Publications (43) View all
-
Article: Potent and selective tariquidar bioisosters as potential PET radiotracers for imaging P-gp.
[show abstract] [hide abstract]
ABSTRACT: Compounds 8a-d have been designed as bioisosters of tariquidar for imaging P-gp expression and density by PET. The results displayed that compounds 8b and 8d could be considered potential P-gp/BCRP ligands suitable as (11)C and (18)F radiotracers, respectively.Bioorganic & medicinal chemistry letters 01/2013; · 2.65 Impact Factor -
Article: Naphthalenyl derivatives for hitting P-gp/MRP1/BCRP transporters.
[show abstract] [hide abstract]
ABSTRACT: Substituted naphthalenyl derivatives bearing oxazole, or thiazole or furyl heteronuclei have been carried out as bioisosters of aryl-oxazoles and -thiazoles derivatives previously reported in order to investigate the role of the hindrance on the activity towards P-gp/BCRP/and MRP1 transporters. In addition, the role of naphthalenyl group to modulate P-gp intrinsic activity of these compounds was ascertained. The results demonstrated that all naphthalenyl derivatives displayed comparable P-gp activity with respect to lead compounds previously characterized in our SAR studies but were less active towards BCRP and MRP1 pumps. In terms of intrinsic activity, the replacement of aryl with naphthalenyl moiety led to P-gp inhibitors, unambiguous or ambiguous substrates on the base of the heteronucleus and the substituent on the naphthalenyl fragment. Indeed, oxazole derivatives were: inhibitors (R=H, F, OH), unambiguous substrates (R=OCH(3)), or ambiguous substrate (R=Br); thiazole derivatives were: unambiguous substrates (R=OCH(3), Br), or ambiguous substrates (R=H, F). Finally furyl derivatives were ambiguous substrates.Bioorganic & medicinal chemistry 12/2012; · 2.82 Impact Factor -
Article: Investigations on the 1-(2-biphenyl)piperazine motif: identification of new potent and selective ligands for the serotonin(7) (5-HT(7)) receptor with agonist or antagonist action in vitro or ex vivo.
[show abstract] [hide abstract]
ABSTRACT: Here we report the design, synthesis, and 5-HT(7) receptor affinity of a set of 1-(3-biphenyl)- and 1-(2-biphenyl)piperazines. The effect on 5-HT(7) affinity of various substituents on the second (distal) phenyl ring was analyzed. Several compounds showed 5-HT(7) affinities in the nanomolar range and >100-fold selectivity over 5-HT(1A) and adrenergic α(1) receptors. 1-[2-(4-Methoxyphenyl)phenyl]piperazine (9a) showed 5-HT(7) agonist properties in a guinea pig ileum assay but blocked 5-HT-mediated cAMP accumulation in 5-HT(7)-expressing HeLa cells.Journal of Medicinal Chemistry 06/2012; 55(14):6375-80. · 4.80 Impact Factor -
Article: A benzopyrane derivative as a P-glycoprotein stimulator: a potential agent to decrease β-amyloid accumulation in Alzheimer's disease.
[show abstract] [hide abstract]
ABSTRACT: A simulating interaction: The P-glycoprotein (P-gp) ligand 13 displays high P-gp interacting activity (EC(50) =2.90 μM) and selectivity in tumor cell lines. Here, this promising compound was further evaluated ex vivo in an everted gut sac assay and found to behave as a P-gp stimulator, making this agent a potential lead for the development of new therapeutics to treat Alzheimer's disease.ChemMedChem 12/2011; 7(3):391-5. · 3.15 Impact Factor -
Article: Synthesis and binding assays of novel 3,3-dimethylpiperidine derivatives with various lipophilicities as σ₁ receptor ligands.
[show abstract] [hide abstract]
ABSTRACT: Starting from two carbocyclic analogs, a series of 3,3-dimethylpiperidine derivatives was prepared and tested in radioligand binding assays at σ(1) and σ(2) receptors, and at Δ(8)-Δ(7) sterol isomerase (SI) site. The novel compounds mostly bear heterocyclic rings or bicyclic nucleus of differing lipophilicities. Compounds 18a and 19a,b demonstrated the highest σ(1) affinity (K(i)=0.14-0.38 nM) with a good selectivity versus σ(2) binding. Among them, 18a had the lowest ClogD value (3.01) and only 19b was selective versus SI too. Generally, it was observed that more planar and hydrophilic heteronuclei conferred a decrease in affinity for both σ receptor subtypes.Bioorganic & medicinal chemistry 10/2011; 19(24):7612-22. · 2.82 Impact Factor
