title: 3-Aza-6,8-dioxabicyclo[3.2.1]octanes as new enantiopure heteroatom-rich tropane-like ligands of human dopamine transporter.
abstract: CNS diseases such as Parkinson, schizophrenia, and attention deficit hyperactivity disorder (ADHD) are characterized by a significant alteration of dopamine transporter (DAT) density. Thus, the development of compounds that are able to selectively interact with DAT is of great interest. Herein we describe the design and synthesis of a new set of 3-aza-6,8-dioxabicyclo[3.2.1]octanes having a tropane-like structure with additional heteroatoms at positions 3 and 6. The compounds were evaluated for their in vitro receptor binding properties toward human dopamine (hDAT) and serotonin (hSERT) transporters using [3H]WIN35,428 and [3H]citalopram as specific radioligands, respectively. Biological assays revealed that some compounds having the N-3 atom substituted with aryl groups possess significant affinity and selectivity for monoamine transporters, and in particular, compound 5d displayed an IC50 of 21 nM toward DAT, and a good selectivity toward SERT (IC50=1042 nM). These results suggest that 3-aryl-3-aza-6,8-dioxabicyclo[3.2.1]octanes may represent a new class of DAT ligands.
authors: Dipartimento di Fisiopatologia Clinica, Unità di Medicina Nucleare, Università degli Studi di Firenze, Viale Pieraccini 6, I-50134 Firenze, Italy.
authors: Nicoletta
authors: N
authors: Cini
authors: Elisa
authors: E
authors: Danieli
authors: Gloria
authors: G
authors: Menchi
authors: Andrea
authors: A
authors: Trabocchi
authors: Anna
authors: A
authors: Bottoncetti
authors: Silvia
authors: S
authors: Raspanti
authors: Alberto
authors: A
authors: Pupi
authors: Antonio
authors: A
authors: Guarna