26555-40-8Relevant articles and documents
A ring opening reaction of benzisothiazolones. A new route to unsymmetrical disulfides
Sanchez, Joseph P.
, p. 1463 - 1467 (1997)
A series of unsymmetrical disulfides has been prepared by employing a reaction involving a ring opening, nucleophilic attack of a thiol on a 1,2- benzisothiazol-3-one. The benzisothiazolones were in turn prepared by an intramolecular ring closure of an am
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.
, 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.
Labeling nucleic acids
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, (2008/06/13)
Reagents and methods for multi-step labeling of nucleic acids allow the addition of relatively insoluble or unstable labels to nucleic acid in the final step. Nucleic acids can be stored as a stable intermediate capable of reacting with a label conjugated to a thiol-reactive group.
