Synthesis and Characterization of the Selective, Reversible PKC Inhibitor (9 S )-9-(Dimethylamino)methyl-6,7,10,11-tetrahydro-9 H ,18 H -5,21:12,17-dimethenodibenzo e,k pyrrolo3,4- h1,4,13oxadiazacyclohexadecine-18,20(19 H)-dione, Ruboxistaurin (LY333531).

08:00 EDT 29th August 2018 | BioPortfolio

Summary of "Synthesis and Characterization of the Selective, Reversible PKC Inhibitor (9 S )-9-(Dimethylamino)methyl-6,7,10,11-tetrahydro-9 H ,18 H -5,21:12,17-dimethenodibenzo e,k pyrrolo3,4- h1,4,13oxadiazacyclohexadecine-18,20(19 H)-dione, Ruboxistaurin (LY333531)."

The demonstrated role of PKC in the mediating amphetamine-stimulated dopamine efflux, which regulates amphetamine-induced dopamine transporter trafficking and activity, has promoted the research use of the selective, reversible PKC inhibitor (9 S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9 H,18 H-5,21:12,17-dimethenodibenzo[ e,k]pyrrolo[3,4- h][1,4,13]oxadiazacyclohexadecine-18,20(19 H)-dione, ruboxistaurin. Despite the interest in development of ruboxistaurin, as the mesylate monohydrate (Arxxant), for the treatment of diabetic retinopathy, macular oedema, and nephoropathy, several crucial details in physicochemical characterization were erroneous or missing. This report describes the synthesis and full characterization of ruboxistaurin free base (as a monohydrate), including X-ray crystallography to confirm the absolute configuration, and of the mesylate salt, isolated as a hydrate containing 1.5 moles of water per mole.


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This article was published in the following journal.

Name: ACS chemical neuroscience
ISSN: 1948-7193


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