124815-67-4

Upstream product

• 5669-19-2 2-Benzyl-2-propenoic acid 
• 507-09-5 tiolacetic acid 
• 174858-24-3 (S)-2-benzyl-3-chloropropionic acid 
• 10387-40-3 potassium thioacetate 
• 2612-30-8 2-benzyl-1,3-propanediol 
• 174858-26-5 (Z)-2-benzylidene-3-chloropropionic acid 
• 201999-33-9 (R)-2-benzyl-3-methanesulfonyloxypropionic acid 
• 7722-64-7 potassium permanganate 
• 91702-98-6 3-acetylthio-2-benzylpropanoic acid 
• 158293-54-0 2-acetylthiomethyl-3-phenylpropanoic acid methyl ester 
• 90788-17-3 DL-methyl 2-<(dimethylamino)methyl>-3-phenylpropionate 
• 100-39-0 benzyl bromide 
• 174858-25-4 methyl (2Z)-2-(chloromethyl)-3-phenylprop-2-enoate 
• 100-52-7 benzaldehyde 

Downstream Products

• 150133-56-5 Thioacetic acid S-((S)-2-chlorocarbonyl-3-phenyl-propyl) ester 
• 124820-05-9 Thioacetic acid S-((R)-2-chlorocarbonyl-3-phenyl-propyl) ester 
• 1043608-76-9 Thioacetic acid S-((S)-2-{2-[pentanoyl-(2'-sulfamoylbiphenyl-4-ylmethyl)amino]ethylcarbamoyl}-3-phenylpropyl) ester 
• 116111-86-5 Sodium; 2-((S)-2-mercaptomethyl-3-phenyl-propionylamino)-ethanesulfonate 
• 116111-85-4 Sodium; 2-((R)-2-mercaptomethyl-3-phenyl-propionylamino)-ethanesulfonate 
• 116112-13-1 Sodium; 2-((S)-2-acetylsulfanylmethyl-3-phenyl-propionylamino)-ethanesulfonate 
• 116112-14-2 Sodium; 2-((R)-2-acetylsulfanylmethyl-3-phenyl-propionylamino)-ethanesulfonate 
• 182479-25-0 (S)-3-(1H-Indol-3-yl)-2-((S)-2-mercaptomethyl-3-phenyl-propionylamino)-propionic acid methyl ester 
• 81110-73-8 N-(S-2-acetylthiomethyl-1-oxo-3-phenylpropyl)-glycine benzyl ester 

Relevant academic research and scientific papers

New orally active dual enkephalinase inhibitors (DENKIs) for central and peripheral pain treatment

Protecting enkephalins, endogenous opioid peptides released in response to nociceptive stimuli, is an innovative approach for acute and neuropathic pain alleviation. This is achieved by inhibition of their enzymatic degradation by two membrane-bound Zn-metallopeptidases, neprilysin (NEP, EC 3.4.24.11) and aminopeptidase N (APN, EC 3.4.11.2). Selective and efficient inhibitors of both enzymes, designated enkephalinases, have been designed that markedly increase extracellular concentrations and half-lives of enkephalins, inducing potent antinociceptive effects. Several chemical families of Dual ENKephalinase Inhibitors (DENKIs) have previously been developed but devoid of oral activity. We report here the design and synthesis of new pro-drugs, derived from co-drugs combining a NEP and an APN inhibitor through a disulfide bond with side chains improving oral bioavailability. Their pharmacological properties were assessed in various animal models of pain targeting central and/or peripheral opioid systems. Considering its efficacy in acute and neuropathic pain, one of these new DENKIs, 19-IIIa, was selected for clinical development.

Dual-acting antihypertensive agents

The invention is directed to compounds of formula I: wherein Ar, r, R3, X, and R5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula I have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and a process and intermediates for preparing such compounds.

PROCESS FOR PRODUCING 2-ARALKYLPROPIONIC ACID DERIVATIVE

A process for easily and industrially advantageously producing a high-purity 2-aralkyl-3-acetylthiopropionic acid and a high-purity 2-aralkylpropionic acid having a leaving group in the 3-position from easily available compounds. A 2-aralkyl-1-propanol ha

New asymmetric synthesis of dexecadotril and ecadotril starting from a single precursor

We describe herein a method providing access to both enantiomers of 3-acetylthio-2-benzylpropionic acid via enzymatic desymmetrization of 2-benzyl-1,3-propanediol. These compounds are respectively the starting materials for the synthesis of ecadotril, and dexecadotril, which are powerful inhibitors of NEP (EC 3.4.24.11) and have been developed as therapeutic agents.

The synthesis of (S)-3-acetylthio-2-benzylpropionic acid from (Z)-2-chloromethyl-3-phenylprop-2-enoic acid by asymmetric hydrogenation: A chiral building block of an enkephalinase inhibitor

(S)-2-Benzyl-3-chloropropionic acid (7) was synthesized from (Z)-2-(chloromethyl)-3-phenylprop-2-enoic acid (5) by asymmetric hydrogenation with a ruthenium 2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl complex in the presence of triethylamine. Acetylthio

Thiol inhibitors of endothelin-converting enzyme

Synthesis and structure activity relationships of a series of thiol inhibitors of the endothelin-converting enzyme (ECE) are presented. Optimisation of the stereochemistry as well as of the P'1 and P'2 residues led to inhibitors with similar potency to that of phosphoramidon.

A novel class of enkephalinase inhibitors containing a C-terminal sulfo group

A new series of sulfonic acids were synthesized and tested for their enkephalinase inhibitory activity. Among them, the most potent was N-(2- benzyl-3-mercaptopropionyl)metanilic acid 10i with an IC50 value of 0.27 nM. Several other analogues (10a,b,j,n,o,gg,hh) showed the inhibitory activity comparable to or greater than thiorphan (IC50 = 2.6 nM), a C- terminal carboxyl-containing inhibitor of enkephalinase. Thus compounds containing a C-terminal sulfo group, instead of the C-terminal carboxyl group, were found to show a remarkably high level of inhibition of enkephalinase. The analgesic activity of 10b, (S)-10b, and (R)-10b was also evaluated by the phenylbenzoquinone writhing test.