19293-62-0Relevant articles and documents
Synthesis and biological evaluation of new C-10 substituted dithranol pleiotropic hybrids
Bariamis, Stavros E.,Magoulas, George E.,Grafanaki, Katerina,Pontiki, Eleni,Tsegenidis, Theodore,Athanassopoulos, Constantinos M.,Maroulis, George,Papaioannou, Dionissios,Hadjipavlou-Litina, Dimitra
, p. 7251 - 7263 (2015)
Selective alkylation of the antipsoriatic drug dithranol (DTR) at C-10 with tert-butyl bromoacetate, followed by acid-mediated deprotection, produced the corresponding carboxylic acid 4 which was coupled with selectively protected polyamines (PAs), such as putrescine (PUT), spermidine (SPD) and spermine (SPM), dopamine and aliphatic amines and substituted benzylamines producing a series of DTR-PA hybrids, after acid-mediated deprotection, as well as simple amides. The compounds were tested as antioxidants and inhibitors of lipoxygenase (LOX). The amides 4,4′-dimethoxybenzhydrylamide 13 (86% and 95%), 2,4-dimethoxybenzylamide 12 (87% and 81%) and dodecylamide 9 (98% and 74%), and the hybrid DTR-SPM (7) (93% and 87%), showed the highest antioxidant activity in the DPPH and AAPH assays, whereas the most potent inhibitors of LOX were amide 13 (IC50 = 7 μM), the benzylamide 10 (IC50 = 7.9 μM) and the butylamide 8 (IC50 = 10 μM). Molecular binding studies showed that binding of these derivatives into the hydrophobic domain blocks approach of substrate to the active site, inhibiting soybean LOX. Amide 13 presented the highest anti-inflammatory activity (79.7%). The DTR moiety was absolutely necessary for securing high anti-inflammatory potency. Ethyl ester 3 (IC50 = 0.357 μM) and the amides 9 (IC50 = 0.022 μM) and 13 (IC50 = 0.56 μM) exhibited higher antiproliferative activity than DTR (IC50 = 0.945 μM) on HaCaT keratinocytes whereas amide 13 generally presented better cytocompatibility. Amide 13 is a very promising lead compound for further development as an anti-inflammatory and antiproliferative agent.
Hydrogen bond directed aerobic oxidation of amines via photoredox catalysis
Wang, Hongyu,Man, Yunquan,Wang, Kaiye,Wan, Xiuyan,Tong, Lili,Li, Na,Tang, Bo
supporting information, p. 10989 - 10992 (2018/10/08)
An application of H-bonding interactions for directing the α-C-H oxidation of amines to amides and amino-ketones catalyzed by an organic photocatalyst is reported. The high efficiency of this method is demonstrated by the aerobic oxidation of pyrrolidines, diarylamines and benzylamines bearing urea groups with high yields and a wide substrate scope.
Discovery of N-[Bis(4-methoxyphenyl)methyl]-4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamide (MK-8617), an Orally Active Pan-Inhibitor of Hypoxia-Inducible Factor Prolyl Hydroxylase 1-3 (HIF PHD1-3) for the Treatment of Anemia
Debenham, John S.,Madsen-Duggan, Christina,Clements, Matthew J.,Walsh, Thomas F.,Kuethe, Jeffrey T.,Reibarkh, Mikhail,Salowe, Scott P.,Sonatore, Lisa M.,Hajdu, Richard,Milligan, James A.,Visco, Denise M.,Zhou, Dan,Lingham, Russell B.,Stickens, Dominique,Demartino, Julie A.,Tong, Xinchun,Wolff, Michael,Pang, Jianmei,Miller, Randy R.,Sherer, Edward C.,Hale, Jeffrey J.
, p. 11039 - 11049 (2016/12/30)
The discovery of novel 4-hydroxy-2-(heterocyclic)pyrimidine-5-carboxamide inhibitors of hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD) is described. These are potent, selective, orally bioavailable across several species, and active in stimulati