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. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.COA of Formula: C21H21NO4
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem