80582-05-4

Upstream product

• 5618-95-1 (2R,3S)-2-{[(benzyloxy)carbonyl]amino}-3-hydroxybutanoic acid 
• 139236-87-6 (3R,4S)-3-(benzyloxycarbonylamino)-4-(1'-oxo-ethyl)-azetidin-2-one 
• 139111-02-7 (1'R,3R,4S)-3-(benzyloxycarbonylamino)-4-(1'-hydroxyethyl)-azetidin-2-one 
• 917-54-4 methyllithium 
• 139236-88-7 (3R,4R)-3-(benzyloxycarbonylamino)-4-acetoxy-azetidin-2-one 
• 112026-39-8 ethyl 3-(p-anisidino)-2-(benzyloxycarbonylamino)butanoate 
• 112026-38-7 ethyl (p-anisidino)-2-(benzoyloxycarbonylamino)but-2-enoate 
• 112026-37-6 ethyl 2-(benzyloxycarbonylamino)acetoacetate 
• 93591-09-4 STABASE 
• 501-53-1 benzyl chloroformate 
• 112026-40-1 cis-3-benzyloxycarbonylamino-N-(4-methoxyphenyl)-4-methylazetidin-2-one 
• 139236-86-5 (1'R,3R,4S)-3-(benzyloxycarbonylamino)-4-(1'-tert-butyldimethylsilyloxy-ethyl)-azetidin-2-one 

Downstream Products

• 745074-59-3 trans-(3R,4R)-3-amino-methylazetidin-2-one 
• 80082-62-8 (2R,3S)-3-Benzyloxycarbonylamino-2-methyl-4-oxo-azetidine-1-sulfonatetetrabutyl-ammonium; 

Relevant academic research and scientific papers

Potent α-amino-β-lactam carbamic acid ester as NAAA inhibitors. Synthesis and structure-activity relationship (SAR) studies

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.

CARBAMATE DERIVATIVES OF LACTAM BASED N-ACYLETHANOLAMINE ACID AMIDASE (NAAA) INHIBITORS

Described herein are compounds and pharmaceutical compositions which inhibit N-acylethanolamine acid amidase (NAAA). Described herein are methods for synthesizing the compounds set forth herein and methods for formulating these compounds as pharmaceutical compositions which include these compounds. Also described herein are methods of inhibiting NAAA in order to sustain the levels of palmitoylethanolamide (PEA) and other N-acylethanolamines (NAE) that are substrates for NAAA, in conditions characterized by reduced concentrations of NAE. Also, described here are methods of treating and ameliorating pain, inflammation, inflammatory diseases, and other disorders in which modulation of fatty acid ethanolamides is clinically or therapeutically relevant or in which decreased levels of NAE are associated with the disorder.

β-lactams from ester enolates and silylimines: An enantiospecific synthesis of monocyclic β-lactams

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.

Stereoselective synthesis of cis-4-(substituted) monobactams from ethyl acetoacetate

The stereoselective synthesis of cis-3-amino-4-methyl-2-oxoazetidine-1-sulphonic acid (25) from ethyl acetoacetate is described. Nitrosation of this compound and reduction of the resulting oxime gave the corresponding amine, which after treatment with different acyl halides, yielded the acylamino derivatives (6)-(8). Condensation with p-anisidine gave the enamines (12)-(14), which were then reduced to the β-amino acid esters (15)-(17). Stereoselective cyclization with Grignard reagents as base, and appropriate deprotection and sulphonation of the resulting β-lactams (18)-(20), led to the title compounds.