7254-21-9

Usage

Uses

Used in Pharmaceutical Industry:
1-Benzyl-4-(ALPHA-cyanobenzyl)-piperidine is used as a drug candidate for its potential therapeutic applications. Its unique structure allows it to target and modulate specific biological processes, making it a promising candidate for the development of new medications to treat various diseases and conditions.
Used in Medicinal Chemistry Research:
1-Benzyl-4-(ALPHA-cyanobenzyl)-piperidine is used as a subject of study in medicinal chemistry to better understand its properties and potential interactions with biological systems. This research can lead to the discovery of new drug targets and the development of more effective treatments.

InChI:InChI=1/C20H22N2/c21-15-20(18-9-5-2-6-10-18)19-11-13-22(14-12-19)16-17-7-3-1-4-8-17/h1-10,19-20H,11-14,16H2

Upstream product

• 6517-69-7 <1-benzylpiperidylidine-(4)>-phenylacetonitrile 
• 140-29-4 phenylacetonitrile 
• 3612-20-2 1-phenylmethyl-4-piperidone 

Downstream Products

• 1057333-14-8 C₂₄H₂₇N₃ 
• 2363165-42-6 rac-(1S,2R)-2-(2-methyl-4-(1-((1-(4-(pyridin-4-ylsulfonyl)phenyl)azetidin-3-yl)methyl)piperidin-4-yl)-1,2,3,4-tetrahydroisoquinolin-4-yl)cyclopentyl methylcarbamate 

Relevant academic research and scientific papers

Structure-Based Discovery of M-89 as a Highly Potent Inhibitor of the Menin-Mixed Lineage Leukemia (Menin-MLL) Protein-Protein Interaction

Inhibition of the menin-mixed lineage leukemia (MLL) protein-protein interaction is a promising new therapeutic strategy for the treatment of acute leukemia carrying MLL fusion (MLL leukemia). We describe herein our structure-based design, synthesis, and evaluation of a new class of small-molecule inhibitors of the menin-MLL interaction (hereafter called menin inhibitors). Our efforts have resulted in the discovery of highly potent menin inhibitors, as exemplified by compound 42 (M-89). M-89 binds to menin with a Kd value of 1.4 nM and effectively engages cellular menin protein at low nanomolar concentrations. M-89 inhibits cell growth in the MV4;11 and MOLM-13 leukemia cell lines carrying MLL fusion with IC50 values of 25 and 55 nM, respectively, and demonstrates >100-fold selectivity over the HL-60 leukemia cell line lacking MLL fusion. The determination of a co-crystal structure of M-89 in a complex with menin provides the structural basis for their high-affinity interaction. Further optimization of M-89 may lead to a new class of therapy for the treatment of MLL leukemia.

Design of the First-in-Class, Highly Potent Irreversible Inhibitor Targeting the Menin-MLL Protein–Protein Interaction

The structure-based design of M-525 as the first-in-class, highly potent, irreversible small-molecule inhibitor of the menin-MLL interaction is presented. M-525 targets cellular menin protein at sub-nanomolar concentrations and achieves low nanomolar potencies in cell growth inhibition and in the suppression of MLL-regulated gene expression in MLL leukemia cells. M-525 demonstrates high cellular specificity over non-MLL leukemia cells and is more than 30 times more potent than its corresponding reversible inhibitors. Mass spectrometric analysis and co-crystal structure of M-525 in complex with menin firmly establish its mode of action. A single administration of M-525 effectively suppresses MLL-regulated gene expression in tumor tissue. An efficient procedure was developed to synthesize M-525. This study demonstrates that irreversible inhibition of menin may be a promising therapeutic strategy for MLL leukemia.

PIPERIDINES AS MENIN INHIBITORS

The present disclosure provides compounds represented by Formula (I): (Formula(I)) and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R2, R3a, R3b, A, G, X, and Y are as defined as set forth in the specification. The present disclosure also provides compounds of Formula (I) for use to treat a condition or disorder responsive to menin inhibition such as cancer.