- Discovery of thienopyridines as Src-family selective Lck inhibitors
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We describe the identification, SAR, and in vivo pharmacology of a new series of Src-family selective Lck inhibitors. These thienopyridines were designed based on a desire to access the unique residues in the extended hinge region of Lck.
- Abbott, Lily,Betschmann, Patrick,Burchat, Andrew,Calderwood, David J.,Davis, Heather,Hrnciar, Peter,Hirst, Gavin C.,Li, Biqin,Morytko, Michael,Mullen, Kelly,Yang, Bryant
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Read Online
- Synthesis of Enantiomerically Pure Ring-Substituted l -Pyridylalanines by Biocatalytic Hydroamination
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Current routes to nitrogen-containing heteroarylalanines involve complex multistep synthesis and are often reliant on protection/deprotection steps and wasteful chromatographic purifications. In order to complement existing methodologies, a convenient telescopic strategy was developed for the synthesis of l-pyridylalanine analogues (12 examples) and other l-heteroarylalanines (5 examples) starting from the corresponding aldehydes. A phenylalanine ammonia lyase (PAL) from Anabaena variabilis was used as the biocatalyst to give conversions ranging between 88 and 95%, isolated yields of 32-60%, and perfect enantiopurity (>99% ee) by employing an additional deracemization cascade where necessary.
- Ahmed, Syed T.,Parmeggiani, Fabio,Weise, Nicholas J.,Flitsch, Sabine L.,Turner, Nicholas J.
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supporting information
p. 5468 - 5471
(2016/11/17)
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- NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A
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The present invention relates to novel compounds of the formula I which are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders
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Paragraph 1151
(2013/05/21)
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- Structure-activity relationships of trans-substituted-propenoic acid derivatives on the nicotinic acid receptor HCA2 (GPR109A)
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Nicotinic acid (niacin) has been used for decades as an antidyslipidemic drug in man. Its main target is the hydroxy-carboxylic acid receptor HCA2 (GPR109A), a G protein-coupled receptor. Other acids and esters such as methyl fumarate also interact with the receptor, which constituted the basis for the current study. We synthesized a novel series of substituted propenoic acids, such as fumaric acid esters, fumaric acid amides and cinnamic acid derivatives, and determined their affinities for the HCA2 receptor. We observed a rather restricted binding pocket on the receptor with trans-cinnamic acid being the largest planar ligand in our series with appreciable affinity for the receptor. Molecular modeling and analysis of the structure-activity relationships in the series suggest a planar trans-propenoic acid pharmacophore with a maximum length of 8 ? and out-of-plane orientation of the larger substituents.
- Van Veldhoven,Blad,Artsen,Klopman,Wolfram,Abdelkadir,Lane,Brussee,Ijzerman
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supporting information; experimental part
p. 2736 - 2739
(2011/06/20)
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- Improved synthesis of 3-substituted-4-amino-[3,2-c]-thienopyridines
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(Chemical Equation Presented) Two syntheses of 3-substituted-4-amino-[3,2- c]thienopyridines have been developed to replace the standard literature route to these compounds, which uses unattractive conditions involving azide and high temperatures. The fir
- Engstrom, Kenneth M.,Baize, Amanda L.,Franczyk, Thaddeus S.,Kallemeyn, Jeffrey M.,Mulhern, Mathew M.,Rickert, Robert C.,Wagaw, Seble
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experimental part
p. 3849 - 3855
(2009/09/26)
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- Heteroarylacrylamides and their use as pharmaceuticals for the stimulation of the expression of endothelial NO synthase
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The present invention relates to heteroarylacrylamides of the formula I, in which Het, X, Ra, Rb, R1, R2 and R3 have the meanings indicated in the claims, which modulate the transcription of endotheli
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Page/Page column 38
(2008/12/06)
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- Design and effective synthesis of novel templates, 3,7-diphenyl-4-amino-thieno and furo-[3,2-c]pyridines as protein kinase inhibitors and in vitro evaluation targeting angiogenetic kinases
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A novel class of 3,7-diphenyl-4-amino-thieno and furo[3,2-c]pyridine has been designed based on pharmacophore models of ATP competitive kinase inhibitors. Versatile synthetic methods via double Suzuki coupling to explore SAR have been established and potent inhibitors against angiogenetic targets, VEGFR2, Tie-2, and EphB4, have been successfully discovered.
- Miyazaki, Yasushi,Nakano, Masato,Sato, Hideyuki,Truesdale, Anne T.,Stuart, J. Darren,Nartey, Eldridge N.,Hightower, Kendra E.,Kane-Carson, Laurie
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p. 250 - 254
(2007/10/03)
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- Compounds
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Thienopyridine compounds which are potassium channel inhibitors are described. Pharmaceutical compositions comprising the compounds and their use in the treatment or prevention of cancer, arrhythmias, autoimmune diseases and inflammatory diseases, including gastric cancer, atrial fibrillation, type-2 diabetes mellitus, rheumatoid arthritis, type-1 diabetes, inflammatory bowel disorder and demyelinating disorders such as multiple sclerosis are also disclosed.
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Page/Page column 8
(2010/11/27)
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- NOVEL CHEMICAL COMPOUNDS
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This invention relates to newly identified compounds for treating and preventing tumors ans cancers, and methods for treating proliferative diseases associated with the imbalance or inappropriate activity of tyrosine kinases implicated in proliferative diseases.
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- Nitrogen containing heterocyclic compounds
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Compounds of the formula (III): STR1 or salts or acyl derivatives thereof, for use as antifungal and antiprotozoal agents are disclosed. Compositions containing the compounds are also disclosed as are method for the preparation of the compounds and interm
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