17107-25-4

Upstream product

• 89848-92-0 (2S,3R)-3-Phenyl-oxirane-2-carbonyl azide 
• 70-11-1 α-bromoacetophenone 
• 88419-13-0 2,4-dioxo-3-thiazolidinylmethyl phenyl ketone azine 
• 61416-36-2 imidazole-1-carboxylic acid 2-oxo-2-phenyl-ethylamide 
• 72674-72-7 N-benzoyloxy-3-oxo-3-phenyl-propionamide 
• 88419-01-6 3-(2-oxo-2-phenylethyl)thiazolidine-2,4-dione 

Downstream Products

• 67322-89-8 2-oxo-5-phenyl-oxazole-3-carboxylic acid ethyl ester 
• 59167-75-8 2-oxo-N,5-diphenyl-oxazole-3-carboxamide 
• 59167-73-6 2-oxo-5-phenyl-oxazole-3-carboxylic acid methylamide 
• 67322-87-6 3-chloroacetyl-5-phenyl-3H-oxazol-2-one 
• 59167-74-7 2-oxo-5-phenyl-oxazole-3-carboxylic acid ethylamide 
• 67322-88-7 2-oxo-5-phenyl-oxazole-3-carboxylic acid dimethylamide 
• 67322-95-6 4-(2-dimethylamino-oxazol-5-yl)-benzenesulfonic acid 
• 3969-09-3 2-methyl-5-phenyl-1,3-oxazole 
• 64640-13-7 2-Chloromethyl-5-phenyloxazole 
• 65647-69-0 3-acetyl-5-phenyl-3H-oxazol-2-one 

Relevant academic research and scientific papers

Design, Synthesis, and Biological Evaluation of a Series of Oxazolone Carboxamides as a Novel Class of Acid Ceramidase Inhibitors

Acid ceramidase (AC) is a cysteine hydrolase that plays a crucial role in the metabolism of lysosomal ceramides, important members of the sphingolipid family, a diversified class of bioactive molecules that mediate many biological processes ranging from cell structural integrity, signaling, and cell proliferation to cell death. In the effort to expand the structural diversity of the existing collection of AC inhibitors, a novel class of substituted oxazol-2-one-3-carboxamides were designed and synthesized. Herein, we present the chemical optimization of our initial hits, 2-oxo-4-phenyl-N-(4-phenylbutyl)oxazole-3-carboxamide 8a and 2-oxo-5-phenyl-N-(4-phenylbutyl)oxazole-3-carboxamide 12a, which resulted in the identification of 5-[4-fluoro-2-(1-methyl-4-piperidyl)phenyl]-2-oxo-N-pentyl-oxazole-3-carboxamide 32b as a potent AC inhibitor with optimal physicochemical and metabolic properties, showing target engagement in human neuroblastoma SH-SY5Y cells and a desirable pharmacokinetic profile in mice, following intravenous and oral administration. 32b enriches the arsenal of promising lead compounds that may therefore act as useful pharmacological tools for investigating the potential therapeutic effects of AC inhibition in relevant sphingolipid-mediated disorders.

Synthesis of α,β-Epoxyacyl Azides and Their Rearrangement to Epoxy Isocyanates and 3- and 4-Oxazolin-2-ones

The conversion of α,β-epoxy carboxylates 6 into α,β-epoxyacyl azides 4 proceeds either via reaction of the mixed anhydrides 7 with sodium azide or via reaction of epoxyacyl chlorides 8 with hydrazoic acid-pyridine.The latter method is preferred.The azides 4 undergo a smooth thermal Curtius rearrangement to give 4-oxazolin-2-ones 10 for the substrates 4a-h having a hydrogen atom at C(β).Monitoring this reaction by means of IR shows that the epoxy isocyanates 5 are intermediates.Intramolecular ring expansion of 5 then leads to 3-oxazolin-2-ones 9 that tautomerizeto the 4-isomers 10a-h.Epoxyacyl azides 4i,n-q, having no hydrogen atom at C(β), producing 3-oxazolin-2-ones 9i,n-q by a proton shift is not possible.The products 9i and 9q rapidly add water at the imine bond to give oxazolidin-2-ones 11.Epoxy isocyanate 5k is reasonable stable in solution; reaction with methanol affords urethane 12.

RECYCLIZATION REACTIONS. RECYCLIZATIONS OF 3-ACYLMETHYL-2,4-THIAZOLIDINEDIONES BY THE ACTION OF NUCLEOPHILES

Four directions were established and investigated in the recyclization of 3-acylmethyl-2,4-thiazolidinediones with the participation of the side chain at the cyclic nitrogen atom and the formation of substituted 2-imidazolones or 2-oxazolones (under the influence of ammonia or hydroxides respectively), 2,5-diarylpyrazines (under the influence of methylamine), 6-monosubstituted or 2,6-disubstituted 4,5-dihydro-1,2,4-triazin-3-ones, and 5-substituted 1-amino-2-imidazolones (under the influence of hydrazine and phenylhydrazine).The directions of recyclization with hydrazines are determined by the stereochemical configuration of the intermediate hydrazones; the E-hydrazones of 3-acylmethyl-2,4-thiazolidenediones are converted into 4,5-dihydro-1,2,4-triazin-3-ones, while the Z izomers are converted into 1-amino-2-imidazolones.

Photolysis of 3 hydroxyisoxazoles

Photolysis of 3 hydroxy 5 phenylisoxazole in methanol with a low pressure mercury lamp afforded 5 phenyl 4 oxazolin 2 one, together with small amounts of benzoic acid and benzoylacetamide. Similarly, 3 hydroxy 5 methylisoxazole in distilled water afforded 5 methyl 4 oxazolin 2 one as the major product. Both isoxazoles were stable in sunlight for up to 20 days.