- 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
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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.
- Pieroni, Marco,Azzali, Elisa,Basilico, Nicoletta,Parapini, Silvia,Zolkiewski, Michal,Beato, Claudia,Annunziato, Giannamaria,Bruno, Agostino,Vacondio, Federica,Costantino, Gabriele
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p. 1959 - 1970
(2017/03/17)
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- NOVEL COMPOUNDS AND THEIR USE IN THERAPY
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The invention provides compounds which inhibit N-myristoyltransferase and are selective for protozoal N-myristoyltransferase and, consequently suitable to treat microbial infections, including viral and fungal infections, and protozoan infections such as malaria, leishmaniasis and sleeping sickness.
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Page/Page column 68
(2013/06/27)
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- Discovery of novel and ligand-efficient inhibitors of plasmodium falciparum and plasmodium vivax N-myristoyltransferase
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N-Myristoyltransferase (NMT) is an attractive antiprotozoan drug target. A lead-hopping approach was utilized in the design and synthesis of novel benzo[b]thiophene-containing inhibitors of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) NMT. These inhibitors are selective against Homo sapiens NMT1 (HsNMT), have excellent ligand efficiency (LE), and display antiparasitic activity in vitro. The binding mode of this series was determined by crystallography and shows a novel binding mode for the benzothiophene ring.
- Rackham, Mark D.,Brannigan, James A.,Moss, David K.,Yu, Zhiyong,Wilkinson, Anthony J.,Holder, Anthony A.,Tate, Edward W.,Leatherbarrow, Robin J.
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supporting information
p. 371 - 375
(2013/02/23)
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- As many as six tandem reactions in one step! Unprecedented formation of highly functionalized benzothiophenes
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A novel reaction pathway involving 1,3-diketones and 2,2′- dithiodibenzoylchloride that gives access to benzothiophenes with spiroketal, lactone, carbonyl, hydroxyl and carboxylic acid functionalities is discussed. The Royal Society of Chemistry 2009.
- Gopinath, Pushparathinam,Nilaya, Surapaneni,Debi, Tripathy Ranjan,Ramkumar, Venkatachalam,Muraleedharan, Kannoth Manheri
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supporting information; experimental part
p. 7131 - 7133
(2010/03/25)
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- A simple route to benzo[b]thiophenes: Sulfanylation-acylation of C-H acids with 2-(chlorosulfanyl)benzoyl chloride
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A convenient procedure for the preparation of 2,2-disubstituted benzo[b]thiophen3(2H)-ones and 2-substituted 3-hydroxybenzo[b]thiophenes from β-diketones, β-keto- and β-cyanoesters, and β-cyanoketones, diethyl malonate, malonitrile, and anthrone has been
- Mlochowski, Jacek,Potaczek, Piotr
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experimental part
p. 1115 - 1123
(2010/03/01)
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- ANTIDIABETIC COMPOUNDS COMPRISING BENZOFURAN AND BENZOTHIOPHENE DERIVATIVES
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The invention relates to compounds of the general formula (I) in which R1, R2, R3, R4, R5, R6 and X are as defined in Claim 1. These compounds can be used in the treatment of pathologies associated with insulin resistance syndrome.
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Page/Page column 22
(2010/02/12)
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- Rhodium carbenoid mediated cyclisations. Part 6. Synthesis of cyclic sulphoxonium ylides
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Treatment of diazo sulphoxides with rhodium(11) acetate gives stable five- and six- membered cyclic sulphoxonium ylides.
- Moody, Christopher J.,Taylor, Roger J.
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p. 6525 - 6544
(2007/10/02)
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- Synthesis of 4,10-dihydro-4,10-dioxo-1H[1]benzothiopyrano[3,2-b]pyridine and 7-oxo-7,13-dihydro[1]benzothiopyrano[2,3-b]-1,5-benzodiazepine
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3-Amino-4H-1-benzothiopyran-4-one (3-aminothiochromone) was easily prepared by reaction of 3-bromothiochromen-4-one with sodium azide in methanol-water. Condensation of 3-aminothiochromone with diethyl ethoxymethylenemalonate and with dimethyl acetylenedicarboxylate gave intermediates, which were thermally cyclized to give 4,10-dihydro-4,10-doxo-1H[1]benzothiopyrano[3,2-b]pyridinecarboxylates. 3-Formyl-thiochromone was condensed with o-phenylenediamine to give 7-oxo-7,13-dihydro[1]benzothiopyrano[2,3-b]-1,5-benzodiazepine.
- Nakazumi,Endo,Nakaue,Kitao
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