3412-68-8Relevant 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.
NOVEL COMPOSITIONS COMPRISING STRUCTURAL ISOMERS OF 1,4-CYCLOHEXANEDIMETHANOL DIBENZOATE AND POLYMER COMPOSITIONS CONTAINING SAME
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Paragraph 0034, (2014/07/23)
Novel solid benzoate ester compositions are mixtures comprising the trans- and cis-structural isomers of 1,4-cyclohexanedimethanol dibenzoate wherein the trans isomer constitutes from 1 to 66 or from 72 to 99 weight percent of the mixture. The properties imparted to a variety of polymer compositions, including hot melt adhesives, cannot be achieved using the commercially available mixture of these isomers.
