50650-44-7

Upstream product

• 37742-98-6 4-Bromo-2,2-diphenylbutyric acid 
• 956-89-8 3,3-Diphenyl-dihydro-furan-2-one 

Downstream Products

• 336882-83-8 methyl 4-bromo-2,2-diphenylbutanoate 
• 53179-10-5 4-[4-chloro-3-(trifluoromethyl)phenyl]-4-hydroxy-N,N-dimethyl-α,α-diphenyl-1-piperidinebutanamide 
• 53179-11-6 loperamide 
• 786595-16-2 methyl 4-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2,2-diphenylbutanoate 
• 794591-41-6 4-[4-hydroxy-4-(3-trifluoromethyl-phenyl)-piperidin-1-yl]-2,2-diphenyl-butyric acid methyl ester 
• 794591-42-7 4-[4-(4-chloro-3-trifluoromethyl-phenyl)-4-hydroxy-piperidin-1-yl]-2,2-diphenyl-butyric acid methyl ester 
• 37743-19-4 diethyl(tetrahydro-3,3-diphenyl-2-furylidene)ammonium bromide 
• 37743-06-9 N-(tetrahydro-3,3-diphenyl-2-furylidene)methylamine hydrobromide 
• 37743-18-3 N-(dihydro-3,3-diphenyl-2(3H)-furanylidene)-N-methylmethanaminium bromide 
• 37743-08-1 4-chloro-N-methyl-2,2-diphenylbutanamid 
• 66164-07-6 Desmethylloperamide 
• 1055726-79-8 4-((S)-3-amino-pyrrolidin-1-yl)-N,N-diethyl-2,2-diphenyl-butyramide 
• 630425-65-9 3-[8-(3-dimethylcarbamoyl-3,3-diphenylpropyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]propionic acid ethyl ester 
• 630425-66-0 3-[8-(3-dimethylcarbamoyl-3,3-diphenylpropyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]propionic acid 

Relevant academic research and scientific papers

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 high-yield route to synthesize the P-glycoprotein radioligand [ 11C]N-desmethyl-loperamide and its parent radioligand [ 11C]loperamide

N-Desmethyl-loperamide and loperamide were synthesized from α,α-diphenyl-γ-butyrolactone and 4-(4-chlorophenyl)-4- hydroxypiperidine in five and four steps with 8% and 16% overall yield, respectively. The amide precursor was synthesized from 4-bromo-2,2- diphenylbutyronitrile and 4-(4-chlorophenyl)-4-hydroxypiperidine in 2 steps with 21-57% overall yield. [11C]N-Desmethyl-loperamide and [ 11C]loperamide were prepared from their corresponding amide precursor and N-desmethyl-loperamide with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20-30% and 10-15% radiochemical yields, respectively, based on [11C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.

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

4-OXADIAZOLYL-PIPERIDINE COMPOUNDS AND USE THEREOF

4-Oxadiazolyl-piperidine compounds of formula (I) and (II), their compositions and use for the treatment of pain and diarrhoea.

Design and synthesis of 4-phenyl piperidine compounds targeting the mu receptor

Small molecule mu agonists based on the 4-phenyl piperidine scaffold were designed and synthesized to further investigate the therapeutic potential of loperamide analogs. The resulting compounds show excellent agonistic activity towards the human mu receptor with interesting SAR trends within the series. Small molecule mu agonists based on the 4-phenyl piperidine scaffold were designed and synthesized to further investigate the therapeutic potential of loperamide analogs. The resulting compounds show excellent agonistic activity towards the human mu receptor with interesting SAR trends within the series.

1-PYRIDIN-4-YL-UREA DERIVATIVES

The invention relates to novel 1-pyridyn-4-yl urea derivatives and related compounds and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as neurohormonal antagonists.

2,2-DIPHENYLBUTANAMIDE DERIVATIVES AND MEDICINES CONTAINING THE SAME

2,2-Diphenylbutanamide derivatives represented by the following formula (1): [wherein A represents -(CH2)n- (n is 1 or 2) or a methine (CH) group; when A is -CH2-, B represents a methine group or a nitrogen atom, with A and B forming a single bond; when A is -(CH2)2-, B represents a nitrogen atom, with A and B forming a single bond; when A is a methine group, B represents a quaternary carbon atom, with A and B forming a double bond; each of R1 and R2, which are identical to or different from each other, represents a hydrogen atom, a lower alkyl group, or a cycloalkyl group, or R1 and R2 may form a heterocyclic ring together with the adjacent nitrogen atom; and Ar represents an optionally substituted phenyl group, bicyclic aromatic ring, monocyclic heterocyclic ring, bicyclic heterocyclic ring, or fluorene group]; or salts of the derivatives. The derivatives or salts thereof exhibit excellent μ-opioid agonist activity and analgesic activity against neuropathic pain, and are useful as medicines such as peripheral analgesic drugs and neuropathic pain relieving drugs.

Triazaspiro compounds, particularly 8-(3,3-diphenylpropyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane derivatives, with opioid receptor stimulating activity, useful for treating or preventing pain.

Triazaspiro Compounds, compositions comprising a Triazaspiro Compound, methods for treating or preventing pain in an animal comprising administering to an animal in need thereof an effective amount of a Triazaspiro Compound and methods for stimulating opioid-receptor function in a cell comprising contacting a cell capable of expressing an opioid receptor with an effective amount of a Triazaspiro Compound are disclosed.

4-hydroxy-4-phenylpiperidine derivatives and pharmaceuticals containing the same

Described is a 4-hydroxy-4-phenylpiperidine derivative represented by the following formula (1): [wherein, R1and R2are the same or different and each independently represents a hydrogen atom, a lower alkyl, or the like, R3represents a hydrogen atom or a group —(CR4R5)n—Y (in which, R4and R5each represents a hydrogen atom or a lower alkyl group, Y represents a group —COOR6, —CONR7R8, —OR9or —OCOR10(in which R6, R9and R10each independently represents a hydrogen atom, a lower alkyl group, or the like, R7and R8are the same or different and each independently represents a hydrogen atom, a lower alkyl group, or the like), and n stands for 1 to 6)], or salt thereof. The compound exhibits excellent peripheral analgesic action.