104317-54-6Relevant articles and documents
Synthesis and antischistosomal activity of linker- and thiophene-modified biaryl alkyl carboxylic acid derivatives
Peter Ventura, Alejandra M.,Haeberlein, Simone,Konopka, Leonie,Obermann, Wiebke,Grünweller, Arnold,Grevelding, Christoph G.,Schlitzer, Martin
, (2021/09/18)
Schistosomiasis is a neglected tropical disease caused by blood flukes of the genus Schistosoma and causes severe morbidity in infected patients. In 2018, 290.8 million people required treatment, and 200,000 deaths are reported per year. Treatment of this disease depends on a single drug, praziquantel (PZQ). However, in the past few years, reduced sensitivity of the parasites toward PZQ has been reported. Therefore, there is an urgent need for new drugs against this disease. In the past few years, we have focused on a new substance class called biaryl alkyl carboxylic acid derivatives, which showed promising antischistosomal activity in vitro. Structure–activity relationship (SAR) studies of the carboxylic acid moiety led to three promising carboxylic amides (morpholine, thiomorpholine, and methyl sulfonyl piperazine) with an antischistosomal activity down to 10 μM (morpholine derivative) and no cytotoxicity up to 100 μM. Here, we show our continued work on this substance class. We investigated, in extended SAR studies, whether modification of the linker and the thiophene ring could improve the antischistosomal activity. We found that the exchange of the alkyl linker by a pentadienyl or benzyl linker was tolerated and led to similar antischistosomal effects, whereas the exchange of the thiophene ring was not tolerated. Our data suggest that the thiophene ring is important for the antischistosomal activity of this compound class.
Pharmaceutical compounds comprising polyamines substituted with electron-affinic groups
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, (2008/06/13)
A compound or a salt thereof comprising a polyamine containing at least 2 electron-affinic groups is provided. In a preferred embodiment, the polyamine compound has the structure: wherein: A is a spacer; R1, R2, R3, and R4 are independently hydrogen, hydrocarbon, heterosubstituted hydrocarbon, heteroaryl, heterosubstituted heteroaryl, or an electron-affinic group containing substituent; and the compound contains at least one tertiary amine functionality having three substituents each of which independently contain at least one electron-affinic group or hydrophilic group.
Synthesis and in Vitro Evaluation of New Cephalosporins Exhibiting Antimicrobial Activity Against Gram-Positive Bacteria, in Particular Methicillin-Resistant Staphylococci
Lin, Ho-Shen,Rampersaud, Ashraff A.,Flokowitsch, Jane E.,Alborn, William E.,Wu, Ernie C. Y.,Preston, David A.
, p. 833 - 846 (2007/10/03)
The preparation and biological evaluation of 7β-acetamido>cephalosporins and 7β-acetamido>cephalosporins, 9a-o, substituted at the 3-position with acetyloxymethyl, chlorine, hydrogen, and methyl are described.Hantzsch's thiazole synthesis is employed to provide thiazoleacetic acids 5a-e, subsequently followed by Morpho CDI-assisted amidation to complete the synthesis of target cephalosporins 9a-o.These compounds display activity selectively against Gram-positive bacteria, but are inactive against most Gram-negative bacteria tested.Those with acetyloxymethyl at the 3-position, i.e., 9a, 9e, 9i, 9m, and 9o, exhibit activity with minimal inhibitory concentrations of 16 μg/mL or lower against four strains of methicillin-resistant staphylococci, namely Staphylococcus aureus X400 and S13E and Staphylococcus epidermidis 270 and 222.Notably, 9a displays an activity profile similar to that of vancomycin regarding its spectrum and potency.Key Words: Gram-positive bacteria; Methicillin-resistant staphylococci; Cephalosporin; Thiazole synthesis; Amidation.
