186589-83-3Relevant academic research and scientific papers
First Structure-Activity Relationship of 17β-Hydroxysteroid Dehydrogenase Type 14 Nonsteroidal Inhibitors and Crystal Structures in Complex with the Enzyme
Braun, Florian,Bertoletti, Nicole,M?ller, Gabriele,Adamski, Jerzy,Steinmetzer, Torsten,Salah, Mohamed,Abdelsamie, Ahmed S.,Van Koppen, Chris J.,Heine, Andreas,Klebe, Gerhard,Marchais-Oberwinkler, Sandrine
, p. 10719 - 10737 (2016/12/16)
17β-HSD14 belongs to the SDR family and oxidizes the hydroxyl group at position 17 of estradiol and 5-androstenediol using NAD+ as cofactor. The goal of this study was to identify and optimize 17β-HSD14 nonsteroidal inhibitors as well as to disclose their structure-activity relationship. In a first screen, a library of 17β-HSD1 and 17β-HSD2 inhibitors, selected with respect to scaffold diversity, was tested for 17β-HSD14 inhibition. The most interesting hit was taken as starting point for chemical modification applying a ligand-based approach. The designed compounds were synthesized and tested for 17β-HSD14 inhibitory activity. The two best inhibitors identified in this study have a very high affinity to the enzyme with a Ki equal to 7 nM. The strong affinity of these inhibitors to the enzyme active site could be explained by crystallographic structure analysis, which highlighted the role of an extended H-bonding network in the stabilization process. The selectivity of the most potent compounds with respect to 17β-HSD1 and 17β-HSD2 is also addressed.
4-AMINO-6-(HETEROCYCLIC)PICOLINATES AND 6-AMINO-2-(HETEROCYCLIC)PYRIMIDINE-4-CARBOXYLATES AND THEIR USE AS HERBICIDES
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Paragraph 0250; 0251, (2014/09/29)
Novel 4-amino-6-(heterocyclic)picolinic acids and their derivatives and 6-amino-2-(heterocyclic)pyrimidine-4-carboxylates and their derivatives are useful to control undesirable vegetation.
