124815-67-4Relevant articles and documents
New orally active dual enkephalinase inhibitors (DENKIs) for central and peripheral pain treatment
Poras, Hervé,Bonnard, Elisabeth,Dangé, Emilie,Fournié-Zaluski, Marie-Claude,Roques, Bernard P.
supporting information, p. 5748 - 5763 (2014/08/05)
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.
PROCESS FOR PRODUCING 2-ARALKYLPROPIONIC ACID DERIVATIVE
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Page 12, (2008/06/13)
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
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
Yuasa, Yoko,Yuasa, Yoshifumi,Tsuruta, Haruki
, p. 511 - 514 (2007/10/03)
(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