170277-82-4Relevant academic research and scientific papers
Synthesis and Characterization of the Selective, Reversible PKCβ 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)
Lewin, Anita H.,Brieaddy, Larry,Deschamps, Jeffrey R.,Imler, Gregory H.,Mascarella, S. Wayne,Reddy, P. Anantha,Carroll, F. Ivy
, p. 246 - 251 (2018/09/25)
The demonstrated role of PKCβ in mediating amphetamine-stimulated dopamine efflux, which regulates amphetamine-induced dopamine transporter trafficking and activity, has promoted the research use of the selective, reversible PKCβ inhibitor (9S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-dimethenodibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-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.
Synthesis of a structural analogue of the repeating unit from streptococcus pneumoniae 19F capsular polysaccharide based on the cross-metathesis- selenocyclization reaction sequence
Ronchi, Paolo,Scarponi, Catalina,Salvi, Matteo,Fallarini, Silvia,Polito, Laura,Caneva, Enrico,Bagnoli, Luana,Lay, Luigi
, p. 5172 - 5183 (2013/07/26)
Pseudo-oligosaccharides have attracted much interest as scaffolds for the synthesis of sugar mimics endowed with very similar biological properties but structurally and synthetically simpler than their natural counterparts. Herein, the synthesis of pseudo-oligosaccharides using the cross-metathesis reaction between distinct sugar-olefins followed by intramolecular selenocyclization of the obtained heterodimer as key steps is first investigated. This methodology has been then applied to the preparation of structural analogues of the trisaccharide repeating unit from Streptococcus pneumoniae 19F. The inhibition abilities of the synthetic molecules were evaluated by a competitive ELISA assay using a rabbit polyclonal anti-19F serum.
Synthesis of amino-1,4-anhydro-D-pentitols and amino-1,5-anhydro-D-hexitols with the arabino configuration from (R)-glycidol
Aragones, Silvia,Bravo, Fernando,Diaz, Yolanda,Matheu, Ma. Isabel,Castillon, Sergio
, p. 1847 - 1856 (2007/10/03)
2-Amino-1,4-anhydro-pentitol and 3-amino-1,5-anhydro-4-deoxy-hexitol with the arabino configuration were synthesised from (R)-glycidol using a metathesis reaction as the key step. The dihydrofuran or dihydropyran products obtained after the metathesis rea
Enantioselective synthesis of syn- and anti-1,3-diols via allyltitanation of unprotected β-hydroxyaldehydes
BouzBouz, Samir,Cossy, Janine
, p. 501 - 504 (2007/10/03)
(Formula presented) Syn- or anti-1,3-diols units were synthesized with excellent diastereomeric excess from unprotected chiral β-hydroxyaldehydes by using an enantioselective allyltitanation.
Enantioselective allyltitanations. Synthesis of optically active 1,2- diol units: Useful intermediates for the preparation of biologically active compounds
Cossy, Janine,Bouzbouz, Samir,Caille, Jean Claude
, p. 3859 - 3862 (2007/10/03)
1,2-Diol units were synthesized with excellent enantiomeric excess by using an enantioselective allyltitanation of α-alkoxy-substituted aldehydes.
Macrocyclic bisindolylmaleimides: Synthesis by inter- and intramolecular alkylation
Faul, Margaret M.,Winneroski, Leonard L.,Krumrich, Christine A.,Sullivan, Kevin A.,Gillig, James R.,Neel, David A.,Rito, Christopher J.,Jirousek, Michael R.
, p. 1961 - 1973 (2007/10/03)
Macrocyclic bisindolylmaleimides 1-4 have been identified as competitive reversible inhibitors of PKC β1 and β2 and are being advanced to the clinic for evaluation as a treatment of retinopathy associated with diabetic complications. Highly convergent and stereoselective syntheses of 1-4 have been developed. The key synthetic step involves intermolecular alkylation of symmetrical bisindolylmaleimide 9 with chiral bisalkylating agent 8c and is amenable to the preparation of multikilogram quantities of these compounds. The synthetic sequence to 1, the most active the compound, proceeds in 11 steps and 26% overall yield (> 98% ee) from (R)-1-chloro-2,3-propanediol. No chromatographic purifications are required throughout the process and the final product is isolated in >97% purity after crystallization from DMF/MeOH. Synthesis of 1-4 by intramolecular alkylation proved less efficient, requiring 17 steps and affording 1-4 in lower overall yields of 6.0-8.5%.
Synthesis of bisindolylmaleimides
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, (2008/06/13)
The present invention provides a novel synthesis of the compounds of Formula (I): STR1 The compounds are produced in high yield and without utilizing expensive chromatographic separations. The synthesis is particularly advantageous because it is stereosel
