63214-57-3

Usage

InChI:InChI=1/C10H18N2O2.ClH/c13-10(9-1-3-11-4-2-9)12-5-7-14-8-6-12;/h9,11H,1-8H2;1H

Upstream product

• 757949-38-5 4-(piperidine-1-carbonyl)-piperidine-1-carboxylic acid tert-butyl ester 
• 84358-13-4 N-[(tert-butoxy)carbonyl]piperidine-4-carboxylic acid 

Downstream Products

• 957054-84-1 4-({1-[1-(diphenylmethyl)azetidin-3-yl]piperidin-4-yl}carbonyl)morpholine 
• 1226860-78-1 C₂₆H₃₉N₃O₄ 
• 1415678-49-7 C₂₅H₃₁N₅O₂ 
• 1443125-02-7 4-(morpholine-4-carbonyl)-N-(3-((6-oxo-3-(o-tolylamino)pyridazin-1(6H)-yl)methyl) phenyl)piperidine-1-carboxamide 
• 666850-79-9 2-[1,1-dimethyl-2-oxo-2-(7-azabicyclo[2.2.1]heptan-7-yl)ethyl]-4-[2-(4-{morpholinocarbonyl}piperidin-1-yl)ethyl]-5-(3,5-dimethylphenyl)-6H-thieno[2,3-b]pyrrole 
• 35091-01-1 4-[1-(3,4-dimethoxy-phenethyl)-piperidine-4-carbonyl]-morpholine 

Relevant academic research and scientific papers

Covalent docking modelling-based discovery of tripeptidyl epoxyketone proteasome inhibitors composed of aliphatic-heterocycles

The potential of specific proteasome inhibitors to act as anti-cancer agents has attracted intensive investigations. The proteasome can be covalently inhibited by epoxyketone derivatives via a two-step reaction. Several computational approaches have been developed to mimic the covalent binding event. Compound 1 composed of a six-membered heterocyclic ring was designed by using covalent docking. With a possible different binding mode from the clinical compound Carfilzomib, it occupied the S5 pocket of 20S proteasome and showed favorable inhibitory activity. Subsequently optimization and evaluation were taken place. Among these compounds, 11h demonstrated extraordinary in vitro inhibitory activity and selectivity, and good in vivo proteasome inhibitory activity, a favorable pharmacokinetic profile and xenograft tumor inhibition. The possible binding pattern of compound 11h against proteasome was further fully explored via calculations, providing a theoretical basis for finding potent proteasome inhibitors.

COMPOUNDS AND USES THEREOF

The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.

Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen

WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. We report the discovery and optimization of a 3,4,5-trisubstituted pyridine 9 using a high-throughput cell-based reporter assay of WNT pathway activity. We demonstrate a twisted conformation about the pyridine-piperidine bond of 9 by small-molecule X-ray crystallography. Medicinal chemistry optimization to maintain this twisted conformation, cognisant of physicochemical properties likely to maintain good cell permeability, led to 74 (CCT251545), a potent small-molecule inhibitor of WNT signaling with good oral pharmacokinetics. We demonstrate inhibition of WNT pathway activity in a solid human tumor xenograft model with evidence for tumor growth inhibition following oral dosing. This work provides a successful example of hypothesis-driven medicinal chemistry optimization from a singleton hit against a cell-based pathway assay without knowledge of the biochemical target.