160732-46-7Relevant academic research and scientific papers
Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2′-substituted 5′-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Epibatidine analogues
Carroll,Liang,Navarro,Brieaddy,Abraham,Damaj,Martin
, p. 2229 - 2237 (2001)
A convenient, high-yield synthesis of 7-tert-butoxycarbonyl-7-azabicyclo[2.2.1]hept-2-ene (5), which involved the addition of tributyltin hydride to 7-tert-butoxycarbonyl-2-p-toluenesulfonyl-7-azabicyclo[2.2.1]hept-2-ene (4) followed by elimination of the tributyltin and p-tolylsulfonyl groups using tetrabutylammonium fluoride was developed. The addition of 2-amino-5-iodopyridine to 5 under reductive Heck conditions provided 7-tert-butoxycarbonyl-2-exo-(2′-amino-5′-pyridinyl)-7-azabicyclo [2.2.1]heptane (6). Compound 6 was the key intermediate used to prepare epibatidine analogues where the 2′-chloro group on the pyridine ring was replaced with a fluorine (1b), bromine (1c), iodine (1d), hydroxy (1e), amino (1f), dimethylamino (1g), trifluoromethanesulfonate (1h), and hydrogen (1i) group. (+)- and (-)-Epibatidine and compounds 1b-d and 1i all possess similar binding affinities at the (α4β2 nAChR receptors labeled by [3H]epibatidine. Compound 1f has affinity similar to nicotine, whereas compounds 1e, 1g, and 1h have much lower affinity. The binding affinity appears to be dependent upon the electronic nature of the substituent. However, other factors are also involved. None of the compounds possesses appreciable affinity for the α7 nAChR labeled by [125I] iodo-MLA. With the exception of 1f and 1g, all the epibatidine analogues are full agonists (tail flick test) in producing antinociception after intrathecal injection in mice.
First intermolecular Pauson-Khand reaction of 7-azanorbornenes. Control of the regioselectivity by the effect of the substituents attached to the olefinic partner
Arjona, Odón,Csák?, Aurelio G.,Medel, Rocío,Plumet, Joaquín
, p. 3085 - 3087 (2001)
High regioselectivity in the intermolecular Pauson-Khand reaction of 7-azanorborn-5-enes has been found by using 5-bromo-2-endo-tosyl derivatives as the olefinic partner.
On the electronic effects of OH groups. Synthesis and investigation of tetrahydroxylated azabicycloheptanes
Gregersen, Anette,Pedersen, Christian Marcus,Jensen, Henrik Helligso,Bols, Mikael
, p. 1514 - 1519 (2007/10/03)
Two stereoisomeric 2,3,5,6-tetrahydroxyazabicyclo[2.2.1]heptanes were synthesised and their base strengths determined. The 2,3,5,6-exo-isomer 1 and the 2,3-exo-5,6-endo-isomer 2 were prepared from the Diels-Aldcr adduct of Boc-pyrrole and tosylacetylene b
Compounds and methods for promoting smoking cessation
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, (2008/06/13)
Compounds and methods for promoting smoking cessation. The compounds may be used to treat a variety of other conditions and disease states.
Synthesis of a fluorine-18 labeled derivative of epibatidine for in vivo nicotinic acetylcholine receptor PET imaging
Dolci, Lilian,Dolle, Frederic,Valette, Heric,Vaufrey, Francoise,Fuseau, Chantal,Bottlaender, Michel,Crouzel, Christian
, p. 467 - 479 (2007/10/03)
Epibatidine (exo-2-(2'-chloro-5'-pyridyl)-7-azabicyclo[2.2.1]heptane), a natural compound isolated from the skin of the Ecuadorian poison frog Epipedobates tricolor, is the most potent nicotinic acetylcholine receptor (nAChR) agonist reported to date. In order to visualize and quantify in vivo these receptors in human brain using Positron Emission Tomography (PET), [18F]norchlorofluoroepibatidine (exo-2-(2'-[18F]fluoro-5'-pyridyl)-7-azabicyclo[2.2.1]heptane), a fluorine-18 (t(1/2): 110min) radiolabeled derivative of epibatidine has been designed. The corresponding 2'-bromo-, 2'-iodo- and 2'-nitro exo-2-(5'-pyridyl)-7-azabicyclo[2.2.1]heptane analogues as labeling precursors, as well as norchlorofluoroepibatidine as a reference compound have been synthesized by reductive, stereoselective, palladium-catalyzed Heck-type coupling between an N-Boc protected azanorbornene and the corresponding halopyridine. [18F]Norchlorofluoroepibatidine has been radiolabeled with fluorine-18 by nucleophilic aromatic substitution from the corresponding Boc-protected halo- and nitro precursors using [18F]FK-K222 complex in DMSO by conventional heating (at 150-180°C for 10min) or microwave activations (at 100 Watt, for 1 to 2.5min), followed by TFA-removal of the protective group. Typically, using the microwave activation procedure, 60-80mCi (2.22-2.96 GBq) of pure [18F]norchlorofluoroepibatidine could be obtained in less than 2h (110-115min) from the bromo labeling precursor, with specific radioactivities of 1.5-2.5Ci/μmol (55.5-92.5GBq/μmol) calculated for End of Bombardment. The preliminary PET experiments in baboon (Papio papio) with [18F]norchlorofluoroepibatidine show a high uptake and a rapid accumulation of the radiotracer into the brain within 30min. In the thalamus, a nAChR rich area, uptake of radioactivity reached a maximum at 40min (10% I.D./100mL tissue). The ratio of radioactivity thalamus/cerebellum (the latter being a nAChR poor area) was 2 at 40min and increased with time, up to 4.3 at 160min. Its specific regiodistribution and its high ratio of specific-to-nonspecific binding confirm the ideal profile of [18F]norchlorofluoroepibatidine as a suitable radioligand for PET imaging of nAChRs in the brain. Copyright (C) 1999 Elsevier Science Ltd.
The total synthesis of the analgesic alkaloid epibatidine
Giblin, Gerard M. P.,Jones, Clifford D.,Simpkins, Nigel S.
, p. 3689 - 3697 (2007/10/03)
Several synthetic routes to the analgesic alkaloid epibatidine have been explored. Approaches starting from tropinone, involving either ring-cleavage followed by intramolecular aldol reaction, or Favorskii ring-contraction, were not successful. A successf
A concise stereoselective synthesis of epibatidine employing conjugate addition to an alkenyl sulfone intermediate as the key step
Giblin, Gerrard M. P.,Jones, Clifford D.,Simpkins, Nigel S.
, p. 589 - 590 (2007/10/03)
A new synthesis of racemic epibatidine has been achieved, which involves conjugate addition of a metallated 2-methoxypyridine derivative to a suitably protected azabicyclic alkenyl sulfone as the key step.
