13210-52-1Relevant articles and documents
7-Azacinnolin-4(1H)-one preparation and NMR studies of tautomery
Stockmann, Vegar,Primpke, Sebastian,Fiksdahl, Anne
, p. 737 - 741 (2011)
As part of our current investigations of nitropyridines, we hereby report the preparation of a new annulated heterocycle by C-azo coupling. Thus, the azacinnoline, pyrido[3,4-c]pyridazin-4(1H)-one (38%), was prepared from 4-acetyl-3-aminopyridine via diazotization. 1H, 13C, and 15N NMR spectroscopic investigations revealed that the azacinnoline exclusively exists in the NH-keto tautomeric form in DMSO-d6, CD 3OD, and D2O.
Synthesis of novel 1,7-naphthyridines by Friedlaender condensation of pyridine substrates
Stockmann, Vegar,Fiksdahl, Anne
scheme or table, p. 1383 - 1387 (2012/01/05)
The general ability of appropriate pyridyl compounds (aldehyde or ketone) to undergo Friedlaender condensation to give different 1,7-naphthyridines has been demonstrated. 2,4-Disubstituted 1,7-naphthyridine 8 was prepared from 3-amino-4-acetylpyridine (6) and ketone 4 (82%). The Friedlaender self-condensation of pyridyl substrate 6 is reported, as well. The dimer product, 2-(3-aminopyridin-4-yl)-4-methyl-1,7-naphthyridine (7), was obtained in 97% yield. 2-Aryl-and 2,3-diaryl-1,7-naphthyridines (16-18) were prepared from 3-aminoisonicotinaldehyde (13) and arylketones 4, 14, and 15 (28-71%). The key substrates 6 and 13 are readily available via the improved pyridine nitration method. Copyright
Synthesis, Topoisomerase I Inhibitory Activity, and in Vivo Evaluation of 11-Azacamptothecin Analogs
Uehling, David E.,Nanthakumar, Suganthini S.,Croom, Dallas,Emerson, David L.,Leitner, Peter P.,et al.
, p. 1106 - 1118 (2007/10/02)
A series of analogs based on a novel template, 11-aza-(20S)-camptothecin, were obtained from total synthesis and tested as potential anticancer drugs in the topoisomerase I enzyme cleavable complex assay.The parent compound 11-aza-(20S)-camptothecin (8) was derived from a Friedlander condensation between the known aminopyridine derivative 3-(3-amino-4-picolylidene)-p-toluidyne and optically active tricyclic ketone 7.Compound 8 had activity approximately twice that of (20S)-camptothecin in the calf thymus topoisomerase I cleavable complex assay.Compounds were prepared wherein the 11-aza nitrogen atom was quaternized as either the corresponding N-oxide or methyl iodide.Compounds with quaternized N-11 showed improved water solubility and were equipotent to the clinically investigated camptothecin analog topotecan in the cleavable complex assay.These compounds were evaluated in vivo in nude mice bearing HT-29 human colon carcinoma xenografts.The analog 11-aza-(20S)-camptothecin 11-N-oxide was found to significantly retard tumor growth when compared to untreated controls.Finally 7,10-disubstituted 11-azacamptothecin analogs were synthesized using Pd(0) coupling reactions of 10-bromo-7-alkyl-11-aza-(20S)-camptothecins 19 and 20, which in turn were available from a Friedlander condensation of the novel bromopyridine derivatives 17a and 17b with 7.Among the 10-substituted series, a number of analogs displayed extremely high in vitro potency against topoisomerase I and improved aqueous solubility.A significant number of the compounds were found to be active in whole cell cytotoxicity assays and several were evaluated in nude mice bearing the HT-29 tumor xenografts.The most effective of these proved to be (S)-11-aza-7-ethyl-10-(aminohydroximinomethyl)camptothecin trifluoroacetic acid salt (27), a potent topoisomerase I inhibitor which demonstrated excellent efficacy in both short term and in extended in vivo assays.A comparison between in vitro enzyme data and in vivo data from nude mouse studies in other compounds in this series revealed a poor overall correlation between topoisomerase inhibition in vitro and antitumor efficacy in vivo.
