Products Cited in Publications Worldwide Design and Synthesis of D3R Bitopic Ligands with Flexible Secondary Binding Fragments: Radioligand Binding and Computational Chemistry Studies

Design and Synthesis of D3R Bitopic Ligands with Flexible Secondary Binding Fragments: Radioligand Binding and Computational Chemistry Studies

Tian, Gui-Long; Hsieh, Chia-Ju; Taylor, Michelle; Lee, Ji Youn; Luedtke, Robert R.; Mach, Robert H.

DOI: PMID:

Abstract

A series of bitopic ligands based on Fallypride with a flexible secondary binding fragment (SBF) were prepared with the goal of preparing a D3R-selective compound The effect of the flexible linker ((R,S)-trans-2a-d), SBFs ((R,S)-trans-2h-j), and the chirality of orthosteric binding fragments (OBFs) ((S,R)-trans-d, (S,R)-trans-i, (S,S)-trans-d, (S,S)-trans-i, (R,R)-trans-d, and (R,R)-trans-i) were evaluated in in vitro binding assays. Computational chem. studies revealed that the interaction of the fragment binding to the SBF increased the distance between the pyrrolidine nitrogen and ASP1103.32 of the D3R, thereby reducing the D3R affinity to a suboptimal level.

Keywords

dopamine 2 receptor ; dopamine 3 receptor ; flexible linker ; bitopic ligands ; molecular dynamic simulation

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CDI

A691302530-62-198%

CDI

18.0/100g

Detail