- Preparation of enantiopure 2-acylazetidines and their reactions with chloroformates
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Enantiopure 1-phenylethylazetidine-2-carboxylates and 2-acylazetidines were prepared and reacted with chloroformates to yield α-chloro-γ-amino butyric acid esters and ketones from ring opening reaction of azetidinium ion intermediate in a completely regio- and stereoselective manner.
- Ma, Sang-ho,Yoon, Doo Ha,Ha, Hyun-Joon,Lee, Won Koo
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p. 269 - 271
(2007/10/03)
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- Practical asymmetric preparation of azetidine-2-carboxylic acid
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Facile and straightforward syntheses of both enantiomers of azetidine-2-carboxylic acid are described. The syntheses depart from inexpensive chemicals and allow for the production, in five to six steps, of practical quantities of each enantiomer. Synthetic highlights include the construction of the azetidine ring using an intramolecular alkylation and the use of optically active α-methylbenzylamine as chiral auxiliary.
- Couty, Francois,Evano, Gwilherm,Vargas-Sanchez, Monica,Bouzas, Gloria
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p. 9028 - 9031
(2007/10/03)
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- 3-Pyridyl enantiomers and their use as analgesics
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The present invention relates to a method of controlling pain in mammals, including humans, comprising administering to a mammal or patient in need of treatment thereof selected compounds of formula I: STR1 or a pharmaceutically acceptable salt thereof. The invention further relates to selected (R) and (S) compounds of formula I above which are useful as analgesics as well as neuronal cell death preventors and anti-inflammatories.
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- Identification and initial structure-activity relationships of (R)-5- (2-azetidinylmethoxy)-2-chloropyridine (ABT-594), a potent, orally active, non-opiate analgesic agent acting via neuronal nicotinic acetylcholine receptors
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New members of a previously reported series of 3-pyridyl ether compounds are disclosed as novel, potent analgesic agents acting through neuronal nicotinic acetylcholine receptors. Both (R)-2-chloro-5-(2- azetidinylmethoxy)pyridine (ABT-594, 5) and its S-enantiomer (4) show potent analgesic activity in the mouse hot-plate assay following either intraperitoneal (ip) or oral (po) administration, as well as activity in the mouse abdominal constriction (writhing) assay, a model of persistent pain. Compared to the S-enantiomer and to the prototypical potent nicotinic analgesic agent (±)-epibatidine, 5 shows diminished activity in models of peripheral side effects. Structure-activity studies of analogues related to 4 and 5 suggest that the N-unsubstituted azetidine moiety and the 2-chloro substituent on the pyridine ring are important contributors to potent analgesic activity.
- Holladay, Mark W.,Wasicak, James T.,Lin, Nan-Horng,He, Yun,Ryther, Keith,Bannon, Anthony W.,Buckley, Michael J.,Kim, David J. B.,Decker, Michael W.,Anderson, David J.,Campbell, Jeffrey E.,Kuntzweiler, Theresa A.,Donnelly-Roberts, Diana L.,Piattoni-Kaplan, Marietta,Briggs, Clark A.,Williams, Michael,Arneric, Stephen P.
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p. 407 - 412
(2007/10/03)
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