78957-20-7Relevant articles and documents
MATRIX METALLOPROTEINASE (MMP) INHIBITORS AND METHODS OF USE THEREOF
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Paragraph 0472-0473, (2019/12/02)
Hydantoin based compounds useful as inhibitors of matrix metalloproteinases (MMPs), particularly macrophage elastase (MMP-12) are described. Also described are related compositions and methods of using the compounds to inhibit MMP-12 and treat diseases mediated by MMP-12, such as asthma, chronic obstructive pulmonary disease (COPD), emphysema, acute lung injury, idiopathic pulmonary fibrosis (IPF), sarcoidosis, systemic sclerosis, liver fibrosis, nonalcoholic steatohepatitis (NASH), arthritis, cancer, heart disease, inflammatory bowel disease (IBD), acute kidney injury (AKI), chronic kidney disease (CKD), Alport syndrome, and nephritis.
Chemical insights in the concept of hybrid drugs: The antitumor effect of nitric oxide-donating aspirin involves a quinone methide but not nitric oxide nor aspirin
Hulsman, Niels,Medema, Jan Paul,Bos, Carina,Jongejan, Aldo,Leurs, Rob,Smit, Martine J.,De Esch, Iwan J. P.,Richel, Dick,Wijtmans, Maikel
, p. 2424 - 2431 (2008/02/03)
Hybrid drug 1 (NO-ASA) continues to attract intense research from chemists and biologists alike. It consists of ASA and a -ONO2 group connected through a spacer and is in preclinical development as an antitumor drug. We report that, contrary to current beliefs, neither ASA nor NO contributes to this antitumor effect. Rather, an unsubstituted QM was identified as the sole cytotoxic agent. QM forms from 1 after carboxylic ester hydrolysis and, in accordance with the HSAB theory, selectively reacts with cellular GSH, which in turn triggers cell death. Remarkably, a derivative lacking ASA and the -ONO 2 group is 10 times more effective than 1. Thus, our data provide a conclusive molecular mechanism for the antitumor activity of 1. Equally importantly, we show for the first time that a "presumed invisible" linker in a hybrid drug is not so invisible after all and is in fact solely responsible for the biological effect.
Dendroid peptide structural mimetics of ω-conotoxin MVIIA based on a 2(1H)-quinolinone core
Guo, Zhao-Xia,Cammidge, Andrew N.,Horwell, David C.
, p. 5169 - 5175 (2007/10/03)
Three mimetics of the peptide ω-Conotoxin MVIIA have been synthesised following the dendroid approach. The three key central amino acids of the natural peptide are mimicked by phenylguanidine (arginine), isopentyl (leucine) and aryl alcohol (tyrosine) att
