- First Contact: 7-Phenyl-2-Aminoquinolines, Potent and Selective Neuronal Nitric Oxide Synthase Inhibitors That Target an Isoform-Specific Aspartate
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Inhibition of neuronal nitric oxide synthase (nNOS), an enzyme implicated in neurodegenerative disorders, is an attractive strategy for treating or preventing these diseases. We previously developed several classes of 2-aminoquinoline-based nNOS inhibitor
- Cinelli, Maris A.,Reidl, Cory T.,Li, Huiying,Chreifi, Georges,Poulos, Thomas L.,Silverman, Richard B.
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p. 4528 - 4554
(2020/05/05)
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- A Series of Analogues to the AT2R Prototype Antagonist C38 Allow Fine Tuning of the Previously Reported Antagonist Binding Mode
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We here report on our continued studies of ligands binding to the promising drug target angiotensin II type 2 receptor (AT2R). Two series of compounds were synthesized and investigated. The first series explored the effects of adding small subs
- Isaksson, Rebecka,Lindman, Jens,Wannberg, Johan,Sallander, Jessica,Backlund, Maria,Baraldi, Dhaniel,Widdop, Robert,Hallberg, Mathias,?qvist, Johan,Gutierrez de Teran, Hugo,Gising, Johan,Larhed, Mats
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p. 114 - 125
(2019/02/07)
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- ANTI-FIBROTIC COMPOUNDS
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Provided herein are anti-fibrotic compounds, in particular those of Formula (I), that inhibit the TGF-beta signaling pathway. Also provided are pharmaceutical compositions comprising the anti-fibrotic compounds, and methods of treating diseases or conditions associated with fibrosis, inflammation, and benign or malignant neoplastic diseases in a subject by administering a compound or composition described herein. (Formula (I))
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Paragraph 00354
(2018/08/26)
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- Cationic chalcone antibiotics. Design, synthesis, and mechanism of action
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This paper describes how the introduction of "cationic" aliphatic amino groups in the chalcone scaffold results in potent antibacterial compounds. It is shown that the most favorable position for the aliphatic amino group is the 2-position of the B-ring, in particular in combination with a lipophilic substituent in the 5-position of the B-ring. We demonstrate that the compounds act by unselective disruption of cell membranes. Introduction of an additional aliphatic amino group in the á-ring results in compounds that are selective for bacterial membranes combined with a high antibacterial activity against both Gram-positive and -negative pathogens. The most potent compound in this study (78) has an MIC value of 2 μM against methicillin resistant Staphylococus aureus.
- Nielsen, Simon F.,Larsen, Mogens,Boesen, Thomas,Sch?nning, Kristian,Kromann, Hasse
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p. 2667 - 2677
(2007/10/03)
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- Design and Synthesis of New Naphthalenic Derivatives as Ligands for 2-Iodomelatonin Binding Sites
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New melatonin-like agents were designed from the frameworks of 2,5-dimethoxyphenethylamine, an important structural moiety for the 5-HT receptor, and (2-methoxynaphthyl)ethylamine.The compounds were synthesized by classical methods and evaluated in binding assays with chicken brain membranes using 2-(125I>iodomelatonin as the radioligand.Preliminary studies on the series of N-acyl-disubstituted phenethylamines showed the favorable role of the methoxy group in the ortho position of the side chain on the affinity for the receptor ( Ki = 8 +/- 0.2 nM ) for N-propionamide (3o).This effect was confirmed in a series of the naphthalene derivatives, a bioisosteric moiety of the indole ring, and several potent ligands for melatonin binding sites were prepared such as N-propionamide (4b) ( Ki = 0.67 +/- 0.05 nM ) and N-cyclopropylformamide (Ki = 0.05 +/- 0.004 nM ( (4k).Structure-activity relationships are discussed with regard to melatonin and bioisosteric naphthalenic compound 2.The Ki value for 4b was affected to a similar extent to that of melatonin by GTP-γ-S or Mn2+ in competition experiments, suggesting an agonist profile for this compound.
- Langlois, Michel,Bremont, Beatrice,Shen, Shuren,Poncet, Annie,Andrieux, Jean,et al.
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p. 2050 - 2060
(2007/10/02)
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