Ionotropic glutamate receptor (iGluR) modulators, specially AMPA receptor antagonists, are potential tools for numerous therapeutic applications in neurological disorders, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, epilepsy, chronic pain, and neuropathology ensuing from cerebral ischemia or cardiac arrest. In this work, the synthesis and binding affinities at the Gly/NMDA, AMPA, and kainic acid (KA) receptors of a new series of 1,2,4-benzothiadiazine- 1,1-dioxide derivatives are reported. The results show that 1,2,4-benzothiadiazine-1,1-dioxide is a new scaffold for obtaining iGluR ligands. Moreover, this work has led us to the 7-(3-formylpyrrol-1-yl)-6- trifluoromethyl substituted compound 7, which displays the highest AMPA receptor affinity and high selectivity versus the Gly/NMDA (90-fold) and KA (46-fold) receptors.

1,2,4-Benzothiadiazine-1,1-dioxide Derivatives as Ionotropic Glutamate Receptor Ligands: Synthesis and Structure–Activity Relationships / Flavia Varano; Daniela Catarzi; Vittoria Colotta; Lucia Squarcialupi; Rosanna Matucci. - In: ARCHIV DER PHARMAZIE. - ISSN 0365-6233. - ELETTRONICO. - (2014), pp. 777-785. [10.1002/ardp.201400192]

1,2,4-Benzothiadiazine-1,1-dioxide Derivatives as Ionotropic Glutamate Receptor Ligands: Synthesis and Structure–Activity Relationships

VARANO, FLAVIA;CATARZI, DANIELA;COLOTTA, VITTORIA;SQUARCIALUPI, LUCIA;MATUCCI, ROSANNA
2014

Abstract

Ionotropic glutamate receptor (iGluR) modulators, specially AMPA receptor antagonists, are potential tools for numerous therapeutic applications in neurological disorders, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, epilepsy, chronic pain, and neuropathology ensuing from cerebral ischemia or cardiac arrest. In this work, the synthesis and binding affinities at the Gly/NMDA, AMPA, and kainic acid (KA) receptors of a new series of 1,2,4-benzothiadiazine- 1,1-dioxide derivatives are reported. The results show that 1,2,4-benzothiadiazine-1,1-dioxide is a new scaffold for obtaining iGluR ligands. Moreover, this work has led us to the 7-(3-formylpyrrol-1-yl)-6- trifluoromethyl substituted compound 7, which displays the highest AMPA receptor affinity and high selectivity versus the Gly/NMDA (90-fold) and KA (46-fold) receptors.
777
785
Flavia Varano; Daniela Catarzi; Vittoria Colotta; Lucia Squarcialupi; Rosanna Matucci
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/998007
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