Structure-Based Design of High-Affinity Macrocyclic FKBP51 Inhibitors was written by Bauder, Michael;Meyners, Christian;Purder, Patrick L.;Merz, Stephanie;Sugiarto, Wisely Oki;Voll, Andreas M.;Heymann, Tim;Hausch, Felix. And the article was included in Journal of Medicinal Chemistry in 2021.COA of Formula: C21H21NO4 The following contents are mentioned in the article:
The FK506-binding protein 51 (FKBP51) emerged as a key player in several diseases like stress-related disorders, chronic pain, and obesity. Linear analogs of FK506 called SAFit were shown to be highly selective for FKBP51 over its closest homolog FKBP52, allowing the proof-of-concept studies in animal models. Here, we designed and synthesized the first macrocyclic FKBP51-selective ligands to stabilize the active conformation. All macrocycles retained full FKBP51 affinity and selectivity over FKBP52 and the incorporation of polar functionalities further enhanced affinity. Six high-resolution crystal structures of macrocyclic inhibitors in complex with FKBP51 confirmed the desired selectivity-enabling binding mode. Our results show that macrocyclization is a viable strategy to target the shallow FKBP51 binding site selectively. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5COA of Formula: C21H21NO4).
(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.COA of Formula: C21H21NO4
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem