BIOMAT Database Logo BIOMAT Database Logo

3-{2-[Bis-(4-fluorophenyl)methoxy]ethyl}-6-substituted-3,6-diazabicyclo[3.1.1]heptanes as novel potent dopamine uptake inhibitors. 2007

Giovanni Loriga, and Stefania Ruiu, and Ilaria Manca, and Gabriele Murineddu, and Christian Dessi, and Luca Pani, and Gérard A Pinna
Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, via F. Muroni 23/A, I-07100 Sassari, Italy.

A series of analogues 2a-i related to 3-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-8-(1H-indol-2-ylmethyl)-3,8-diazabicyclo[3.2.1]octane (1) in which the 3,8-diazabicyclo[3.2.1]octane core was replaced by 3,6-diazabicyclo[3.1.1]heptane ring system has been synthesized and evaluated for their ability to inhibit DA reuptake into striatal nerve endings (synaptosomes). Biological data showed that compound 2a, the closest analogue of lead 1, possessed an increased reuptake inhibition activity over 1 (2a, K(i)=5.5 nM). Replacement of the indole ring with bioisosteric aromatic rings--benzothiophene (2b), benzofurane (2c), or indene (2d)--resulted, with the exception of 2d, in a double digit nanomolar activity. Changing the indenyl moiety of 2d with simplified aryl groups led to compounds 2e-h which displayed a similar or slightly decreased activity with respect to the ground term. Naphthalene derivative (2i) demonstrated a weaker activity than aromatic analogues.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008297 Male Males
D006536 Heptanes Seven-carbon alkanes with the formula C7H16. Heptane,Isoheptane,Isoheptanes
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001681 Biological Assay A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. Bioassay,Assay, Biological,Assays, Biological,Biologic Assay,Biologic Assays,Assay, Biologic,Assays, Biologic,Bioassays,Biological Assays
D013574 Synaptosomes Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. Synaptosome
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018765 Dopamine Uptake Inhibitors Drugs that block the transport of DOPAMINE into axon terminals or into storage vesicles within terminals. Most of the ADRENERGIC UPTAKE INHIBITORS also inhibit dopamine uptake. Dopamine Reuptake Inhibitors,Inhibitors, Dopamine Reuptake,Inhibitors, Dopamine Uptake,Reuptake Inhibitors, Dopamine,Uptake Inhibitors, Dopamine
D019086 Bridged Bicyclo Compounds, Heterocyclic Heterocyclic compounds that contain two rings that share two non-adjacent atoms in common. Bicyclo Compounds, Heterocyclic,Heterocyclic Cpds, Bicyclic,Bicyclic Heterocyclic Compounds,Heterocyclic Bicyclo Compounds,Bicyclic Heterocyclic Cpds,Heterocyclic Compounds, Bicyclic

Related Publications

Giovanni Loriga, and Stefania Ruiu, and Ilaria Manca, and Gabriele Murineddu, and Christian Dessi, and Luca Pani, and Gérard A Pinna
Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors.
February 2006, Bioorganic & medicinal chemistry,
Giovanni Loriga, and Stefania Ruiu, and Ilaria Manca, and Gabriele Murineddu, and Christian Dessi, and Luca Pani, and Gérard A Pinna
Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for neuronal nicotinic acetylcholine receptors.
December 2008, Bioorganic & medicinal chemistry letters,
Giovanni Loriga, and Stefania Ruiu, and Ilaria Manca, and Gabriele Murineddu, and Christian Dessi, and Luca Pani, and Gérard A Pinna
Design, synthesis, and biological evaluation of novel non-piperazine analogues of 1-[2-(diphenylmethoxy)ethyl]- and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines as dopamine transporter inhibitors.
September 1999, Journal of medicinal chemistry,
Giovanni Loriga, and Stefania Ruiu, and Ilaria Manca, and Gabriele Murineddu, and Christian Dessi, and Luca Pani, and Gérard A Pinna
Novel N-substituted 3 alpha-[bis(4'-fluorophenyl)methoxy]tropane analogues: selective ligands for the dopamine transporter.
December 1997, Journal of medicinal chemistry,
Giovanni Loriga, and Stefania Ruiu, and Ilaria Manca, and Gabriele Murineddu, and Christian Dessi, and Luca Pani, and Gérard A Pinna
Novel N-aryl nicotinamide derivatives: Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors.
October 2019, European journal of medicinal chemistry,
Giovanni Loriga, and Stefania Ruiu, and Ilaria Manca, and Gabriele Murineddu, and Christian Dessi, and Luca Pani, and Gérard A Pinna
Heteroaromatic analogs of 1-[2-(diphenylmethoxy)ethyl]- and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909) as high-affinity dopamine reuptake inhibitors.
February 1997, Journal of medicinal chemistry,
Giovanni Loriga, and Stefania Ruiu, and Ilaria Manca, and Gabriele Murineddu, and Christian Dessi, and Luca Pani, and Gérard A Pinna
[Pharmacological effects of the novel dopamine uptake inhibitor 1-[2-[bis(4-fluorophenyl)-methoxy]ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride (I-893) on the central nervous system].
August 1991, Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
Giovanni Loriga, and Stefania Ruiu, and Ilaria Manca, and Gabriele Murineddu, and Christian Dessi, and Luca Pani, and Gérard A Pinna
Kinetic mechanism of dopamine transporter interaction with 1-(2-(bis-(4-fluorophenyl)methoxy)ethyl)-4-(3-phenylpropyl)piperazine (GBR 12909).
December 2008, Neurochemistry international,
Giovanni Loriga, and Stefania Ruiu, and Ilaria Manca, and Gabriele Murineddu, and Christian Dessi, and Luca Pani, and Gérard A Pinna
Development of novel, potent, and selective dopamine reuptake inhibitors through alteration of the piperazine ring of 1-[2-(diphenylmethoxy)ethyl]-and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909).
November 1996, Journal of medicinal chemistry,
Giovanni Loriga, and Stefania Ruiu, and Ilaria Manca, and Gabriele Murineddu, and Christian Dessi, and Luca Pani, and Gérard A Pinna
Novel 4'-substituted and 4',4"-disubstituted 3 alpha-(diphenylmethoxy)tropane analogs as potent and selective dopamine uptake inhibitors.
September 1995, Journal of medicinal chemistry,
Copied contents to your clipboard!