7394 Journal of Medicinal Chemistry, 2008, Vol. 51, No. 23
Hansen et al.
(4) Le Nove`re, N.; Changeux, J. P. Molecular evolution of the nicotinic
acetylcholine-receptor. An example of multigene family in excitable
cells. J. Mol. EVol. 1995, 40, 155–172.
(5) Romanelli, M. N.; Gratteri, P.; Guandalini, L.; Martini, E.; Bonaccini,
C.; Gualtieri, F. Central nicotinic receptors: structure, function, ligands,
and therapeutic potential. ChemMedChem 2007, 2, 746–767.
(6) Girod, R.; Barazangi, N.; McGehee, D.; Role, L. W. Facilitation of
glutamatergic neurotransmission by presynaptic nicotinic acetylcholine
receptors. Neuropharmacology 2000, 39, 2715–2725.
(7) Kenny, P. J.; File, S. E.; Neal, M. J. Evidence for a complex influence
of nicotinic acetylcholine receptors on hippocampal serotonin release.
J. Neurochem. 2000, 75, 2409–2414.
(8) Seth, P.; Cheeta, S.; Tucci, S.; File, S. E. Nicotinic-serotonergic
interactions in brain and behaviour. Pharmacol., Biochem. BehaV.
2002, 71, 795–805.
dimcarb (dimethylamine-carbon dioxide adduct). Pharmazie 1993,
48, 591–597.
(29) Negi, S.; Yamanaka, M.; Sugiyama, I.; Komatsu, Y.; Sasho, M.;
Tsuruoka, A.; Kamada, A.; Tsukada, I.; Hiruma, R.; Katsu, K.;
Machida, Y. Studies on orally-active cephalosporins. I. Synthesis and
structure-activity relationships of new 3-substituted carbamoyloxym-
ethyl cephalosporins. J. Antibiot. 1994, 47, 1507–1525.
(30) Combrink, K. D.; Denton, D. A.; Harran, S.; Ma, Z.; Chapo, K.; Yan,
D.; Bonventre, E.; Roche, E. D.; Doyle, T. B.; Robertson, G. T.; Lynch,
A. S. New C25 carbamate rifamycin derivatives are resistant to
inactivation by ADP-ribosyl transferases. Bioorg. Med. Chem. Lett.
2007, 17, 522–526.
(31) Couty, F.; Evano, G.; Vargas-Sanchez, M.; Bouzas, G. Practical
asymmetric preparation of azetidine-2-carboxylic acid. J. Org. Chem.
2005, 70, 9028–9031.
(32) Rutjes, F. P. J. T.; Tjen, K. C. M. F.; Wolf, L. B.; Karstens, W. F. J.;
Schoemaker, H. E.; Hiemstra, H. Selective azetidine and tetrahydro-
pyridine formation via Pd-catalyzed cyclizations of allene-substituted
amines and amino acids. Org. Lett. 1999, 1, 717–720.
(33) Barluenga, J.; Ferna´ndez-Mari, F.; Viado, A. L.; Aguilar, E.; Olano,
B. Diastereospecific synthesis of enantiomerically pure polysubstituted
azetidines from 1,3-amino alcohols with three chiral centers. J. Org.
Chem. 1996, 61, 5659–5662.
(34) de Figueiredo, R. M.; Fro¨hlich, R.; Christmann, M. N,N ′-Carbonyl-
diimidazole-mediated cyclization of amino alcohols to substituted
azetidines and other N-heterocycles. J. Org. Chem. 2006, 71, 4147–
4154.
(9) Ueda, M.; Iida, Y.; Kitamura, Y.; Kawashima, H.; Ogawa, M.; Magata,
Y.; Saji, H. 5-Iodo-A-85380, a specific ligand for R4ꢀ2 nicotinic
acetylcholine receptors, prevents glutamate neurotoxicity in rat cortical
cultured neurons. Brain Res. 2008, 1199, 46–52.
(10) Grady, S. R.; Salminen, O.; Laverty, D. C.; Whiteaker, P.; McIntosh,
J. M.; Collins, A. C.; Marks, M. J. The subtypes of nicotinic
acetylcholine receptors on dopaminergic terminals of mouse striatum.
Biochem. Pharmacol. 2007, 74, 1235–1246.
(11) Janhunen, S.; Ahtee, L. Differential nicotinic regulation of the
nigrostriatal and mesolimbic dopaminergic pathways: implications for
drug development. Neurosci. BiobehaV. ReV. 2007, 31, 287–314.
(12) Dehkordi, O.; Millis, R. M.; Dennis, G. C.; Jazini, E.; Williams, C.;
Hussain, D.; Jayam-Trouth, A. Expression of alpha-7 and alpha-4
nicotinic acetylcholine receptors by GABAergic neurons of rostral
ventral medulla and caudal pons. Brain Res. 2007, 1185, 95–102.
(13) Rollema, H.; Chambers, L. K.; Coe, J. W.; Glowa, J.; Hurst, R. S.;
Lebel, L. A.; Lu, Y.; Mansbach, R. S.; Mather, R. J.; Rovetti, C. C.;
Sands, S. B.; Schaeffer, E.; Schulz, D. W.; Tingley, F. D., III.;
Williams, K. E. Pharmacological profile of the R4ꢀ2 nicotinic
acetylcholine receptor partial agonist varenicline, an effective smoking
cessation aid. Neuropharmacology 2007, 52, 985–994.
(35) Hillier, M. C.; Chen, C.-Y. A one-pot preparation of 1,3-disubstituted
azetidines. J. Org. Chem. 2006, 71, 7885–7887.
(36) Dejaegher, Y.; Kuz’menok, N. M.; Zvonok, A. M.; De Kimpe, N.
The chemistry of azetidin-3-ones, oxetan-3-ones, and thietan-3-ones.
Chem. ReV. 2002, 102, 29–60.
(37) Forbes, J. E.; Saicic, R. N.; Zard, S. Z. New radical reactions of
S-alkoxycarbonyl xanthates. Total synthesis of (()-cinnamolide and
(()-metlhylenolactocin. Tetrahedron 1999, 55, 3791–3802.
(38) Huang, H.; Iwasawa, N.; Mukaiyama, T. A convenient method for
the construction of ꢀ-lactam compounds from ꢀ-amino acids using
2-chloro-1-methylpyridinium iodide as condensing reagent. Chem. Lett.
1984, 1465–1466.
(39) Nilsson, B. M.; Ringdahl, B.; Hacksell, U. ꢀ-Lactam analogs of
oxotremorine: 3- and 4-methyl-substituted 2-azetidinones. J. Med.
Chem. 1990, 33, 580–584.
(40) Ojima, I.; Zhao, M. Z.; Yamato, T.; Nakahashi, K.; Yamashita, M.;
Abe, R. Azetidines and bisazetidines. Their synthesis and use as the
key intermediates to enantiomerically pure diamines, amino-alcohols,
and polyamines. J. Org. Chem. 1991, 56, 5263–5277.
(41) Van Brabandt, W.; Dejaegher, Y.; Van Landeghem, R.; De Kimpe,
N. Reduction of 4-(haloalkyl)azetidin-2-ones with LiAlH4 as a
powerful method for the synthesis of stereodefined aziridines and
azetidines. Org. Lett. 2006, 8, 1101–1104.
(42) Yamashita, M.; Ojima, I. Effective route to azetidines from azetidin-
2-ones using hydroalanes as specific reducing agents. J. Am. Chem.
Soc. 1983, 105, 6339–6342.
(43) Bandini, E.; Favi, G.; Martelli, G.; Panunzio, M.; Piersanti, G. A trans-
stereoselective synthesis of 3-halo-4-alkyl(aryl)-NH-azetidin-2-ones.
Org. Lett. 2000, 2, 1077–1079.
(44) Evans, P. A.; Holmes, A. B.; McGeary, R. P.; Nadin, A.; Russell, K.;
O’Hanlon, P. J.; Pearson, N. D. New methodology for the synthesis
of unsaturated 8-, 9- and 10-membered lactams. J. Chem. Soc., Perkin
Trans. 1 1996, 123–138.
(45) Vaughan, W. R.; Klonowski, R. S.; McElhinney, R. S.; Millward, B. B.
Synthesis of potential anticancer agents.V. Azetidines. J. Org. Chem.
1961, 26, 138.
(14) Fujita, M.; Ichise, M.; Zoghbi, S. S.; Liow, J.-S.; Ghose, S.; Vines,
D. C.; Sangare, J.; Lu, J.-Q.; Cropley, V. L.; Iida, H.; Kim, K. M.;
Cohen, R. M.; Bara-Jimenez, W.; Ravina, B.; Innis, R. B. Widespread
decrease of nicotinic acetylcholine receptors in Parkinson’s disease.
Ann. Neurol. 2006, 59, 174–177.
(15) Gotti, C.; Clementi, F. Neuronal nicotinic receptors: from structure
to pathology. Prog. Neurobiol. 2004, 74, 363–396.
(16) Oddo, S.; LaFerla, F. M. The role of nicotinic acetylcholine receptors
in Alzheimer’s disease. J. Physiol. (Paris) 2006, 99, 172–179.
(17) Paterson, D.; Nordberg, A. Neuronal nicotinic receptors in the human
brain. Prog. Neurobiol. 2000, 61, 75–111.
(18) Kulak, J. M.; Fan, H.; Schneider, J. S. ꢀ2* and ꢀ4* nicotinic
acetylcholine receptor expression changes with progressive parkin-
sonism in non-human primates. Neurobiol. Dis. 2007, 27, 312–319.
(19) Marini, C.; Guerrini, R. The role of the nicotinic acetylcholine receptors
in sleep-related epilepsy. Biochem. Pharmacol. 2007, 74, 1308–1314.
(20) Gotti, C.; Riganti, L.; Vailati, S.; Clementi, F. Brain neuronal nicotinic
receptors as new targets for drug discovery. Curr. Pharm. Des. 2006,
12, 407–428.
(21) Picciotto, M. R.; Caldarone, B. J.; Brunzell, D. H.; Zachariou, V.;
Stevens, T. R.; King, S. L. Neuronal nicotinic acetylcholine receptor
subunit knockout mice: physiological and behavioral phenotypes and
possible clinical implications. Pharm. Ther. 2001, 92, 89–108.
(22) Hilf, R. J. C.; Dutzler, R. X-ray structure of a prokaryotic pentameric
ligand-gated ion channel. Nature 2008, 452, 375.
(23) Brejc, K.; van Dijk, W. J.; Klaassen, R. V.; Schuurmans, M.; van der
Oost, J.; Smit, A. B.; Sixma, T. K. Crystal structure of an ACh-binding
protein reveals the ligand-binding domain of nicotinic receptors. Nature
2001, 411, 269–276.
(24) Dellisanti, C. D.; Yao, Y.; Stroud, J. C.; Wang, Z.-Z.; Chen, L. Crystal
structure of the extracellular domain of nAChR R1 bound to R-bun-
garotoxin at 1.94 Å resolution. Nat. Neurosci. 2007, 10 (8), 953–962.
(25) Jensen, A. A.; Mikkelsen, I.; Frølund, B.; Frydenvang, K.; Brehm,
L.; Jaroszewski, J. W.; Bra¨uner-Osborne, H.; Falch, E.; Krogsgaard-
Larsen, P. Carbamoylcholine homologs: synthesis and pharmacology
at nicotinic acetylcholine receptors. Eur. J. Pharmacol. 2004, 497,
125–137.
(26) Jensen, A. A.; Mikkelsen, I.; Frølund, B.; Bra¨uner-Osborne, H.; Falch,
E.; Krogsgaard-Larsen, P. Carbamoylcholine homologs: novel and
potent agonists at neuronal nicotinic acetylcholine receptors. Mol.
Pharmacol. 2003, 64, 865–875.
(46) Thompson, H. W.; Swistok, J. Enamines of 3,3-dimethylazetidine. J.
Org. Chem. 1981, 46, 4907–4911.
(47) Boger, D. L.; Patel, M. Activation and coupling of pyrrole-1-carboxylic
acid in the formation of pyrrole N-carbonyl compounds: pyrrole-1-
carboxylic acid anhydride. J. Org. Chem. 1987, 52, 2319–2323.
(48) Kinas, R.; Pankiewicz, K.; Stec, W. J.; Farmer, P. B.; Foster, A. B.;
Jarman, M. Synthesis and absolute configuration of optically active
forms of 2-[bis(2-chloroethyl)amino]-4-methyltetrahydro-2H-1,3,2-
oxazaphosphorine 2-oxide(4-methylcyclophosphamide). J. Org. Chem.
1977, 42, 1650–1652.
(49) Yamagishi, T.; Fujii, K.; Shibuya, S.; Yokomatsu, T. Asymmetric
synthesis of phosphonic acid analogues for acylcarnitine. Tetrahedron
2006, 62, 54–65.
(50) Paquette, L. A.; Mitzel, T. M.; Isaac, M. B.; Crasto, C. R.; Schomer,
W. W. Diastereoselection during 1,2-addition of the allylindium reagent
to R-thia and R-amino aldehydes in aqueous and organic solvents. J.
Org. Chem. 1997, 62, 8960.
(27) Adamson, D. W. Aminoalkyl tertiary carbinols and derived products.
Part II. 3-Amino-1-1-di-2′-thienyl-alkan-1-ols and -alken-1-enes.
J. Chem. Soc. 1950, 885–890.
(51) Jeffery, G. H.; Vogel, A. I. Physical properties and chemical
constitution. 18. 3-Membered and 4-membered carbon rings. J. Chem.
Soc. 1948, 1804–1809.
(28) Hess, U.; Dunkel, S.; Mueller, B. Synthesis of ꢀ-amino acid derivatives
via reductive amination of unsaturated carboxylic acid derivatives in