- MATRIX METALLOPROTEINASE (MMP) INHIBITORS AND METHODS OF USE THEREOF
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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.
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Paragraph 0472-0473
(2019/12/02)
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- Selective acylation of the phenolic hydroxyl of (hydroxyalkyl)phenols by using vinyl carboxylates as acyl donors in the presence of rubidium fluoride
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Highly selective acylation of the phenolic hydroxy group can be achieved with (hydroxyalkyl)phenols carrying both alcoholic and phenolic hydroxyls by the use of vinyl carboxylates as acyl donors in the presence of rubidium fluoride.
- Miyazawa, Toshifumi,Yamamoto, Masato,Danjo, Hiroshi
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p. 1351 - 1354
(2013/10/01)
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- 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
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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.
- Hulsman, Niels,Medema, Jan Paul,Bos, Carina,Jongejan, Aldo,Leurs, Rob,Smit, Martine J.,De Esch, Iwan J. P.,Richel, Dick,Wijtmans, Maikel
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p. 2424 - 2431
(2008/02/03)
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- ANTIBACTERIAL AGENTS
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Compounds of formula (I) have antibacterial activity wherein R represents hydrogen or 1, 2 or 3 optional substituents; W is =C(R1)- or =N-; R1 is hydrogen or an optional substituent and R2 is hydrogen, methyl, or fluorine; or R1 and R2 taken together are -CH2-, -CH2CH2-, -O-, or, in either orientation, -O- CH2- Or -OCH2CH2-; R3 is a radical of formula -(Alk1)m-(Z)p-(Alk2)n-Q wherein m, p and n are independently 0 or 1, provided that at least one of m, p and n is 1, Z is -O-, -S-, -S(O)-, -S(O2)-, -NH-, -N(CH3)-, -N(CH2CH3)-, -C(=O)-, -O-(C=O)-, -C(=O)-O-, or an optionally substituted divalent monocyclic carbocyclic or heterocyclic radical having 3 to 6 ring atoms; or an optionally substituted divalent bicyclic heterocyclic radical having 5 to 10 ring atoms; Alk1 and Alk2 are optionally substituted C1C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene radicals, which may optionally terminate with or be interrupted by -O-, -S-, -S(O)-, -S(O2)-, -NH-, -N(CH3)-, or -N(CH2CH3)-; and Q is hydrogen, halogen, nitrile, or hydroxyl or an optionally substituted monocyclic carbocyclic or heterocyclic radical having 3 to 6 ring atoms; or an optionally substituted bicyclic heterocyclic radical having 5 to 10 ring atoms.
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Page/Page column 77
(2010/11/28)
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- Dendroid peptide structural mimetics of ω-conotoxin MVIIA based on a 2(1H)-quinolinone core
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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
- Guo, Zhao-Xia,Cammidge, Andrew N.,Horwell, David C.
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p. 5169 - 5175
(2007/10/03)
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- Thiadiazole derivatives for the treatment of depressive states
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Thiadiazole derivatives of general formula (I) wherein R1 is selected from the class consisting of: C1-C10 linear or branched alkyl, benzyl, optionally substituted at the aromatic ring with one or more groups se
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- SELECTIVE REDUCTION OF ALDEHYDES IN PRESENCE OF A KETONE WITH CHLOROTRIMETHYLSILANE AND NICKEL BORIDE
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It has been shown that a combination of chlorotrimethylsilane and nickel boride effects the chemoselective reduction of an aldehyde in presence of a ketonic carbonyl group.
- Borbaruah, M.,Barua, N. C.,Sharma, R. P.
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p. 5741 - 5742
(2007/10/02)
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