820253-34-7Relevant articles and documents
Potent α-amino-β-lactam carbamic acid ester as NAAA inhibitors. Synthesis and structure-activity relationship (SAR) studies
Nuzzi, Andrea,Fiasella, Annalisa,Ortega, Jose Antonio,Pagliuca, Chiara,Ponzano, Stefano,Pizzirani, Daniela,Bertozzi, Sine Mandrup,Ottonello, Giuliana,Tarozzo, Glauco,Reggiani, Angelo,Bandiera, Tiziano,Bertozzi, Fabio,Piomelli, Daniele
supporting information, p. 138 - 159 (2016/02/18)
4-Cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]carbamate (3b) is a potent, selective and systemically active inhibitor of intracellular NAAA activity, which produces profound anti-inflammatory effects in animal models. In the present work, we describe structure-activity relationship (SAR) studies on 3-aminoazetidin-2-one derivatives, which have led to the identification of 3b, and expand these studies to elucidate the principal structural and stereochemical features needed to achieve effective NAAA inhibition. Investigations on the influence of the substitution at the β-position of the 2-oxo-3-azetidinyl ring as well as on the effect of size and shape of the carbamic acid ester side chain led to the discovery of 3ak, a novel inhibitor of human NAAA that shows an improved physicochemical and drug-like profile relative to 3b. This favourable profile, along with the structural diversity of the carbamic acid chain of 3b, identify this compound as a promising new tool to investigate the potential of NAAA inhibitors as therapeutic agents for the treatment of pain and inflammation.
Stereoselective, temperature-dependent [2+2] cycloaddition of N,N-dialkylhydrazones to N-benzyl-N-(benzyloxycarbonyl)aminoketene
Marques-Lopez, Eugenia,Martin-Zamora, Eloisa,Diez, Elena,Fernandez, Rosario,Lassaletta, Jose M.
experimental part, p. 2960 - 2972 (2009/04/06)
The Staudinger-like [2+2] cycloaddition of aliphatic hydrazones derived from (2R,5R)-1-amino-2,5-dimethylpyrrolidine to N-benzyl-N-(benzyloxycarbonyl) aminoketene takes place to afford the corresponding β-lactams in good yields when iPr2EtN is
Asymmetric synthesis of trans-3-amino-4-alkylazetidin-2-ones from chiral N,N-dialkylhydrazones
Diez, Elena,Fernandez, Rosario,Marques-Lopez, Eugenia,Martin-Zamora, Eloisa,Lassaletta, Jose M.
, p. 2749 - 2752 (2007/10/03)
Enantiopure N,N-dialkylhydrazones 3 smoothly react with N-benzyloxycarbonyl-N-benzyl glycine as an aminoketene precursor to afford trans-3-amino-4-alkylazetidin-2-ones 4 as single diasteromers. As an exception, hydrazone 3f (R = OBn) affords cis-(3R,4R)-4
β-lactams from ester enolates and silylimines: An enantiospecific synthesis of monocyclic β-lactams
Andreoli,Billi,Cainelli,Panunzio,Bandini,Martelli,Spunta
, p. 9061 - 9070 (2007/10/02)
Optically active 3,4-disubstituted azetidin-2-ones have been prepared by annelation of chiral silylimines derived from (S) or (R)-lactaldehyde with the ester enolate of the ethyl 2,2,5,5-tetramethyl-1,2,5-azadisilolidin-1-acetate (STABASE). Oxidation of the hydroxyethyl side chain on the C-4 position of the β-lactam ring, followed by Baeyer-Villiger oxidation led to the optically active (3S, 4S) 3-amino-4-acetoxy-β-lactam. The absolute configuration of this compound was determined by elaboration of this substrate to a key intermediate in the synthesis of the antibiotic 'Aztreonam'. Nucleophilic displacement of the acetoxy group led to optically active 3-amino-4-alkyl(aryl)-azetidin-2-ones.
The Synthesis of Substituted thio>acetic Acids
Woulfe, Steven R.,Miller, Marvin J.
, p. 3133 - 3139 (2007/10/02)
The synthesis of substituted thio>acetic acids (6, thiamazins) is described.Various substituted 3(S)-(acylamino)-2-azetidinones were sulfenylated with tert-butyl (phtalimidothio)acetate.Deprotection of the tert-butyl ester with trifluoroacetic acid provided the title compounds.In sharp contrast to their oxygen analogues (oxamazins), the thiamazins were devoid of biological activity.
