- 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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- Construction of Heteroacenes with Fused Thiophene and Pyrrole Rings via the Fischer Indolization Reaction
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A convenient approach to ladder-type 6H-benzo[4′,5′]thieno[2′,3′:4,5]thieno[3,2-b]indoles bearing various substituents in both terminal benzene rings has been developed. The protocol suggested for preparing these N,S-heteroacenes is based on using easily
- Irgashev, Roman A.,Karmatsky, Arseny A.,Rusinov, Gennady L.,Charushin, Valery N.
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supporting information
p. 804 - 807
(2016/03/01)
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- Synthesis, characterization and structure activity relationship studies of benzo[b]thiophene derivatives as promising class of antimicrobial agents
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Here we employed simple chemistry for the synthesis of a new potent series of benzo[b]thiophene containing 2-carbonylchlorides (1), 2-isopropyl carboxamides (2), 2-(piperidin-1-yl)-methanones (3) by nucleophilic chloro cyclocondensation of substituted-cin
- Ghodasara,Vaghasiya,Gothaliya,Shah
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p. 349 - 354
(2014/03/21)
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- PIPERIDIN-4-YL-AZETIDINE DIAMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS
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Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds, and enantiomers, diastereomers, and pharmaceutically acceptable salts thereof, are represented by Formula (I) as follows: wherein Y, Z, and R are defined herein.
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Paragraph 0299; 0300
(2013/05/08)
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- The Synthesis of Difluorobenzothienoquinolines and Their N-Methyl Quaternary Salts
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A series of difluorobenzothienoquinolines has been prepared by photocyclization of the appropriate carboxamides.The lactams obtained were converted into the corresponding chloro derivatives which were catalytically dechlorinated into the difluorobenzothienoquinolines.The latter compounds were transformed into the N-methyl quaternary salts.
- Luo, Jiann-Kuan,Castle, Steven L.,Castle, Raymond N.
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p. 2047 - 2052
(2007/10/02)
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- Sythesis of substituted Benzothiophenes
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Cyclization of the cinnamic acids 1a-t and their derivatives 1u,1v, and 1w with thionyl chloride affords the benzothiophenes 2a-t and 2v,w, respectively. 2a and 2v,w have been also prepared in an independent way from the corresponding alkynes and disulfur dichloride.
- Ried, Walter,Oremek, Gerhard,Ocakcioglu, Belkis
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p. 1424 - 1427
(2007/10/02)
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