851859-50-2Relevant academic research and scientific papers
Accessible chiral linker to enhance potency and selectivity of neuronal nitric oxide synthase inhibitors
Jing, Qing,Li, Huiying,Roman, Linda J.,Martasek, Pavel,Poulos, Thomas L.,Silverman, Richard B.
, p. 56 - 60 (2014)
The three important mammalian isozymes of nitric oxide synthase (NOS) are neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). Inhibitors of nNOS show promise as treatments for neurodegenerative diseases. Eight easily synthesized compounds containing either one (20a,b) or two (9a-d; 15a,b) 2-amino-4-methylpyridine groups with a chiral pyrrolidine linker were designed as selective nNOS inhibitors. Inhibitor 9c is the best of these compounds, having a potency of 9.7 nM and dual selectivity of 693 and 295 against eNOS and iNOS, respectively. Crystal structures of nNOS complexed with either 9a or 9c show a double-headed binding mode, where each 2-aminopyridine headgroup interacts with either a nNOS active site Glu residue or a heme propionate. In addition, the pyrrolidine nitrogen of 9c contributes additional hydrogen bonds to the heme propionate, resulting in a unique binding orientation. In contrast, the lack of hydrogen bonds from the pyrrolidine of 9a to the heme propionate allows the inhibitor to adopt two different binding orientations. Both 9a and 9c bind to eNOS in a single-headed mode, which is the structural basis for the isozyme selectivity.
2-Aminopyridine-based Selective Neuronal Nitric Oxide Synthase Inhibitors
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Paragraph 0026; 0027, (2014/09/29)
Aminopyridine compounds, as can be used in conjunction with methods for modulation of nitric oxide synthase activity.
Discovery of novel 1-azoniabicyclo[2.2.2]octane muscarinic acetylcholine receptor antagonists
Lainé, Dramane I.,McCleland, Brent,Thomas, Sonia,Neipp, Christopher,Underwood, Brian,Dufour, Jeremy,Widdowson, Katherine L.,Palovich, Michael R.,Blaney, Frank E.,Foley, James J.,Webb, Edward F.,Luttmann, Mark A.,Burman, Miriam,Belmonte, Kristen,Salmon, Michael
supporting information; experimental part, p. 2493 - 2505 (2010/03/04)
A novel 4-hydroxyl(diphenyl)methyl substituted quinuclidine series was discovered as a very promising class of muscarinic antagonists. The structure-activity relationships of the connectivity of the diphenyl moiety to the quinuclidine core and around the ring nitrogen side chain are described. Computational docking studies using an homology model of the M3 receptor readily explained the observed structure-activity relationship of the various compounds. Compound 14o was identified as a very potent, slowly reversible M3 antagonist with a very long in vivo duration of bronchoprotection.
Muscarinic acetylcholine receptor antagonists
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Page/Page column 21, (2008/06/13)
Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided.
ORGANIC COMPOUNDS
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Page/Page column 45, (2010/02/15)
The application relates to novel substituted piperidines of the general formula (I) in which R1, R2, R3, R4, W, X, Z, m and n are each as defined in detail in the description, to a process for their preparation and to the use of these compounds as medicines, in particular as renin inhibitors.
PHENETANOLAMINE DERIVATIVES
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Page/Page column 50, (2010/02/11)
Compounds of formula (I) and salts, solvates, and physiologically functional derivatives thereof, useful for the prophylaxis or treatment of a clinical condition for which a selective β2-adrenoreceptor agonist is indicated, for example asthma or chronic o
