biostudies-literatureUnknown9(6)Gabr MTWe designed and synthesized a new biphenyl amide-tryptamine hybrid molecule <b>7</b> utilizing a pharmacophore-based approach as a 5-HT_2B antagonist. The hybrid compound <b>7</b> was evaluated for its affinity to a panel of seven 5-HT receptors, demonstrating high selectivity for the 5-HT_2B receptor. Functional assays revealed potent antagonism of 5-HT_2B by <b>7</b> with an IC₅₀ value of 14.1 nM. Moreover, compound <b>7</b> possessed a desirable <i>in vitro</i> pharmacokinetic profile and maintained its antagonistic potency in the presence of physiological concentrations of serum proteins. The design approach implemented in this investigation would facilitate the development of a second generation of highly selective and potent 5-HT_2B antagonists.MedChemComm1069-1075https://www.ebi.ac.uk/biostudies/studies/S-EPMC6072314biostudies-literaturePharmacophore-based tailoring of biphenyl amide derivatives as selective 5-hydroxytryptamine 2B receptor antagonists.PMC6072314Gabr MTAbdel-Raziq MSfalsePharmacophore-based tailoring of biphenyl amide derivatives as selective 5-hydroxytryptamine 2B receptor antagonists.We designed and synthesized a new biphenyl amide-tryptamine hybrid molecule <b>7</b> utilizing a pharmacophore-based approach as a 5-HT_2B antagonist. The hybrid compound <b>7</b> was evaluated for its affinity to a panel of seven 5-HT receptors, demonstrating high selectivity for the 5-HT_2B receptor. Functional assays revealed potent antagonism of 5-HT_2B by <b>7</b> with an IC₅₀ value of 14.1 nM. Moreover, compound <b>7</b> possessed a desirable <i>in vitro</i> pharmacokinetic profile and maintained its antagonistic potency in the presence of physiological concentrations of serum proteins. The design approach implemented in this investigation would facilitate the development of a second generation of highly selective and potent 5-HT_2B antagonists.2018-01-01T00:00:00Z2018 Jun2024-11-21T10:10:02.891Z2019-06-06T23:21:33ZS-EPMC60723143010899610.1039/c8md00204e