- Discovery and Optimization of a Compound Series Active against Trypanosoma cruzi, the Causative Agent of Chagas Disease
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Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in South and Central America and recently has been found in other parts of the world, due to migration of chronically infected patients. The current treatment for Chagas disease is not satisfactory, and there is a need for new treatments. In this work, we describe the optimization of a hit compound resulting from the phenotypic screen of a library of compounds against T. cruzi. The compound series was optimized to the level where it had satisfactory pharmacokinetics to allow an efficacy study in a mouse model of Chagas disease. We were able to demonstrate efficacy in this model, although further work is required to improve the potency and selectivity of this series.
- Harrison, Justin R.,Sarkar, Sandipan,Hampton, Shahienaz,Riley, Jennifer,Stojanovski, Laste,Sahlberg, Christer,Appelqvist, Pia,Erath, Jessey,Mathan, Vinodhini,Rodriguez, Ana,Kaiser, Marcel,Pacanowska, Dolores Gonzalez,Read, Kevin D.,Johansson, Nils Gunnar,Gilbert, Ian H.
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p. 3066 - 3089
(2021/06/14)
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- Heterogeneous Catalytic Reductive Amination of Carbonyl Compounds with Ni-Al Alloy in Water as Solvent and Hydrogen Source
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The heterogeneous catalytic reductive amination of carbonyl compounds has been achieved by reactions of ammonium hydroxide and various amines with ketones and aldehydes. The process is based on the application of Raney type Ni-Al alloy in an aqueous medium. The reaction of the carbonyl compounds with the amine provided the corresponding Schiff bases that immediately underwent a reduction to provide primary and secondary amines as products. The controlled reaction of the Al content of the alloy with the solvent water generates hydrogen, and the in situ formed Raney Ni serves as a hydrogenation catalyst. The method is a simple and efficient way of preparing a broad variety of primary and secondary amines.
- Sch?fer, Christian,Ni?anci, Bilal,Bere, Matthew P.,Da?tan, Arif,T?r?k, Béla
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p. 3127 - 3133
(2016/09/09)
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- INDOLE CARBOXAMIDE DERIVATIVES AND USES THEREOF
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A compound of Formula (I) is provided that has been shown to be useful for treating a disease, disorder or syndrome that is mediated by the transportation of essential molecules in the mmpL3 pathway: (I) wherein R1, R2, R3, R4, R5 and R6 are as defined herein.
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Page/Page column 33
(2014/03/26)
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- HYDROXYETHYLAMINE DERIVATIVES FOR THE TREATMENT OF ALZHEIMER'S DISEASE
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The present invention relates to novel hydroxyethylamine compounds of formula (I): (I) having Asp2 (-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated-amyloid levels or-amyloid deposits, particularly Alzheimer's disease.
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