We designed and synthesized a new biphenyl amide-tryptamine hybrid molecule utilizing a pharmacophore-based approach as a 5-HT antagonist. The hybrid compound was evaluated for its affinity to a panel of seven 5-HT receptors， demonstrating high selectivity for the 5-HT receptor. Functional assays revealed potent antagonism of 5-HT by with an IC value of 14.1 nM. Moreover， compound possessed a desirable 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 antagonists.
We designed and synthesized a new biphenyl amide-tryptamine hybrid molecule utilizing a pharmacophore-based approach as a 5-HT antagonist. The hybrid compound was evaluated for its affinity to a panel of seven 5-HT receptors， demonstrating high selectivity for the 5-HT receptor. Functional assays revealed potent antagonism of 5-HT by with an IC value of 14.1 nM. Moreover， compound possessed a desirable 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 antagonists.
