65935-40-2

Upstream product

• 75-44-5 phosgene 
• 122-97-4 3-Phenyl-1-propanol 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 121-44-8 triethylamine 
• 503-38-8 trichloromethyl chloroformate 

Downstream Products

• 38593-37-2 4-(3-Phenyl-propoxycarbonylamino)-benzoic acid 
• 37626-89-4 4-(3-Phenyl-propoxycarbonyloxy)-benzoic acid 
• 736143-92-3 ((S)-1-Hydroxymethyl-pentyl)-carbamic acid 3-phenyl-propyl ester 
• 122-97-4 3-Phenyl-1-propanol 
• 1439366-52-5 3-phenylpropyl N-[(2S,3R)-2-methyl-4-oxooxetan-3 - yl]carbamate 
• 1439367-14-2 (2R,3S)-3-hydroxy-2-{[(3-phenylpropoxy)carbonyl]amino}butanoic acid 
• 525584-13-8 1-(3'-phenylpropyloxycarbonyl)-(3S)-(t-butoxycarbonyl)aminoazetidin-2-one 

Relevant academic research and scientific papers

Microelectrode Arrays, Dihydroxylation, and the Development of an Orthogonal Safety-Catch Linker

Construction of larger molecular libraries on an addressable microelectrode array requires a method for recovering and characterizing molecules from the surface of any electrode in the array. This method must be orthogonal to the synthetic strategies needed to build the array. We report here a method for achieving this goal that employs the site-selective dihydroxylation reaction of a simple olefin.

Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)

The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.

Synthesis and structure-activity relationship (SAR) of 2-methyl-4-oxo-3- oxetanylcarbamic acid esters, a class of potent N-acylethanolamine acid amidase (NAAA) inhibitors

N-Acylethanolamine acid amidase (NAAA) is a lysosomal cysteine hydrolase involved in the degradation of saturated and monounsaturated fatty acid ethanolamides (FAEs), a family of endogenous lipid agonists of peroxisome proliferator-activated receptor-α, which include oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). The β-lactone derivatives (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide (2) and (S)-N-(2-oxo-3-oxetanyl)- biphenyl-4-carboxamide (3) inhibit NAAA, prevent FAE hydrolysis in activated inflammatory cells, and reduce tissue reactions to pro-inflammatory stimuli. Recently, our group disclosed ARN077 (4), a potent NAAA inhibitor that is active in vivo by topical administration in rodent models of hyperalgesia and allodynia. In the present study, we investigated the structure-activity relationship (SAR) of threonine-derived β-lactone analogues of compound 4. The main results of this work were an enhancement of the inhibitory potency of β-lactone carbamate derivatives for NAAA and the identification of (4-phenylphenyl)-methyl-N-[(2S,3R)-2-methyl-4-oxo-oxetan-3-yl]carbamate (14q) as the first single-digit nanomolar inhibitor of intracellular NAAA activity (IC50 = 7 nM on both rat NAAA and human NAAA).

DISUBSTITUTED BETA-LACTONES AS INHIBITORS OF N-ACYLETHANOLAMINE ACID AMIDASE (NAAA)

The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.

Chlorination of aliphatic primary alcohols via triphosgene-triethylamine activation

Activation of primary aliphatic alcohols with triphosgene and triethylamine mixtures afforded either alkyl chloride or diethylcarbamate products, and the switch in selectivity appeared to be driven by sterics. The reaction conditions to achieve this highly useful transformation were unexceptionally mild and readily tolerated by a wide range of sensitive functionalities.

Exploration of the P2-P3 SAR of aldehyde cathepsin K inhibitors

The synthesis and biological activity of a series of aldehyde inhibitors of cathepsin K are reported. Exploration of the properties of the S2 and S3 subsites with a series of carbamate derivatized norleucine aldehydes substituted at the P2 and P3 positions afforded analogs with cathepsin K IC50s between 600nM and 130pM.

Dipeptidyl aspartyl fluoromethylketones as potent caspase inhibitors: SAR of the N-protecting group

The synthesis and biological evaluation of a group of N-protected Val-Asp-fmk as caspase inhibitors is reported. This article describes the synthesis and biological evaluation of a group of N-protected Val-Asp-fmk as caspase inhibitors. The protecting group was found to contribute to caspase-3 inhibiting activity, and compounds with a large group such as Cbz are more active than compounds with a small group such as Ac. Compounds with more hydrophobic protecting groups were found to be more active in cell apoptosis protection assays, probably due to increased cell permeability. MX1122, 2,4-di-Cl-Cbz-Val-Asp-fmk, is identified as a potent broad-spectrum caspase inhibitor and is selective for caspases versus other proteases, with good activity in the cell apoptosis protection assays as well as good efficacy in the mouse liver apoptosis model.

Beta lactam compounds and their use as inhibitors of tryptase

Compounds of the formulas: are disclosed. These compounds inhibit tryptase as well as other enzyme systems or are selective tryptase inhibitors and are useful as antiinflammatory agents particularly in the treatment of chronic asthma.

Synthesis, hydrolysis, biochemical and theoretical evaluation of 1,4-bis(alkoxycarbonyl)azetidin-2-ones as potential elastase inhibitors

A series of 1,4-bis(alkoxycarbonyl)azetidin-2-ones, designed as potential suicide-inhibitors of serine proteases, has been synthesized and evaluated against porcine pancreatic elastase (PPE). The most active compound (Ki～10 μM; reversible inhibitor) was equipped with phenethyloxycarbonyl and benzyloxycarbonyl side-chains at positions N1 and C4, respectively, with the (S)-configuration. 1H NMR spectroscopic analysis of the reaction mixtures showed that the ester function is preferentially hydrolyzed, in both chemical and enzyme-catalyzed reactions, with regard to the azetidinone and urethane functions. Considering the three potentially sensitive carbonyl functions and the two stereoisomers, ab initio calculations were performed to determine the energetic barriers required to reach the transition state structures of hydrolysis in a model of the enzyme pocket.

A facile synthesis of azidoformate via chloroformate

This work synthesized chloroformates by slowly adding alcohols into a suspension of trichloromethyl chloroformate, instead of phosgene, along with activated charcoal in tetrahydrofuran. This chloroformylation yielded chloroformates in near quantitative yield. The subsequent reaction between chloroformates and sodium azide in dry acetone produced azidoformates in a high yield.