151519-23-2Relevant academic research and scientific papers
Discovery of Adamantyl Heterocyclic Ketones as Potent 11β-Hydroxysteroid Dehydrogenase Type1 Inhibitors
Su, Xiangdong,Vicker, Nigel,Thomas, Mark P.,Pradaux-Caggiano, Fabienne,Halem, Heather,Culler, Michael D.,Potter, Barry V.L.
, p. 1439 - 1451 (2011)
11β-Hydroxysteroid dehydrogenase type1 (11β-HSD1) plays a key role in converting intracellular cortisone to physiologically active cortisol, which is implicated in the development of several phenotypes of metabolic syndrome. Inhibition of 11β-HSD1 activity with selective inhibitors has beneficial effects on various conditions, including diabetes, dyslipidemia and obesity, and therefore constitutes a promising strategy to discover novel therapies for metabolic and cardiovascular diseases. A series of novel adamantyl heterocyclic ketones provides potent and selective inhibitors of human 11β-HSD1. Lead compounds display low nanomolar inhibition against human and mouse 11β-HSD1 and are selective with no activity against 11β-HSD2 and 17β-HSD1. Selected potent 11β-HSD1 inhibitors show moderate metabolic stability upon incubation with human liver microsomes and weak inhibition of human CYP450 enzymes.
Identifying new lead structures to enhance tolerance towards drought stress via high-throughput screening giving crops a quantum of solace
Frackenpohl, Jens,Schneider, Linn,Decker, Luka J.B.,Dittgen, Jan,Fenkl, Franz,Fischer, Christian,Franke, Jana,Freigang, Joerg,Getachew, Rahel,Gonzalez Fernandez-Nino, Susana M.,Helmke, Hendrik,Hills, Martin J.,Hohmann, Sabine,Kleemann, Jochen,Kurowski, Karoline,Lange, Gudrun,Luemmen, Peter,Meyering, Nicole,Poree, Fabien,Schmutzler, Dirk,Wrede, Sebastian
, (2019/11/13)
Novel synthetic lead structures interacting with RCAR/(PYR/PYL) receptor proteins were identified based on the results of a high-throughput screening campaign of a large compound library followed by focused SAR studies of the three most promising hit clusters. Whilst indolinylmethyl sulfonamides 8y,z and phenylsulfonyl ethylenediamines 9y,z showed strong affinities for RCAR/ (PYR/PYL) receptor proteins in wheat, thiotriazolyl acetamides 7f,s exhibited promising efficacy against drought stress in vivo (wheat, corn and canola) combined with confirmed target interaction in wheat and arabidopsis thaliana. Remarkably, binding affinities of several representatives of 8 and 9 were on the same level or even better than the essential plant hormone abscisic acid (ABA).
