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Carla Ghelardini - One of the best experts on this subject based on the ideXlab platform.

  • synthesis in vivo evaluation and molecular modeling studies of new pyrazolo 5 1 c 1 2 4 benzotriazine 5 oxide derivatives identification of a bifunctional hydrogen bond area related to the inverse agonism
    Journal of Medicinal Chemistry, 2009
    Co-Authors: Gabriella Guerrini, G Ciciani, Giovanni Cambi, F Bruni, Silvia Selleri, Chiara Guarino, Fabrizio Melani, Marina Montali, Claudia Martini, Carla Ghelardini
    Abstract:

    A new series of pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 8-alkyloxy-/aryloxy-/arylalkyloxy and 8-aryl-/arylalkylderivatives variously substituted at the 3-position were synthesized and binding studies at the benzodiazepine site on GABA(A) receptor were carried out. The pharmacological profile was identified for compounds 10, 11, 16(+), 16(-), and 17 by considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motility and explorative activity, potential anxiolytic-like effects, mouse learning and Memory Modulation, and finally, ethanol-potentiating action. Compound 17 stands out as the compound that improves mouse Memory processes selectively, safely, and in a statistically significant manner. From a ligand-based pharmacophoric model, we identified a hydrogen bond interaction area HBp-3 near the lipophilic area. This new pharmacophoric model allowed us to identify four structural compound typologies and thus to rationalize the affinity data of all compounds.

  • novel 3 aroylpyrazolo 5 1 c 1 2 4 benzotriazine 5 oxides 8 substituted ligands at gabaa benzodiazepine receptor complex synthesis pharmacological and molecular modeling studies
    Bioorganic & Medicinal Chemistry, 2008
    Co-Authors: Gabriella Guerrini, G Ciciani, Giovanni Cambi, F Bruni, Silvia Selleri, Fabrizio Melani, Marina Montali, Claudia Martini, Carla Ghelardini, Monica Norcini
    Abstract:

    Abstract The synthesis and binding studies of a series of 3-acylpyrazolo[5,1- c ][1,2,4]benzotriazine 5-oxides 8-substituted are reported. High-affinity ligands at benzodiazepine site on GABA A receptor complex (GABA A /BzR complex) were obtained when the 3-aroyl substituent is represented by a five-member heteroaroyl ring (furoyl-, thenoyl-, and pyrroyl-). Moreover the type of heteroaroyl ring at position 3 influences the feature of the substituent at position 8 to obtain high-affinity ligands: a ‘hydrogen-bond acceptor ring’ at position 3 is synergic with an electron donor substituent at position 8, while a ‘hydrogen-bond donor ring’ is synergic with a withdrawing substituent. Compounds 8a , 9b , and 11 were deeply studied in vivo for their pharmacological effects considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motor activity and explorative activity, anxiolytic-like effects, mouse learning and Memory Modulation, and ethanol-potentiating action. To rationalize and qualitatively interpret the GABA A /Bz binding affinities of compounds 8a and 11 , a dynamic molecular modeling study has been performed, with the aim of assessing the preferred geometry of protein–ligand complex.

Gabriella Guerrini - One of the best experts on this subject based on the ideXlab platform.

  • synthesis in vivo evaluation and molecular modeling studies of new pyrazolo 5 1 c 1 2 4 benzotriazine 5 oxide derivatives identification of a bifunctional hydrogen bond area related to the inverse agonism
    Journal of Medicinal Chemistry, 2009
    Co-Authors: Gabriella Guerrini, G Ciciani, Giovanni Cambi, F Bruni, Silvia Selleri, Chiara Guarino, Fabrizio Melani, Marina Montali, Claudia Martini, Carla Ghelardini
    Abstract:

    A new series of pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 8-alkyloxy-/aryloxy-/arylalkyloxy and 8-aryl-/arylalkylderivatives variously substituted at the 3-position were synthesized and binding studies at the benzodiazepine site on GABA(A) receptor were carried out. The pharmacological profile was identified for compounds 10, 11, 16(+), 16(-), and 17 by considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motility and explorative activity, potential anxiolytic-like effects, mouse learning and Memory Modulation, and finally, ethanol-potentiating action. Compound 17 stands out as the compound that improves mouse Memory processes selectively, safely, and in a statistically significant manner. From a ligand-based pharmacophoric model, we identified a hydrogen bond interaction area HBp-3 near the lipophilic area. This new pharmacophoric model allowed us to identify four structural compound typologies and thus to rationalize the affinity data of all compounds.

  • novel 3 aroylpyrazolo 5 1 c 1 2 4 benzotriazine 5 oxides 8 substituted ligands at gabaa benzodiazepine receptor complex synthesis pharmacological and molecular modeling studies
    Bioorganic & Medicinal Chemistry, 2008
    Co-Authors: Gabriella Guerrini, G Ciciani, Giovanni Cambi, F Bruni, Silvia Selleri, Fabrizio Melani, Marina Montali, Claudia Martini, Carla Ghelardini, Monica Norcini
    Abstract:

    Abstract The synthesis and binding studies of a series of 3-acylpyrazolo[5,1- c ][1,2,4]benzotriazine 5-oxides 8-substituted are reported. High-affinity ligands at benzodiazepine site on GABA A receptor complex (GABA A /BzR complex) were obtained when the 3-aroyl substituent is represented by a five-member heteroaroyl ring (furoyl-, thenoyl-, and pyrroyl-). Moreover the type of heteroaroyl ring at position 3 influences the feature of the substituent at position 8 to obtain high-affinity ligands: a ‘hydrogen-bond acceptor ring’ at position 3 is synergic with an electron donor substituent at position 8, while a ‘hydrogen-bond donor ring’ is synergic with a withdrawing substituent. Compounds 8a , 9b , and 11 were deeply studied in vivo for their pharmacological effects considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motor activity and explorative activity, anxiolytic-like effects, mouse learning and Memory Modulation, and ethanol-potentiating action. To rationalize and qualitatively interpret the GABA A /Bz binding affinities of compounds 8a and 11 , a dynamic molecular modeling study has been performed, with the aim of assessing the preferred geometry of protein–ligand complex.

F Bruni - One of the best experts on this subject based on the ideXlab platform.

  • synthesis in vivo evaluation and molecular modeling studies of new pyrazolo 5 1 c 1 2 4 benzotriazine 5 oxide derivatives identification of a bifunctional hydrogen bond area related to the inverse agonism
    Journal of Medicinal Chemistry, 2009
    Co-Authors: Gabriella Guerrini, G Ciciani, Giovanni Cambi, F Bruni, Silvia Selleri, Chiara Guarino, Fabrizio Melani, Marina Montali, Claudia Martini, Carla Ghelardini
    Abstract:

    A new series of pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 8-alkyloxy-/aryloxy-/arylalkyloxy and 8-aryl-/arylalkylderivatives variously substituted at the 3-position were synthesized and binding studies at the benzodiazepine site on GABA(A) receptor were carried out. The pharmacological profile was identified for compounds 10, 11, 16(+), 16(-), and 17 by considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motility and explorative activity, potential anxiolytic-like effects, mouse learning and Memory Modulation, and finally, ethanol-potentiating action. Compound 17 stands out as the compound that improves mouse Memory processes selectively, safely, and in a statistically significant manner. From a ligand-based pharmacophoric model, we identified a hydrogen bond interaction area HBp-3 near the lipophilic area. This new pharmacophoric model allowed us to identify four structural compound typologies and thus to rationalize the affinity data of all compounds.

  • novel 3 aroylpyrazolo 5 1 c 1 2 4 benzotriazine 5 oxides 8 substituted ligands at gabaa benzodiazepine receptor complex synthesis pharmacological and molecular modeling studies
    Bioorganic & Medicinal Chemistry, 2008
    Co-Authors: Gabriella Guerrini, G Ciciani, Giovanni Cambi, F Bruni, Silvia Selleri, Fabrizio Melani, Marina Montali, Claudia Martini, Carla Ghelardini, Monica Norcini
    Abstract:

    Abstract The synthesis and binding studies of a series of 3-acylpyrazolo[5,1- c ][1,2,4]benzotriazine 5-oxides 8-substituted are reported. High-affinity ligands at benzodiazepine site on GABA A receptor complex (GABA A /BzR complex) were obtained when the 3-aroyl substituent is represented by a five-member heteroaroyl ring (furoyl-, thenoyl-, and pyrroyl-). Moreover the type of heteroaroyl ring at position 3 influences the feature of the substituent at position 8 to obtain high-affinity ligands: a ‘hydrogen-bond acceptor ring’ at position 3 is synergic with an electron donor substituent at position 8, while a ‘hydrogen-bond donor ring’ is synergic with a withdrawing substituent. Compounds 8a , 9b , and 11 were deeply studied in vivo for their pharmacological effects considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motor activity and explorative activity, anxiolytic-like effects, mouse learning and Memory Modulation, and ethanol-potentiating action. To rationalize and qualitatively interpret the GABA A /Bz binding affinities of compounds 8a and 11 , a dynamic molecular modeling study has been performed, with the aim of assessing the preferred geometry of protein–ligand complex.

Claudia Martini - One of the best experts on this subject based on the ideXlab platform.

  • synthesis in vivo evaluation and molecular modeling studies of new pyrazolo 5 1 c 1 2 4 benzotriazine 5 oxide derivatives identification of a bifunctional hydrogen bond area related to the inverse agonism
    Journal of Medicinal Chemistry, 2009
    Co-Authors: Gabriella Guerrini, G Ciciani, Giovanni Cambi, F Bruni, Silvia Selleri, Chiara Guarino, Fabrizio Melani, Marina Montali, Claudia Martini, Carla Ghelardini
    Abstract:

    A new series of pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 8-alkyloxy-/aryloxy-/arylalkyloxy and 8-aryl-/arylalkylderivatives variously substituted at the 3-position were synthesized and binding studies at the benzodiazepine site on GABA(A) receptor were carried out. The pharmacological profile was identified for compounds 10, 11, 16(+), 16(-), and 17 by considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motility and explorative activity, potential anxiolytic-like effects, mouse learning and Memory Modulation, and finally, ethanol-potentiating action. Compound 17 stands out as the compound that improves mouse Memory processes selectively, safely, and in a statistically significant manner. From a ligand-based pharmacophoric model, we identified a hydrogen bond interaction area HBp-3 near the lipophilic area. This new pharmacophoric model allowed us to identify four structural compound typologies and thus to rationalize the affinity data of all compounds.

  • novel 3 aroylpyrazolo 5 1 c 1 2 4 benzotriazine 5 oxides 8 substituted ligands at gabaa benzodiazepine receptor complex synthesis pharmacological and molecular modeling studies
    Bioorganic & Medicinal Chemistry, 2008
    Co-Authors: Gabriella Guerrini, G Ciciani, Giovanni Cambi, F Bruni, Silvia Selleri, Fabrizio Melani, Marina Montali, Claudia Martini, Carla Ghelardini, Monica Norcini
    Abstract:

    Abstract The synthesis and binding studies of a series of 3-acylpyrazolo[5,1- c ][1,2,4]benzotriazine 5-oxides 8-substituted are reported. High-affinity ligands at benzodiazepine site on GABA A receptor complex (GABA A /BzR complex) were obtained when the 3-aroyl substituent is represented by a five-member heteroaroyl ring (furoyl-, thenoyl-, and pyrroyl-). Moreover the type of heteroaroyl ring at position 3 influences the feature of the substituent at position 8 to obtain high-affinity ligands: a ‘hydrogen-bond acceptor ring’ at position 3 is synergic with an electron donor substituent at position 8, while a ‘hydrogen-bond donor ring’ is synergic with a withdrawing substituent. Compounds 8a , 9b , and 11 were deeply studied in vivo for their pharmacological effects considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motor activity and explorative activity, anxiolytic-like effects, mouse learning and Memory Modulation, and ethanol-potentiating action. To rationalize and qualitatively interpret the GABA A /Bz binding affinities of compounds 8a and 11 , a dynamic molecular modeling study has been performed, with the aim of assessing the preferred geometry of protein–ligand complex.

Marina Montali - One of the best experts on this subject based on the ideXlab platform.

  • synthesis in vivo evaluation and molecular modeling studies of new pyrazolo 5 1 c 1 2 4 benzotriazine 5 oxide derivatives identification of a bifunctional hydrogen bond area related to the inverse agonism
    Journal of Medicinal Chemistry, 2009
    Co-Authors: Gabriella Guerrini, G Ciciani, Giovanni Cambi, F Bruni, Silvia Selleri, Chiara Guarino, Fabrizio Melani, Marina Montali, Claudia Martini, Carla Ghelardini
    Abstract:

    A new series of pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 8-alkyloxy-/aryloxy-/arylalkyloxy and 8-aryl-/arylalkylderivatives variously substituted at the 3-position were synthesized and binding studies at the benzodiazepine site on GABA(A) receptor were carried out. The pharmacological profile was identified for compounds 10, 11, 16(+), 16(-), and 17 by considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motility and explorative activity, potential anxiolytic-like effects, mouse learning and Memory Modulation, and finally, ethanol-potentiating action. Compound 17 stands out as the compound that improves mouse Memory processes selectively, safely, and in a statistically significant manner. From a ligand-based pharmacophoric model, we identified a hydrogen bond interaction area HBp-3 near the lipophilic area. This new pharmacophoric model allowed us to identify four structural compound typologies and thus to rationalize the affinity data of all compounds.

  • novel 3 aroylpyrazolo 5 1 c 1 2 4 benzotriazine 5 oxides 8 substituted ligands at gabaa benzodiazepine receptor complex synthesis pharmacological and molecular modeling studies
    Bioorganic & Medicinal Chemistry, 2008
    Co-Authors: Gabriella Guerrini, G Ciciani, Giovanni Cambi, F Bruni, Silvia Selleri, Fabrizio Melani, Marina Montali, Claudia Martini, Carla Ghelardini, Monica Norcini
    Abstract:

    Abstract The synthesis and binding studies of a series of 3-acylpyrazolo[5,1- c ][1,2,4]benzotriazine 5-oxides 8-substituted are reported. High-affinity ligands at benzodiazepine site on GABA A receptor complex (GABA A /BzR complex) were obtained when the 3-aroyl substituent is represented by a five-member heteroaroyl ring (furoyl-, thenoyl-, and pyrroyl-). Moreover the type of heteroaroyl ring at position 3 influences the feature of the substituent at position 8 to obtain high-affinity ligands: a ‘hydrogen-bond acceptor ring’ at position 3 is synergic with an electron donor substituent at position 8, while a ‘hydrogen-bond donor ring’ is synergic with a withdrawing substituent. Compounds 8a , 9b , and 11 were deeply studied in vivo for their pharmacological effects considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motor activity and explorative activity, anxiolytic-like effects, mouse learning and Memory Modulation, and ethanol-potentiating action. To rationalize and qualitatively interpret the GABA A /Bz binding affinities of compounds 8a and 11 , a dynamic molecular modeling study has been performed, with the aim of assessing the preferred geometry of protein–ligand complex.