Synthesis and Characterization of the Selective, Reversible PKCß 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 (LY333531).
ACS Chem Neurosci
; 10(1): 246-251, 2019 01 16.
Article
em En
| MEDLINE
| ID: mdl-30156829
ABSTRACT
The demonstrated role of PKCß in mediating amphetamine-stimulated dopamine efflux, which regulates amphetamine-induced dopamine transporter trafficking and activity, has promoted the research use of the selective, reversible PKCß inhibitor (9 S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9 H,18 H-5,2112,17-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 edema, 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 mol of water per mole.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Química Farmacêutica
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Inibidores Enzimáticos
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Proteína Quinase C beta
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Indóis
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Maleimidas
Idioma:
En
Revista:
ACS Chem Neurosci
Ano de publicação:
2019
Tipo de documento:
Article