13989-82-7Relevant articles and documents
New quaternary ammonium oxicam derivatives: synthesis and in vitro antiosteoarthritis evaluation
Vidal, Aurelien,Chezal, Jean-Michel,Mounetou, Emmanuelle
, p. 405 - 410 (2010)
A series of new oxicam derivatives bearing a quaternary ammonium (QA) moiety was synthesized and evaluated in vitro for antiosteoarthritis properties. Propyltrimethyl ammonium 3 and propyldiethylmethyl ammonium 11 stimulated aggrecan expression and mitigated the inhibitory action of IL-1. QA derivative 3 also increased TGF-β2 and type II receptor expression. These results suggest that such derivatives may not only inhibit the osteoarthritis degradation process but also stimulate its regeneration. QA derivatives 3 and 11 offer potential for developing new therapeutic approaches to osteoarthritis treatment.
BENZYL SUBSTITUTED INDAZOLES
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Page/Page column 256; 257, (2016/04/10)
Compounds of formula (I) and their use as pharmaceuticals.
Regioselective covalent modification of hemoglobin in search of antisickling agents
Park, Soobong,Hayes, Brittany L.,Marankan, Fatima,Mulhearn, Debbie C.,Wanna, Linda,Mesecar, Andrew D.,Santarsiero, Bernard D.,Johnson, Michael E.,Venton, Duane L.
, p. 936 - 953 (2007/10/03)
Although the molecular defect in sickle hemoglobin that produces sickle cell disease has been known for decades, there is still no effective drug treatment that acts on hemoglobin itself. In this work, a series of diversely substituted isothiocyanates (R-NCS) were examined for their regioselective reaction with hemoglobin in an attempt to alter the solubility properties of sickle hemoglobin. Electrospray mass spectrometry, molecular modeling, X-ray crystallography, and conventional protein chemistry were used to study this regioselectivity and the resulting increase in solubility of the modified hemoglobin. Depending on the attached R-group, the isothiocyanates were found to react either with the Cysβ93 or the N-terminal amine of the α-chain. One of the most effective compounds in the series, 2-(N,N-dimethylamino)ethyl isothiocyanate, selectively reacts with the thiol of Cysβ93 which, in conjunction with the cationic group, was seen to perturb the local hemoglobin structure. This modified HbS shows an approximately 30% increase in solubility for the fully deoxygenated state, along with a significant increase in oxygen affinity. This compound and a related analogue appear to readily traverse the erythrocyte membrane. A discussion of the relation of these structural changes to inhibition of gelation is presented. The dual activities of increasing HbS oxygen affinity and directly inhibiting deoxy HbS polymerization, in conjunction with facile membrane traversal, suggest that these cationic isothiocyanates show substantial promise as lead compounds for development of therapeutic agents for sickle cell disease.
