- Regioselective Functionalization of Chlorophthalazine Derivatives
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Chlorophthalazines were efficiently metalated using tmpZnClLiCl under microwave irradiation. This provided novel substituted phthalazine derivatives after subsequent trapping of the resulting organometallic reagents with various electrophiles. Moreover, Negishi cross-coupling reactions have been performed affording new polyfunctionalized phthalazine scaffolds in very good yields.
- Crestey, Francois,Knochel, Paul
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experimental part
p. 1097 - 1106
(2010/06/14)
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- PHTHALAZINE COMPOUNDS AS p38 MAP KINASE MODULATORS AND METHODS OF USE THEREOF
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The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A4, L, R1, R2, R3, R5 and m are as defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of p38 map kinase mediated diseases including rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disease, ankylosing spondylitis, pain and other inflammatory disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.
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Page/Page column 40
(2010/04/28)
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- Development of a practical synthesis of a p38 MAP kinase inhibitor
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A practical synthesis of the phthalazine-based p38 MAP kinase inhibitor [(S)-2] was needed for an ongoing program. Vibrational circular dichroism provided the assignment of the absolute stereochemistry of the target compound. The selected synthetic route
- Thiel, Oliver R.,Achmatowicz, Michal,Bernard, Charles,Wheeler, Philip,Savarin, Cecile,Correll, Tiffany L.,Kasparian, Annie,Allgeier, Alan,Bartberger, Michael D.,Tan, Helming,Larsen, Robert D.
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experimental part
p. 230 - 241
(2010/04/22)
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- Practical synthesis of a p38 MAP kinase inhibitor
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p38 MAP kinase inhibitors have attracted considerable interest as potential agents for the treatment of inflammatory diseases. Herein, we describe a concise and efficient synthesis of inhibitor 1 that is based on a phthalazine scaffold. Highlights of our approach include a practical synthesis of a 1,6-disubstituted phthalazine building block 24 as well as the one-pot formation of boronic acid 27. Significant synthetic work to understand the reactivity principles of the intermediates helped in selection of the final synthetic route. Subsequent optimization of the individual steps of the final sequence led to a practical synthesisof 1.
- Achmatowicz, Michal,Thiel, Oliver R.,Wheeler, Philip,Bernard, Charles,Huang, Jinkun,Larsen, Robert D.,Faul, Margaret M.
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experimental part
p. 795 - 809
(2009/06/20)
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- Phthalazine, aza- and diaza-phthalazine compounds and methods of use
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The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A1, A2, B, R1, R2, R3 and R4 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.
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Page/Page column 32
(2008/06/13)
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