- DNDI-6148: A Novel Benzoxaborole Preclinical Candidate for the Treatment of Visceral Leishmaniasis
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Visceral leishmaniasis (VL) is a parasitic disease endemic across multiple regions of the world and is fatal if untreated. Current therapies are unsuitable, and there is an urgent need for safe, short-course, and low-cost oral treatments to combat this ne
- Bello, Davide,Braillard, Stéphanie,Caljon, Guy,Carvalho, Sandra,Corpas-Lopez, Victoriano,Freund, Yvonne,Gilbert, Ian H.,Glossop, Paul A.,Jacobs, Robert T.,Lukac, Iva,Maes, Louis,Mowbray, Charles E.,Nare, Bakela,Pandi, Bharathi,Patterson, Stephen,Speake, Jason,Van Den Kerkhof, Magali,Wall, Richard J.,Whitlock, Gavin A.,Wyllie, Susan,Yardley, Vanessa,Zuccotto, Fabio
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supporting information
p. 16159 - 16176
(2021/11/16)
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- New Series of Potent Allosteric Inhibitors of Deoxyhypusine Synthase
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Deoxyhypusine synthase (DHPS) is the primary enzyme responsible for the hypusine modification and, thereby, activation of the eukaryotic translation initiation factor 5A (eIF5A), which is key in regulating the protein translation processes associated with tumor proliferation. Although DHPS inhibitors could be a promising therapeutic option for treating cancer, only a few studies reported druglike compounds with this inhibition property. Thus, in this work, we designed and synthesized a new chemical series possessing fused ring scaffolds designed from high-throughput screening hit compounds, discovering a 5,6-dihydrothieno[2,3-c]pyridine derivative (26d) with potent inhibitory activity; furthermore, the X-ray crystallographic analysis of the DHPS complex with 26d demonstrated a distinct allosteric binding mode compared to a previously reported inhibitor. These findings could be significantly useful in the functional analysis of conformational changes in DHPS as well as the structure-based design of allosteric inhibitors.
- Tanaka, Yuta,Kurasawa, Osamu,Yokota, Akihiro,Klein, Michael G.,Saito, Bunnai,Matsumoto, Shigemitsu,Okaniwa, Masanori,Ambrus-Aikelin, Geza,Uchiyama, Noriko,Morishita, Daisuke,Kimura, Hiromichi,Imamura, Shinichi
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supporting information
p. 1645 - 1652
(2020/09/15)
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- Opioid receptor agonists and application thereof
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The invention discloses compounds and salts thereof that can be used as opioid receptor ligands, a preparation method of the compounds, compositions containing the compounds, and a use of the compounds as [mu] opioid receptor agonists; the compounds are used for treatment of [mu] opioid receptor-mediated related diseases, such as pains and pain-related disorders.
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Paragraph 2141; 2144-2148
(2019/01/24)
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- Regioselective and efficient halogenation of 4,5-unsubstituted alkyl 3-hydroxypyrrole/3-hydroxythiophene-2-yl-carboxylates
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Substituted heterocycles, such as pyrrole and thiophene, are commonly found in the field of pharmaceutical and material sciences. Here we studied the reactivity of 4,5-unsubstituted alkyl 3-hydroxypyrrol-2-yl-carboxylates and 4,5-unsubstituted alkyl 3-hydroxythiophen-2-yl-carboxylates in different halogenation conditions, due to their interest as building blocks in the synthesis of bioactive compounds and materials. We describe herein the regioselective monohalogenation of 3-hydroxypyrroles and 3-hydroxythiophenes in mild conditions with common halogenation agents. The selectivity of the halogenation was studied. Optimized one-step reaction conditions were found for monobromination and monochlorination. Finally, we observed that bromination with N-bromosuccinimide (NBS) took place at the C4 position of the heterocycle, while chlorination with SO2Cl2 led to C5-halogenated derivatives.
- Castillo-Aguilera, Omar,Depreux, Patrick,Halby, Ludovic,Azaroual, Nathalie,Arimondo, Paola B.,Goossens, Laurence
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p. 2537 - 2541
(2017/06/13)
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- 3-Alkoxy-4-bromothiophenes: General synthesis of monomers and regio-selective preparation of two dimers
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3-Alkoxy-4-bromothiophenes were synthesized in three steps from the readily available methyl 2-carboxylate-3-hydroxythiophene and two isomers of bithiophenes based on the 3-bromo-4-methoxythiophene moiety were regio-selectively prepared.
- Savitha, Gurunathan,Hergué, Noémie,Guilmet, Erwan,Allain, Magali,Frère, Pierre
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supporting information; experimental part
p. 1288 - 1291
(2011/03/22)
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- Synthesis of functionalized hydroxy-thiophene motifs as amido- and sulfonamido-phenol bioisosteres
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Novel highly substituted hydroxy thiophene motifs were designed and synthesized as viable amido phenol and sulfonamido phenol bioisosteres. Hydroxy group-directed regioselective bromination and palladium-catalyzed amination of thienyl bromide via Buckwald
- Chao, Jianhua,Taveras, Arthur G.,Aki, Cynthia J.
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scheme or table
p. 5005 - 5008
(2009/12/01)
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- N-([1,2,4] triazoloazinyl) thiophenesulfonamide compounds and their use as herbicides
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N-(Triazoloazinyl)thiophenesulfonamide compounds were prepared from appropriately substituted 2-amino[1,2,4]triazolo[1,5-c]pyrimidine, 2-amino[1,2,4]triazolo[1,5-a]pyrimidine and 2-amino[1,2,4]triazolo[1,5-a]pyridine compounds and appropriately substituted thiophenesulfonyl chloride compounds. The compounds were found to be useful as herbicides.
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- N-1H-tetrazol-5-yl-2-thiophene carboxamides, N-1H-tetrazol-5-yl-2-pyrrole carboxamides, N-1H-tetrazol-5-yl-2-furan carboxamides, and anti-allergic and anti-inflammatory use thereof
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The present invention is for compounds having the formula of N-1H-tetrazol-5-yl-2-thiophenecarboxamides, N-1H-tetrazol-5-yl-2-pyrrolecarboxamides, N-1H-tetrazol-5-yl-2-furancarboxamides or analogs of each of the carboxamides. The compounds are useful for the treatment of allergic or inflammatory conditions or diseases. Thus, pharmaceutical compositions and methods of use are also the invention. Processes of preparation for the compounds are also the invention.
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