66164-07-6

Usage

Uses

Used in Pharmaceutical Applications:
DESMETHYL LOPERAMIDE is used as an active metabolite for its peripheral μ opioid receptor activation, which contributes to the overall efficacy of Loperamide in treating diarrhea and other gastrointestinal disorders. Its restricted passage through the blood-brain barrier minimizes the risk of central nervous system side effects, such as addiction and respiratory depression.
Used in Research and Analysis:
DESMETHYL LOPERAMIDE serves as a subject of study in various research fields, including pharmacology, drug metabolism, and drug transport. Its analysis in biological samples is essential for understanding the pharmacokinetics, pharmacodynamics, and potential drug-drug interactions involving Loperamide and its metabolites.
Used in Drug Development:
DESMETHYL LOPERAMIDE may be utilized in the development of new drugs with improved efficacy and safety profiles. Understanding its properties and interactions with biological systems can guide the design of novel therapeutic agents targeting the μ opioid receptors for various medical conditions.

InChI:InChI=1/C28H31ClN2O2/c1-30-26(32)28(23-8-4-2-5-9-23,24-10-6-3-7-11-24)18-21-31-19-16-27(33,17-20-31)22-12-14-25(29)15-13-22/h2-15,33H,16-21H2,1H3,(H,30,32)

Upstream product

• 66164-06-5 4-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2,2-diphenylbutanamide 
• 74-88-4 methyl iodide 
• 956-89-8 3,3-Diphenyl-dihydro-furan-2-one 
• 37743-06-9 N-(tetrahydro-3,3-diphenyl-2-furylidene)methylamine hydrobromide 
• 50650-44-7 4-bromo-2,2-diphenylbutyric acid chloride 
• 37742-98-6 4-Bromo-2,2-diphenylbutyric acid 

Relevant academic research and scientific papers

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.

Synthesis and evaluation of [N-methyl-11C]N-desmethyl-loperamide as a new and improved PET radiotracer for imaging P-gp function

[11C]Loperamide has been proposed for imaging P-glycoprotein (P-gp) function with positron emission tomography (PET), but its metabolism to [N-methyl-11C]N-desmethyl-loperamide ([11C]dLop; [ 11C]3) precludes quantification. We considered that [11C]3 might itself be a superior radiotracer for imaging brain P-gp function and therefore aimed to prepare [11C]3 and characterize its efficacy. An amide precursor (2) was synthesized and methylated with [11C] iodomethane to give [11C]3. After administration of [11C]3 to wild-type mice, brain radioactivity uptake was very low. In P-gp (mdr-1a(-/-)) knockout mice, brain uptake of radioactivity at 30 min increased about 3.5-fold by PET measures, and over 7-fold by ex vivo measures. In knockout mice, brain radioactivity was predominantly (90%) unchanged radiotracer. In monkey PET experiments, brain radioactivity uptake was also very low but after P-gp blockade increased more than 7-fold. [11C]3 is an effective new radiotracer for imaging brain P-gp function and, in favor of future successful quantification, appears free of extensive brain-penetrant radiometabolites.