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• W2950280690 endingPage "103071" @default.
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• W2950280690 abstract "A novel series of 4-pyridylpiperazine derivatives with varying alkyl linker length and eastern part substituents proved to be potent histamine H3 receptor (hH3R) ligands in the nanomolar concentration range. While paying attention to their alkyl linker length, derivatives with a six methylene linker tend to be more potent than their five methylene homologues. Moreover, in the case of both phenoxyacetyl- and phenoxypropionyl- derivatives, an eight methylene linkers possess lower activity than their seven methylene homologues. However, in global analysis of collected data on the influence of alkyl linker length, a three methylene homologues appeared to be of highest hH3R affinity among all described 4-pyridylpiperazine derivatives from our group up to date. In the case of biphenyl and benzophenone derivatives, compounds with para- substituted second aromatic ring were of higher affinity than their meta analogues. Interestingly, benzophenone derivative 18 showed the highest affinity among all tested compounds (hH3R Ki = 3.12 nM). The likely protein-ligand interactions, responsible for their high affinity were demonstrated using molecular modeling techniques. Furthermore, selectivity, intrinsic activity at H3R, as well as drug-like properties of selected ligands were evaluated using in vitro methods." @default.
• W2950280690 created "2019-06-27" @default.
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• W2950280690 date "2019-10-01" @default.
• W2950280690 modified "2023-09-23" @default.
• W2950280690 title "Structural modifications and in vitro pharmacological evaluation of 4-pyridyl-piperazine derivatives as an active and selective histamine H3 receptor ligands" @default.
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• W2950280690 doi "https://doi.org/10.1016/j.bioorg.2019.103071" @default.
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