274672-75-2Relevant academic research and scientific papers
Guanidine Derivatives: How Simple Structural Modification of Histamine H3R Antagonists Has Led to the Discovery of Potent Muscarinic M2R/M4R Antagonists
Staszewski, Marek,Nelic, Dominik,Jończyk, Jakub,Dubiel, Mariam,Frank, Annika,Stark, Holger,Bajda, Marek,Jakubik, Jan,Walczyński, Krzysztof
, p. 2503 - 2519 (2021/06/30)
This article describes the discovery of novel potent muscarinic receptor antagonists identified during a search for more active histamine H3 receptor (H3R) ligands. The idea was to replace the flexible seven methylene linker with a semirigid 1,4-cyclohexylene or p-phenylene substituted group of the previously described histamine H3R antagonists ADS1017 and ADS1020. These simple structural modifications of the histamine H3R antagonist led to the emergence of additional pharmacological effects, some of which unexpectedly showed strong antagonist potency at muscarinic receptors. This paper reports the routes of synthesis and pharmacological characterization of guanidine derivatives, a novel chemotype of muscarinic receptor antagonists binding to the human muscarinic M2 and M4 receptors (hM2R and hM4R, respectively) in nanomolar concentration ranges. The affinities of the newly synthesized ADS10227 (1-{4-{4-{[4-(phenoxymethyl)cyclohexyl]methyl}piperazin-1-yl}but-1-yl}-1-(benzyl)guanidine) at hM2R and hM4R were 2.8 nM and 5.1 nM, respectively.
Discovery libraries targeting the major enzyme classes: The serine hydrolases
Otrubova, Katerina,Srinivasan, Venkat,Boger, Dale L.
supporting information, p. 3807 - 3813 (2014/09/16)
Two libraries of modestly reactive ureas containing either electron-deficient acyl anilines or acyl pyrazoles were prepared and are reported as screening libraries for candidate serine hydrolase inhibitors. Within each library is a small but powerful subs
Triazolo and derivatives as chemokine inhibitors
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, (2008/06/13)
Novel triazolo derivatives represented by the following formula and pharmaceutically acceptable salts thereof, as well as chemokine inhibitors containing the same as an effective component. These are useful as therapeutic agents for allergic diseases such
