4537-73-9Relevant articles and documents
Synthesis and Characterization of the Novel Rodent-Active and CNS-Penetrant P2X7 Receptor Antagonist Lu AF27139
Hopper, Allen T.,Juhl, Martin,Hornberg, Jorrit,Badolo, Lassina,Kilburn, John Paul,Thougaard, Annemette,Smagin, Gennady,Song, Dekun,Calice, Londye,Menon, Veena,Dale, Elena,Zhang, Hong,Cajina, Manuel,Nattini, Megan E.,Gandhi, Adarsh,Grenon, Michel,Jones, Ken,Khayrullina, Tanzilya,Chandrasena, Gamini,Thomsen, Christian,Zorn, Stevin H.,Brodbeck, Robb,Poda, Suresh Babu,Staal, Roland,M?ller, Thomas
supporting information, p. 4891 - 4902 (2021/05/07)
There remains an insufficient number of P2X7 receptor antagonists with adequate rodent potency, CNS permeability, and pharmacokinetic properties from which to evaluate CNS disease hypotheses preclinically. Herein, we describe the molecular pharmacology, s
Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives
Sahin, Zafer,Ertas, Merve,Berk, Bark?n,Biltekin, Sevde Nur,Yurttas, Leyla,Demirayak, Seref
, p. 1986 - 1995 (2018/03/12)
Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects. Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition. In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC50:0.42 nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site.
From liquid to solid-state fluorescence: Tricyclic lactones based on 4-hydroxy-1,3-thiazoles
Calderón Ortiz, Lorena K.,Würfel, Hendryk,T?uscher, Eric,Wei, Dieter,Birckner, Eckhard,G?rls, Helmar,Beckert, Rainer
, p. 126 - 134 (2014/01/06)
This work describes the synthesis of a series of tricyclic lactones based on 4-hydroxy-1,3-thiazoles prepared by the classic Hantzsch synthesis. The tricyclic lactones are more rigid than the parent 4-hydroxythiazoles and are featured not only by fluorescence in solution, but also in the solid state. An extension of the chromophoric system was successfully realized by integration of the benzothiazole substructure, thus resulting in bathochromic shifts of absorption and also fluorescence. The new synthesized lactones additionally show interesting properties in solution, whereby the initial blue fluorescence changes dramatically with a variation of the pH value. Georg Thieme Verlag Stuttgart · New York.
