80100-22-7Relevant 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
supporting information, 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.
2-halo-pyridines
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, (2008/06/13)
2-Halo-pyridines of the general formula I STR1 wherein X is Cl or Br; A is =0 or STR2 Ar is phenyl or substituted phenyl of the general formula STR3 in which n is 0, 1, 2 or 3; R is alkyl C1-4, alkoxy C1-4, phenoxy, alkylthio C1-4, halogen especially F and Cl, OH or C6 H5 ; and their salts, addition compounds and precursors (prodrugs). Furthermore the invention is directed to the production of these compounds and pharmaceuticals containing them.
