
Clement, Bernd
Di Stefano, Antonio
Amoroso, Rosa
- DOI
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10.1002/cmdc.202000349
- URN
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urn:nbn:de:101:1-2022062512094668673877
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:21 AM CEST
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Associated
- Maccallini, Cristina
- Marinelli, Lisa
- Indorf, Patrick
- Cacciatore, Ivana
- Fantacuzzi, Marialuigia
- Clement, Bernd
- Di Stefano, Antonio
- Amoroso, Rosa
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A Phosphoramidate Prodrug Platform: One‐Pot Amine Functionalization of Kinase Inhibitors with Oligoethylene Glycol for Improved Water‐Solubility
Development and Pharmacokinetic Evaluation of Two Parenteral Formulations of Albendazole Using Prodrug and Cosolvent Approaches
Zap‐Pano: a Photocaged Prodrug of the KDAC Inhibitor Panobinostat
Cephalosporin Prodrug Inhibitors Overcome Metallo‐β‐Lactamase Driven Antibiotic Resistance
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