1426322-87-3

Upstream product

• 30005-58-4 4-(4-chlorophenyl)-1,2,3,6-tetrahydropyridine 
• 39186-58-8 4-bromo-2,2-diphenylbutyronitrile 
• 39512-49-7 4-(4-chlorophenyl)-4-hydroxypiperidine 
• 51304-61-1 4-(4-chlorophenyl)-1,2,3,6-tetrahydropyridine hydrochloride 
• 138647-50-4 4-(4-Chloro-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 138647-49-1 4-Trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 

Relevant academic research and scientific papers

1,4-disubstituted -1, 2, 3, 6- tetrahydropyridine compound, as well as preparation method, pharmaceutical composition and application thereof

The invention provides 1,4-disubstituted-1,2,3,6-tetrahydropyridine compounds which are shown in a general formula I, and a preparation method, pharmaceutical compositions and an application thereof.In particular, the compounds provided by the invention a

Identification of novel small-molecule inhibitors targeting menin-MLL interaction, repurposing the antidiarrheal loperamide

Leukemia with a mixed lineage leukemia (MLL) rearrangement, which harbors a variety of MLL fusion proteins, has a poor prognosis despite the latest improved treatment options. Menin has been reported to be a required cofactor for the leukemogenic activity of MLL fusion proteins. Thus, the disruption of the protein-protein interactions between menin and MLL represents a very promising strategy for curing MLL leukemia. Making use of menin-MLL inhibitors with a shape-based scaffold hopping approach, we have discovered that the antidiarrheal loperamide displays previously unreported mild inhibition for the menin-MLL interaction (IC50 = 69 ± 3 μM). In an effort to repurpose this drug, a series of chemical modification analyses was performed, and three of the loperamide-based analogues, DC-YM21, DC-YM25 and DC-YM26 displayed better activities with IC50 values of 0.83 ± 0.13 μM, 0.69 ± 0.07 μM and 0.66 ± 0.05 μM, respectively. Further treatment with DC-YM21 demonstrated potent and selective blockage of proliferation and induction of both cell cycle arrest and differentiation of leukemia cells harboring MLL translocations, which confirmed the specific mechanism of action. In conclusion, molecules of a novel scaffold targeting menin-MLL interactions were reported and they may serve as new potential therapeutic agents for MLL leukemia.

A facile synthesis for novel loperamide analogs as potential μ opioid receptor agonists

A facile synthesis for novel loperamide analogs as potential μ opioid receptors is described. The synthetic procedure for compound 5, which contains two 4-phenyl piperidine scaffolds, was optimized, and this compound was synthesized in excellent yield. We