37136-99-5Relevant articles and documents
Chlorophenoxy aminoalkyl derivatives as histamine H3R ligands and antiseizure agents
Kuder, Kamil,?azewska, Dorota,Latacz, Gniewomir,Schwed, Johannes Stephan,Karcz, Tadeusz,Stark, Holger,Karolak-Wojciechowska, Janina,Kie?-Kononowicz, Katarzyna
, p. 53 - 72 (2016)
A series of twenty new chlorophenoxyalkylamine derivatives (9-28) was synthesized and evaluated on their binding properties at the human histamine H3 receptor (hH3R). The spacer alkyl chain contained five to seven carbon atoms. The h
Structure-activity relationships of imidazothiazinones and analogs as antagonists of the cannabinoid-activated orphan G protein-coupled receptor GPR18
Schoeder, Clara T.,Kaleta, Maria,Mahardhika, Andhika B.,Olejarz-Maciej, Agnieszka,?a?ewska, Dorota,Kie?-Kononowicz, Katarzyna,Müller, Christa E.
, p. 381 - 397 (2018/06/14)
GPR18 is a cannabinoid-activated orphan G protein-coupled receptor (GPCR) that is selectively expressed on immune cells. Despite its significant potential as a drug target for inflammatory diseases and cancer immunotherapy, only very few GPR18 ligands have been described to date. In the present study we investigated the structure-activity relationships (SARs) of (Z)-2-(3-(4-chlorobenzyloxy)benzylidene)-6,7-dihydro-2H-imidazo[2,1-b][1,3]thiazin-3(5H)-one (PSB-CB5, 5), the most potent GPR18 antagonist described to date. Analogs were synthesized that exhibit broad modifications of the heterocyclic core and/or variation of substituents at the benzylidene moiety. The compounds were investigated in β-arrestin recruitment assays as inhibitors of human GPR18 activation by tetrahydrocannabinol (THC). Selectivity was assessed versus the cannabinoid receptors (CB1 and CB2) and versus GPR55, another orphan GPCR that interacts with cannabinoids. Phenyloxyalkyloxy-substituted benzylidenethiazinones with long alkyl chains (optimal length: hexamethylene) efficiently blocked GPR18 with similarly high potency as lead structure 5. (Z)-2-(3-(6-(4-Chlorophenoxy)hexyloxy)benzylidene)-6,7-dihydro-2H-imidazo[2,1-b][1,3]thiazin-3(5H)-one (PSB-CB-27, 23) exhibited the best profile: it displayed an IC50 value of 650 nM at GPR18 and showed improved selectivity versus CB receptors as compared to lead structure 5. Importantly, in contrast to 5, which showed only partial inhibition (60%), 23 led to a complete blockade of THC-induced GPR18 activation and is thus a superior tool for target validation. In addition, several compounds, e.g. 18 and 22, were identified as dual GPR18/GPR55 antagonists with similar potency at both targets, and selectivity versus CB receptors.
Synthesis and biological evaluation of vinyl ether-containing azole derivatives as inhibitors of Trichophyton rubrum
Wang, Lulu,Yang, Wenge,Wang, Kai,Zhu, Jing,Shen, Fei,Hu, Yonghong
scheme or table, p. 4887 - 4890 (2012/08/07)
In an attempt to search for many target compounds with excellent activities, a series of vinyl ether-containing azole derivatives were designed, synthesized, and evaluated as antifungal agents. Results of preliminary antifungal tests against Trichophyton rubrum in vitro indicated that most of the synthesized compounds showed excellent activities. In comparison with fluconazole, itraconazole, voriconazole, omoconazole and amphotericin B, several compounds (such as 7d, 7g and 7h) exhibited more potent inhibitory activities, suggesting that they were promising leads for the development of novel antifungal agents.
