65469-41-2Relevant articles and documents
Accepting the Invitation to Open Innovation in Malaria Drug Discovery: Synthesis, Biological Evaluation, and Investigation on the Structure-Activity Relationships of Benzo[b]thiophene-2-carboxamides as Antimalarial Agents
Pieroni, Marco,Azzali, Elisa,Basilico, Nicoletta,Parapini, Silvia,Zolkiewski, Michal,Beato, Claudia,Annunziato, Giannamaria,Bruno, Agostino,Vacondio, Federica,Costantino, Gabriele
supporting information, p. 1959 - 1970 (2017/03/17)
Malaria eradication is a global health priority, but current therapies are not always suitable for providing a radical cure. Artemisinin has paved the way for the current malaria treatment, the so-called Artemisinin-based Combination Therapy (ACT). However, with the detection of resistance to ACT, innovative compounds active against multiple parasite species and at multiple life stages are needed. GlaxoSmithKline has recently disclosed the results of a phenotypic screening of an internal library, publishing a collection of 400 antimalarial chemotypes, termed the “Malaria Box”. After analysis of the data set, we have carried out a medicinal chemistry campaign in order to define the structure-activity relationships for one of the released compounds, which embodies a benzothiophene-2-carboxamide core. Thirty-five compounds were prepared, and a description of the structural features responsible for the in vitro activity against different strains of P. falciparum, the toxicity, and the metabolic stability is herein reported.
Novel derivatives of pyridylbenzo[b]thiophene-2-carboxamides and benzo[b]thieno[2,3-c]naphthyridin-2-ones: minor structural variations provoke major differences of antitumor action mechanisms
Ester, Katja,Hranjec, Marijana,Piantanida, Ivo,?aleta, Irena,Jarak, Ivana,Paveli?, Kre?imir,Kralj, Marijeta,Karminski-Zamola, Grace
supporting information; experimental part, p. 2482 - 2492 (2010/03/01)
Novel cyano- and 2-imidazolinyl-substituted derivatives of pyridylbenzo[b]thiophene-2-carboxamides 4, 5, 10-13 and benzo[b]thieno[2,3-c] naphthyridin-2-ones 6, 7, 14-17 were prepared. All derivatives showed a prominent antiproliferative effect. Extensive DNA binding studies and additional biological evaluations point to various modes/targets of action. The results strongly support intercalation into DNA as a dominant binding mode of fused analogues, which was substantiated using topoisomerase I inhibition assay. Most intriguingly, only minor structural difference between "nonfused" compounds 12 and 13 has strong impact on the interactions with DNA; while 13 binds within the DNA minor groove in the form of dimer, 12 does not form significant interactions with DNA. The assumption that severe mitotic impairment (G2/M phase arrest) induced by 12 could point to tubulin, another important target, was confirmed by its obvious anti-tubulin activity observed in immunofluorescence assay, whereby treated cells showed disruption of microtubule formation comparable to the effect obtained by paclitaxel, a well-known tubulin antagonist chemotherapeutic.
Synthesis of Benzothienonaphthyridines
Kudo, Hirotaka,Takahashi, Kazufumi,Castle, Raymond N.,Lee, Milton L.
, p. 1009 - 1011 (2007/10/02)
3-Chlorobenzothiophene-2-carbonyl chloride reacted readily with 2-amino-, 3-amino, or 4-aminopyridine to give the corresponding amides.Photocyclization of the amides afforded the following lactams:benzothienonaphthyridin-6(5H)-one (14), benzothienonaphthyridin-6(5H)-one (7), benzothienonaphthyridin-6(5H)-one (11), and benzothienonaphthyridin-6(5H)-one (3).These lactams have been converted to other derivatives including in two instances the unsubstituted ring system.
