- SMALL MOLECULES THAT TARGET THE RNA THAT CAUSES ALS
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Disclosed herein are compounds that selectively bind an expanded transcribed repeat r(G4C2)exp, prevent sequestration of RNA-binding proteins, and inhibit translation of repeat associated non-ATG (RAN) translation responsible for generation of toxic dipeptide repeats underlying diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The compounds and their pharmaceutical compositions are useful in treating a disease or condition characterized by an expanded G4C2 repeat RNA (r(G4C2)exp), such as ALS and FTD.
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Paragraph 00107; 00110
(2022/04/03)
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- NOVEL TRIFLUOROMETHYL-OXADIAZOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISEASE
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The invention relates to novel trifluoromethyl-oxadiazole derivatives of formula (I), and pharmaceutically acceptable salts thereof, in which all of the variables are as defined in the specification, pharmaceutical compositions thereof, pharmaceutical com
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Page/Page column 50
(2013/06/27)
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- NOVEL TRIFLUOROMETHYL-OXADIAZOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISEASE
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The invention relates to novel trifluoromethyl-oxadiazole derivatives of formula (I), and pharmaceutically acceptable salts thereof, (I) in which all of the variables are as defined in the specification, pharmaceutical compositions thereof, pharmaceutical combinations thereof, and their use as medicaments, particularly for the treatment of neurodegeneration, muscle atrophy or metabolic syndrome via inhibition of HDAC4.
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Page/Page column 94
(2013/03/26)
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- Incorporation of basic side chains into cryptolepine scaffold: Structure-antimalarial activity relationships and mechanistic studies
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The synthesis of cryptolepine derivatives containing basic side-chains at the C-11 position and their evaluations for antiplasmodial and cytotoxicity properties are reported. Propyl, butyl, and cycloalkyl diamine side chains significantly increased activity against chloroquine-resistant Plasmodium falciparum strains while reducing cytotoxicity when compared with the parent compound. Localization studies inside parasite blood stages by fluorescence microscopy showed that these derivatives accumulate inside the nucleus, indicating that the incorporation of a basic side chain is not sufficient enough to promote selective accumulation in the acidic digestive vacuole of the parasite. Most of the compounds within this series showed the ability to bind to a double-stranded DNA duplex as well to monomeric hematin, suggesting that these are possible targets associated with the observed antimalarial activity. Overall, these novel cryptolepine analogues with substantially improved antiplasmodial activity and selectivity index provide a promising starting point for development of potent and highly selective agents against drug-resistant malaria parasites.
- Lavrado, Jo?o,Cabal, Ghislain G.,Prudêncio, Miguel,Mota, Maria M.,Gut, Jiri,Rosenthal, Philip J.,Díaz, Cecília,Guedes, Rita C.,Dos Santos, Daniel J. V. A.,Bichenkov?, Elena,Dougla?, Kenneth T.,Moreira, Rui,Paulo, Alexandra
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experimental part
p. 734 - 750
(2011/04/15)
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- An efficient and general synthesis of primary amines by ruthenium-catalyzed amination of secondary alcohols with ammonia
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Atom efficiency and selectivity are the key features of the first homogeneously catalyzed amination of secondary alcohols with ammonia to give the corresponding primary amines (see scheme). This novel amination method relies on the commercially available catalyst [Ru3(CO)12]/ cataCXium PCy and does not require any additional source of hydrogen.
- Imm, Sebastian,Neubert, Lorenz,Neumann, Helfried,Beller, Matthias
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supporting information; experimental part
p. 8126 - 8129
(2011/02/22)
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- Cryptolepine analogues containing basic aminoalkyl side-chains at C-11: Synthesis, antiplasmodial activity, and cytotoxicity
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A series of cryptolepine derivatives has been synthesized through the incorporation of short basic side-chains in the C-11 position of the 10H-indolo[3,2-b]quinoline scaffold. Their antiplasmodial activity was evaluated in vitro against the chloroquine resistant Plasmodium falciparum W2 strain, showing IC50 values between 22 and 184 nM, while their cytotoxicity was assessed using HUVEC cells, revealing three compounds with a selectivity ratio higher than 10. The most selective of these derivatives, 4d, with a selectivity ratio of 46, was also the least cytotoxic of the series.
- Lavrado, Joao,Paulo, Alexandra,Gut, Jiri,Rosenthal, Philip J.,Moreira, Rui
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p. 1378 - 1381
(2008/12/21)
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- Method of treating chloroquine-resistant malaria with aminoquinoline derivatives
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Novel aminoquinoline derivatives of the general formula STR1 are described. Also described are methods for the treatment of malaria pathogens, particularly chloroquine-resistance malaria pathogens with compounds of formula I or the pharmaceutically acceptable salts and hydrolyzable esters thereof.
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- Structure of a Peptidal Antibiotic P168 produced by Paecilomyces lilacinus (Thom) Samson
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The peptide antibiotic P168 contained a new amino acid, (2S,4S)-2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid (6) and an amine, (S)-N1,N1-dimethylpropane-1,2-diamine (4) along with other unusual amino acids.The structure of the peptide was determined as (I) by in-beam mass spectrometry.
- Isogai, Akira,Suzuki, Akinori,Tamura, Saburo,Higashikawa, Shizuo,Kuyama, Shimpei
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p. 1405 - 1411
(2007/10/02)
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- Structure of Leucinostatin A, New Peptide Antibiotic from Paecilomyces lilacinus A-267
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A new antibiotic leucinostatin A was isolated from the culture filtrate of Paecilomyces lilacinus A-267 and its structure was elucidated by mass spectrometric and degradative methods.
- Mori, Yuji,Tsuboi, Makoto,Suzuki, Makoto,Fukushima, Kazutaka,Arai, Tadashi
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