Battistina Asproni - Academia.edu (original) (raw)
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Papers by Battistina Asproni
ChemMedChem, 2015
d] Prof. A. Sparatore Dipartimento di Scienze Farmaceutiche "P. Pratesi" Università degli Studi d... more d] Prof. A. Sparatore Dipartimento di Scienze Farmaceutiche "P. Pratesi" Università degli Studi di Milano, V. Mangiagalli 25, 20133 Milano (Italy) ChemMedChem 0000, 00, 0 -0
Journal of medicinal chemistry, Jan 7, 2005
A series of new 1,2-diphenylimidazole derivatives (1a-x) were synthesized and evaluated for their... more A series of new 1,2-diphenylimidazole derivatives (1a-x) were synthesized and evaluated for their ability to potentiate gamma-aminobutyric acid (GABA)-evoked currents in Xenopus laevis oocytes expressing recombinant human GABA(A) receptors. Many of these compounds enhanced GABA action with potencies (EC(50) = 0.19-19 muM) and efficacies (maximal efficacies of up to 640%) similar to or greater than those of anesthetics such as etomidate, propofol, and alphaxalone. Structure-activity relationship analysis revealed that the presence of an ester moiety in the imidazole ring was required for full agonist properties, while modifications made in the phenyl rings affected potency and efficacy, with ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate showing the highest potency. These compounds potentiated the [(3)H]GABA binding to rat brain membranes, suggesting a site of interaction different from that of GABA. As for etomidate, mutation of asparagine-265 in the beta2 ...
Molecules, 2009
Designed as a new group of tricyclic molecules containing the thienocycloheptapyridazinone ring s... more Designed as a new group of tricyclic molecules containing the thienocycloheptapyridazinone ring system, a number of 2N-substituted-hexahydrothienocycloheptapyridazinone derivatives were synthesized and their biological activity evaluated. Among the synthesized compounds, derivatives 7d and 7h were found to possess cytotoxic activity against non-small cell lung cancer and central nervous system cancer cell lines, respectively.
Medicinal Chemistry, 2006
A new series of 8-halogen-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acids was prepa... more A new series of 8-halogen-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acids was prepared and tested for aldose reductase (ALR2) inhibitory activities. These compounds showed significant inhibitory activity against bovine lens ALR2, with the best compound 2e showing an IC(50) value of 31.4 microM. The presence of the C8-substituents here studied (Cl, Br) on the thienocinnolinone scaffold caused a decrease of the inhibitory potency by a factor of about 4 with respect to the unsubstituted parent compound, while the presence of a C8-methyl group, considered in a previous paper decreased the activity by a factor of about 2. Moreover, the length of the N2 alkanoic chain influences strongly the enzyme inhibitory activity. While most of the carboxylic acids ALR2 inhibitors are acetic acid derivatives, in the case of thienocinnolinone compounds, homologues higher than acetic acids showed to be more active.
![Research paper thumbnail of Synthesis and Pharmacological Evaluation of 1-[(1,2-Diphenyl-1 H -4-imidazolyl)methyl]-4-phenylpiperazines with Clozapine-Like Mixed Activities at Dopamine D 2 , Serotonin, and GABA A Receptors](https://attachments.academia-assets.com/45833785/thumbnails/1.jpg)
](Journal of Medicinal Chemistry, 2002
A series of phthalimide derivatives were synthesized and evaluated for their analgesic and invitr... more A series of phthalimide derivatives were synthesized and evaluated for their analgesic and invitro antiinflammatory activity. The target compounds were obtained by condensation of N-hydroxymethylphthalimide with the substituted thiadiazole. The structures of the synthesized derivatives were confirmed by means of IR, 1 H-NMR spectral data. The analgesic activity was determined by acetic acid induced writhings in mice and Invitro antiinflammatory activity was evaluated using thermally induced protein denaturation technique. The results revealed the importance of the combination of thiadiazole and phthalimide moieties as a promising analgesic and antiinflammatory candidate.
European Journal of Medicinal Chemistry, 2013
Considering the interesting pharmacological profile of the delta (δ) selective opioid agonist com... more Considering the interesting pharmacological profile of the delta (δ) selective opioid agonist compound SNC-80, conformationally constrained analogs containing two diazatricyclodecane ring systems in place of dimethylpiperazine core motif were synthesized. The compounds showed subnanomolar or low nanomolar δ opioid receptor binding affinity. Depending upon the substituents on the diazatricyclodecane ring, these compounds displayed varying selectivity for δ opioid receptor over μ and κ receptors. Amongst the novel compounds, 1Aa showed the more interesting biological profile, with higher δ affinity and selectivity compared to SNC-80. The δ receptor agonist profile and antinociceptive activity of 1Aa were confirmed using ex-vivo (isolated mouse vas deferens) and in vivo (tail flick) assays.
Contact Dermatitis, 2001
A 33-year-old woman, with diabetes mellitus, developed acute eczema on the abdomen at contact poi... more A 33-year-old woman, with diabetes mellitus, developed acute eczema on the abdomen at contact points with the catheter of a pump infusion set that she had been using for 1 year (Set Per Microinfusione A , Pharma-Plast, Denmark). She gave a previous history of allergy to metals only.
![Research paper thumbnail of Synthesis and SAR study of new phenylimidazole-pyrazolo[1,5-c]quinazolines as potent phosphodiesterase 10A inhibitors](https://attachments.academia-assets.com/45859715/thumbnails/1.jpg)
](Bioorganic & Medicinal Chemistry, 2011
A series of phenylimidazole-pyrazolo[1,5-c]quinazolines 1a-q was designed, synthesized and charac... more A series of phenylimidazole-pyrazolo[1,5-c]quinazolines 1a-q was designed, synthesized and characterised as a novel class of potent phophodiesterase 10A (PDE10A) inhibitors. In this series, 2,9-dimethyl-5-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethyl)pyrazolo[1,5-c]quinazoline (1q) showed the highest affinity for PDE10A enzyme (IC 50 = 16 nM).
![Research paper thumbnail of Tricyclic pyrazoles. Part 6. Benzofuro[3,2-c]pyrazole: A versatile architecture for CB2 selective ligands](https://attachments.academia-assets.com/45859730/thumbnails/1.jpg)
](European Journal of Medicinal Chemistry, 2014
A new series of 1H-benzofuro[3,2-c]pyrazole-3-carboxamides was synthesized. The novel compounds (... more A new series of 1H-benzofuro[3,2-c]pyrazole-3-carboxamides was synthesized. The novel compounds (15e24) were evaluated for their affinity to CB 2 and CB 1 cannabinoid receptors. The synthesis of the title compounds takes advantage of the acid-catalysed thermal cyclization of bicyclic hydrazone ethyl 2-(2-(2,4-dichlorophenyl)hydrazono)-2-(6-methyl-3-oxo-2,3-dihydrobenzofuran-2-yl)acetate to tricyclic ethyl 1-(2,4-dichlorophenyl)-6-methyl-1H-benzofuro[3,2-c]pyrazol-3-carboxylate.
ChemMedChem, 2015
d] Prof. A. Sparatore Dipartimento di Scienze Farmaceutiche "P. Pratesi" Università degli Studi d... more d] Prof. A. Sparatore Dipartimento di Scienze Farmaceutiche "P. Pratesi" Università degli Studi di Milano, V. Mangiagalli 25, 20133 Milano (Italy) ChemMedChem 0000, 00, 0 -0
Journal of medicinal chemistry, Jan 7, 2005
A series of new 1,2-diphenylimidazole derivatives (1a-x) were synthesized and evaluated for their... more A series of new 1,2-diphenylimidazole derivatives (1a-x) were synthesized and evaluated for their ability to potentiate gamma-aminobutyric acid (GABA)-evoked currents in Xenopus laevis oocytes expressing recombinant human GABA(A) receptors. Many of these compounds enhanced GABA action with potencies (EC(50) = 0.19-19 muM) and efficacies (maximal efficacies of up to 640%) similar to or greater than those of anesthetics such as etomidate, propofol, and alphaxalone. Structure-activity relationship analysis revealed that the presence of an ester moiety in the imidazole ring was required for full agonist properties, while modifications made in the phenyl rings affected potency and efficacy, with ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate showing the highest potency. These compounds potentiated the [(3)H]GABA binding to rat brain membranes, suggesting a site of interaction different from that of GABA. As for etomidate, mutation of asparagine-265 in the beta2 ...
Molecules, 2009
Designed as a new group of tricyclic molecules containing the thienocycloheptapyridazinone ring s... more Designed as a new group of tricyclic molecules containing the thienocycloheptapyridazinone ring system, a number of 2N-substituted-hexahydrothienocycloheptapyridazinone derivatives were synthesized and their biological activity evaluated. Among the synthesized compounds, derivatives 7d and 7h were found to possess cytotoxic activity against non-small cell lung cancer and central nervous system cancer cell lines, respectively.
Medicinal Chemistry, 2006
A new series of 8-halogen-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acids was prepa... more A new series of 8-halogen-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acids was prepared and tested for aldose reductase (ALR2) inhibitory activities. These compounds showed significant inhibitory activity against bovine lens ALR2, with the best compound 2e showing an IC(50) value of 31.4 microM. The presence of the C8-substituents here studied (Cl, Br) on the thienocinnolinone scaffold caused a decrease of the inhibitory potency by a factor of about 4 with respect to the unsubstituted parent compound, while the presence of a C8-methyl group, considered in a previous paper decreased the activity by a factor of about 2. Moreover, the length of the N2 alkanoic chain influences strongly the enzyme inhibitory activity. While most of the carboxylic acids ALR2 inhibitors are acetic acid derivatives, in the case of thienocinnolinone compounds, homologues higher than acetic acids showed to be more active.
Journal of Medicinal Chemistry, 2002
A series of phthalimide derivatives were synthesized and evaluated for their analgesic and invitr... more A series of phthalimide derivatives were synthesized and evaluated for their analgesic and invitro antiinflammatory activity. The target compounds were obtained by condensation of N-hydroxymethylphthalimide with the substituted thiadiazole. The structures of the synthesized derivatives were confirmed by means of IR, 1 H-NMR spectral data. The analgesic activity was determined by acetic acid induced writhings in mice and Invitro antiinflammatory activity was evaluated using thermally induced protein denaturation technique. The results revealed the importance of the combination of thiadiazole and phthalimide moieties as a promising analgesic and antiinflammatory candidate.
European Journal of Medicinal Chemistry, 2013
Considering the interesting pharmacological profile of the delta (δ) selective opioid agonist com... more Considering the interesting pharmacological profile of the delta (δ) selective opioid agonist compound SNC-80, conformationally constrained analogs containing two diazatricyclodecane ring systems in place of dimethylpiperazine core motif were synthesized. The compounds showed subnanomolar or low nanomolar δ opioid receptor binding affinity. Depending upon the substituents on the diazatricyclodecane ring, these compounds displayed varying selectivity for δ opioid receptor over μ and κ receptors. Amongst the novel compounds, 1Aa showed the more interesting biological profile, with higher δ affinity and selectivity compared to SNC-80. The δ receptor agonist profile and antinociceptive activity of 1Aa were confirmed using ex-vivo (isolated mouse vas deferens) and in vivo (tail flick) assays.
Contact Dermatitis, 2001
A 33-year-old woman, with diabetes mellitus, developed acute eczema on the abdomen at contact poi... more A 33-year-old woman, with diabetes mellitus, developed acute eczema on the abdomen at contact points with the catheter of a pump infusion set that she had been using for 1 year (Set Per Microinfusione A , Pharma-Plast, Denmark). She gave a previous history of allergy to metals only.
Bioorganic & Medicinal Chemistry, 2011
A series of phenylimidazole-pyrazolo[1,5-c]quinazolines 1a-q was designed, synthesized and charac... more A series of phenylimidazole-pyrazolo[1,5-c]quinazolines 1a-q was designed, synthesized and characterised as a novel class of potent phophodiesterase 10A (PDE10A) inhibitors. In this series, 2,9-dimethyl-5-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethyl)pyrazolo[1,5-c]quinazoline (1q) showed the highest affinity for PDE10A enzyme (IC 50 = 16 nM).
European Journal of Medicinal Chemistry, 2014
A new series of 1H-benzofuro[3,2-c]pyrazole-3-carboxamides was synthesized. The novel compounds (... more A new series of 1H-benzofuro[3,2-c]pyrazole-3-carboxamides was synthesized. The novel compounds (15e24) were evaluated for their affinity to CB 2 and CB 1 cannabinoid receptors. The synthesis of the title compounds takes advantage of the acid-catalysed thermal cyclization of bicyclic hydrazone ethyl 2-(2-(2,4-dichlorophenyl)hydrazono)-2-(6-methyl-3-oxo-2,3-dihydrobenzofuran-2-yl)acetate to tricyclic ethyl 1-(2,4-dichlorophenyl)-6-methyl-1H-benzofuro[3,2-c]pyrazol-3-carboxylate.