- Primary amino acid derivatives: Compounds with anticonvulsant and neuropathic pain protection activities
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Pharmacological management remains the primary method to treat epilepsy and neuropathic pain. We have advanced a novel class of anticonvulsants termed functionalized amino acids (FAAs). In this study, we examine FAA derivatives from which the terminal acetyl moiety was removed and termed these compounds primary amino acid derivatives (PAADs). Twenty-seven PAADs were prepared; the central C(2) R-substituent was varied, including C(2) stereochemistry, and the compounds were tested in rodent models of seizures and neuropathic pain. C(2)-Hydrocarbon N-benzylamide PAADs were potent anticonvulsants and excellent anticonvulsant activity (mice, ip; rat, po) was observed for C(2) R-substituted PAADs in which the R group was ethyl, isopropyl, or tert-butyl, and the C(2) stereochemistry conformed to the d-amino acid configuration ((R)-stereoisomer). These values surpassed the activities of several clinical antiepileptic drugs. The C(2) (R)-ethyl and C(2) (R)-isopropyl PAADs also displayed excellent activities in the mouse (ip) formalin neuropathic pain model. Significantly, unlike the FAA structure-activity relationship, PAAD anticonvulsant activity increased upon substitution of a methylene unit for a heteroatom in the R-substituent that was one atom removed from the C(2) site, suggesting that these PAADs function by a different pathway than FAAs.
- King, Amber M.,Salomé, Christophe,Dinsmore, Jason,Salomé-Grosjean, Elise,De Ryck, Marc,Kaminski, Rafal,Valade, Anne,Kohn, Harold
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supporting information; experimental part
p. 4815 - 4830
(2011/10/01)
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- ARYLGLYCINE DERIVATIVES FOR USE AS GLYCINE TRANSPORT INHIBITORS
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The present invention relates to compounds of Formula (I) and salts solvates and hydrates thereof. The invention further relates to pharmaceutical compositions containing said compounds and methods of treating neurological and neuropsychistric disorders using said compounds.
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- The scope of the direct proline-catalyzed asymmetric addition of ketones to imines
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A full account of catalytic direct asymmetric Mannich-type reactions is presented describing the scope of amino acid-catalyzed additions of unmodified ketones to a large variety of imines. These reactions are performed under very mild, operationally simpl
- Notz, Wolfgang,Watanabe, Shin-Ichi,Chowdari, Naidu S.,Zhong, Guofu,Betancort, Juan M.,Tanaka, Fujie,Barbas III, Carlos F.
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p. 1131 - 1140
(2007/10/03)
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- Chiral electrophilic 'glycinal' equivalents. New synthons for optically active α-amino acids and 4-substituted 2-oxazolidinones
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The thermal reaction of 3-[(1S)-2-alkoxy-1-apocamphanecarbonyl]-2-oxazolones (21a-c) with dialkyl azodicarboxylates (9) results in exclusive formation of [4 + 2] type cycloadducts (22 and 23) with moderate levels of diastereofacial selection (up to 72% d.e.). The diastereomers thus obtained were readily purified and subsequent treatment with acidic methanol followed by removal of the auxiliary with LiBH4/MeOH (1:2) gave optically pure 4-methoxy-5-hydrazino-2-oxazolidinones (26 and 27), which serve as α-aminoaldehyde templates useful for the synthesis of a wide variety of optically active α-amino acids as well as 4-alkyl and 4-aryl-2-oxazolidinones.
- Matsunaga, Hirofumi,Ishizuka, Tadao,Kunieda, Takehisa
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p. 1275 - 1294
(2007/10/03)
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