- Harnessing Cascade Suzuki-Cyclization Reactions of Pyrazolo[3,4-b]pyridine for the Synthesis of Tetracyclic Fused Heteroaromatics
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Numerous procedures have been described for the functionalization of pyrazolo[3,4-b]pyridine, mainly involving nucleophilic substitutions at the C-4 position or esterifications/amidations at the C-5 position. In this paper, we describe a robust, easy to implement protocol for the Suzuki cross-coupling reaction of chloroarene 2, followed by in-situ lactonization to provide chromenopyrazolopyridines. The extension of the scope of the reaction to fused naphthyridinones is also reported. This strategy gave access to 10 original pyrazolopyridine-containing tetracyclic compounds.
- Lavrard, Hubert,Popowycz, Florence
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- Synthesis, topoisomerase-targeting activity and growth inhibition of lycobetaine analogs
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The plant alkaloid lycobetaine has potent topoisomerase-targeting properties and shows anticancer activity. Based on these findings, several lycobetaine analogs were synthesized mainly differing in their substituents at 2, 8 and 9 position and their biological activities were evaluated. The topoisomerase-targeting properties and cytotoxicity of these structural analogs were assessed in the human gastric carcinoma cell line GXF251L. Performing a plasmid relaxation assay, an increased inhibition of topoisomerase I was found with N-methylphenanthridinium chlorides bearing a 8,9-methylenedioxy moiety or a methoxy group in 2-position. Furthermore, quaternized phenanthridinium derivatives bearing either a 2-methoxy or a 8,9-methylenedioxy moiety in conjunction with a 2-hydroxy or 2-methoxy group display potent topoisomerase II inhibition as shown by decatenation of kinetoplast DNA. In general, the N-methylphenanthridinium chlorides possess more potency in inhibiting topoisomerase I than topoisomerase II. All quaternized derivatives also exhibited potent inhibition of tumor cell growth in the low micromolar concentration range. Hence, N-methylphenanthridinium compounds were found to represent a promising class of compounds, potently inhibiting both, topoisomerases I and II, and may be further developed into clinically useful topoisomerase inhibitors.
- Baechler, Simone A.,Fehr, Markus,Habermeyer, Michael,Hofmann, Andreas,Merz, Karl-Heinz,Fiebig, Heinz-Herbert,Marko, Doris,Eisenbrand, Gerhard
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supporting information
p. 814 - 823
(2013/02/25)
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- Small molecule thienopyrimidine-based protein tyrosine kinase inhibitors
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Various thienopyrimidine-based analog compounds are able to selectively inhibit the Src family of tyrosine kinases. These compounds are useful in the treatment of various diseases including hyperproliferative diseases, hematologic diseases, osteoporosis, neurological diseases, autoimmune diseases, allergic/immunological diseases, or viral infections.
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Page/Page column 40
(2010/02/15)
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- Imidazoline derivatives as alpha-1A adrenoceptor ligands
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Compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof are disclosed. Such compounds are useful in the treatment of Alpha-1A mediated diseases or conditions such as urinary incontinence.
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Page/Page column 30
(2010/02/11)
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- Dipeptides which promote release of growth hormone
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Compounds of formula (I) are growth hormone releasing peptide mimetics which are useful for the treatment and prevention of osteoporosis. STR1
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- PYRAZOLE DERIVATIVES AS ANGIOTENSIN II ANTAGONISTS
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Compounds of general formula I and their salts and solvates are angiotensin II receptor antagonists and as such are useful in the treatment of hypertension, congestive heart failure and elevated intraocular pressure. Pharmaceutical compositions including these compounds and processes for their preparation are also provided.
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