84859-47-2Relevant articles and documents
THIOPHENE DERIVATIVES FOR THE TREATMENT OF DISORDERS CAUSED BY IGE
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Page/Page column 183, (2020/01/11)
Thiophene derivatives of formula (I) and a pharmaceutically acceptable salt thereof are provided. These compounds have utility for the treatment or prevention of disorders caused by IgE, such as allergy, type 1 hypersensitivity or familiar sinus inflammation.
A comparative study of fragment screening methods on the p38α kinase: New methods, new insights
Pollack, Scott J.,Beyer, Kim S.,Lock, Christopher,Mueller, Ilka,Sheppard, David,Lipkin, Mike,Hardick, David,Blurton, Peter,Leonard, Philip M.,Hubbard, Paul A.,Todd, Daniel,Richardson, Christine M.,Ahrens, Thomas,Baader, Manuel,Hafenbradl, Doris O.,Hilyard, Kate,Buerli, Roland W.
scheme or table, p. 677 - 687 (2012/07/16)
The stress-activated kinase p38α was used to evaluate a fragment-based drug discovery approach using the BioFocus fragment library. Compounds were screened by surface plasmon resonance (SPR) on a Biacore T100 against p38α and two selectivity targets. A sub-set of our library was the focus of detailed follow-up analyses that included hit confirmation, affinity determination on 24 confirmed, selective hits and competition assays of these hits with respect to a known ATP binding site inhibitor. In addition, functional activity against p38α was assessed in a biochemical assay using a mobility shift platform (LC3000, Caliper LifeSciences). A selection of fragments was also evaluated using fluorescence lifetime (FLEXYTE) and microscale thermophoresis (Nanotemper) technologies. A good correlation between the data for the different assays was found. Crystal structures were solved for four of the small molecules complexed to p38α. Interestingly, as determined both by X-ray analysis and SPR competition experiments, three of the complexes involved the fragment at the ATP binding site, while the fourth compound bound in a distal site that may offer potential as a novel drug target site. A first round of optimization around the remotely bound fragment has led to the identification of a series of triazole-containing compounds. This approach could form the basis for developing novel and active p38α inhibitors. More broadly, it illustrates the power of combining a range of biophysical and biochemical techniques to the discovery of fragments that facilitate the development of novel modulators of kinase and other drug targets.
Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3
Malerich, Jeremiah P.,Lam, Jennifer S.,Hart, Barry,Fine, Richard M.,Klebansky, Boris,Tanga, Mary J.,D'Andrea, Annalisa
scheme or table, p. 7454 - 7457 (2011/01/12)
Tyrosine kinase 2 (TYK2) is required for signaling of interleukin-23 (IL-23), which plays a key role in rheumatoid arthritis. Presented is the design and synthesis of 1,2,4-triazoles, and the evaluation of their inhibitory activity against the Janus associated kinases TYK2 and JAKs 1-3.
INHIBITORS OF DIACYLGLYCEROL O-ACYLTRANSFERASE TYPE 1 ENZYME
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Page/Page column 68, (2010/11/29)
The present invention relates to compounds of formula (I) wherein R1, R3, X, Q, Z, A, D, m, and n are defined herein. Pharmaceutical compositions and methods for treating DGAT-1 related diseases or conditions are also disclosed.
Diphenyl Cyanocarbonimidate. A Versatile Synthon for the Construction of Heterocyclic Systems
Webb, R. Lee,Labaw, Clifford S.
, p. 1205 - 1206 (2007/10/02)
A simple high yield synthesis of diphenyl cyanocarbonimidate is reported.This synthon may be used to prepare functionalized benzimidazoles, benzoxazoles and triazoles in good yield under mild conditions.
