Synthesis of epibatidine isomers: endo-5- and 6- (6′-chloro-3′-pyridyl-2-azabicyclo[2.2.1]heptanes

Synthesis of the title compounds is described; detailed NMR data are provided in support of the proposed stereostructures. The 5- and 6-endo-compounds show high selectivity for α4β2 versus α7 nAChR subtypes; in contrast, the exo-stereoisomers show comparatively weak affinity at both subtypes.

[1]  M. Lebedev,et al.  A NOVEL EFFICIENT SYNTHESIS OF HETEROARYL SUBSTITUTED ALPHA ,BETA -UNSATURATED TRIFLUOROMETHYL KETONES , 2000 .

[2]  D. Bertrand,et al.  A new look at the neuronal nicotinic acetylcholine receptor pharmacophore. , 2000, European journal of pharmacology.

[3]  M. Williams,et al.  Neuronal nicotinic acetylcholine receptors as novel drug targets. , 2000, The Journal of pharmacology and experimental therapeutics.

[4]  I. Pettersson,et al.  Improving the nicotinic pharmacophore with a series of (Isoxazole)methylene-1-azacyclic compounds: synthesis, structure-activity relationship, and molecular modeling. , 1999, Journal of medicinal chemistry.

[5]  P. Cullis,et al.  2-Azabicyclo[2.2.1]hept-5-en-3-one epoxide: A versatile intermediate for the synthesis of cyclopentyl carbocyclic 2-deoxy-, 3-deoxy- & ara- ribonucleoside analogues , 1999 .

[6]  P. Helquist,et al.  Palladium(II)-Catalyzed 1,4-Oxidation of 2-Aryl-1,3-cyclohexadienes. Application to the Synthesis of (+/-)-Epibatidine and Analogues. , 1999, The Journal of organic chemistry.

[7]  W. S. Caldwell,et al.  The heterocyclic substituted pyridine derivative (+/-)-2-(-3-pyridinyl)-1-azabicyclo[2.2.2]octane (RJR-2429): a selective ligand at nicotinic acetylcholine receptors. , 1998, The Journal of pharmacology and experimental therapeutics.

[8]  A. Sahoo,et al.  [3 + 2] Cycloaddition of Nonstabilized Azomethine Ylides. 7. Stereoselective Synthesis of Epibatidine and Analogues(,). , 1998, The Journal of organic chemistry.

[9]  J K Lynch,et al.  Neuronal nicotinic acetylcholine receptors as targets for drug discovery. , 1997, Journal of medicinal chemistry.

[10]  J. Malpass,et al.  Synthesis of exo- and endo-7,8-epoxyhomotropanes , 1996 .

[11]  Donglu Bai,et al.  Synthesis of (+/-)-Epibatidine and Its Analogues. , 1996, The Journal of organic chemistry.

[12]  J. Malpass,et al.  Synthesis of epibatidine homologues: Homoepibatidine and bis-homoepibatidine , 1996 .

[13]  R. Ball,et al.  Total Synthesis and Determination of the Absolute Configuration of Epibatidine , 1994 .

[14]  P. Leff,et al.  Further concerns over Cheng-Prusoff analysis. , 1993, Trends in pharmacological sciences.

[15]  J. Malpass,et al.  NMR studies of n-methyl derivatives of the 2-azabicyclo-[2.2.1]heptyl and -[2.2.2]octyl ring systems; kinetic protonation in determination of Invertomer preferences , 1993 .

[16]  D J Triggle,et al.  Synthesis and muscarinic receptor activity of ester derivatives of 2-substituted 2-azabicyclo[2.2.1]heptan-5-ol and -6-ol. , 1992, Journal of medicinal chemistry.

[17]  S. Larsen,et al.  Aza Diels-Alder reactions in aqueous solution: cyclocondensation of dienes with simple iminium salts generated under Mannich conditions , 1985 .