1609938-68-2Relevant academic research and scientific papers
Direct NMR Probing of Hydration Shells of Protein Ligand Interfaces and Its Application to Drug Design
Geist, Leonhard,Mayer, Moriz,Cockcroft, Xiao-Ling,Wolkerstorfer, Bernhard,Kessler, Dirk,Engelhardt, Harald,McConnell, Darryl B.,Konrat, Robert
, p. 8708 - 8715 (2017/11/15)
Fragment-based drug design exploits initial screening of low molecular weight compounds and their concomitant affinity improvement. The multitude of possible chemical modifications highlights the necessity to obtain structural information about the binding mode of a fragment. Herein we describe a novel NMR methodology (LOGSY titration) that allows the determination of binding modes of low affinity binders in the protein-ligand interface and reveals suitable ligand positions for the addition of functional groups that either address or substitute protein-bound water, information of utmost importance for drug design. The particular benefit of the methodology and in contrast to conventional ligand-based methods is the independence of the molecular weight of the protein under study. The validity of the novel approach is demonstrated on two ligands interacting with bromodomain 1 of bromodomain containing protein 4, a prominent cancer target in pharmaceutical industry.
TRIAZOLOPYRIDAZINE
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Paragraph 0311-0314, (2014/05/20)
Disclosed are compounds of general formula (I) wherein the groups R1 to R3 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.
TRIAZOLOPYRIDAZINE
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Page/Page column 52, (2014/06/11)
The present invention encompasses compounds of general formula (I), wherein the groups R1 to R3 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.
TRIAZOLOPYRAZINE
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Paragraph 0275 - 0278, (2014/05/25)
Disclosed are compounds of the formula (I) wherein the groups R1 to R3 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.
