66164-06-5

Usage

Uses

Used in Pharmaceutical Industry:
N-Didesmethyl Loperamide is used as a new and improved PET (Positron Emission Tomography) radiotracer for imaging P-gp (P-glycoprotein) function. P-glycoprotein is a membrane protein that acts as an efflux pump, playing a crucial role in multidrug resistance in cancer cells. The use of N-Didesmethyl Loperamide as a PET radiotracer allows for better visualization and understanding of P-gp function, which can lead to the development of more effective cancer treatments.
Used in Medical Imaging:
In the field of medical imaging, N-Didesmethyl Loperamide serves as a valuable tool for researchers and clinicians. Its role as a PET radiotracer enables the assessment of P-gp function in various tissues and organs, providing insights into the mechanisms of drug resistance and the potential for personalized treatment strategies. This application can significantly impact the diagnosis and management of various diseases, particularly cancer.
Used in Drug Development:
N-Didesmethyl Loperamide's unique properties also make it a promising candidate for drug development. Its ability to target and image P-gp function can be leveraged to design and develop novel therapeutic agents that can overcome multidrug resistance in cancer cells. This can lead to the creation of more effective drugs with fewer side effects, ultimately improving patient outcomes and quality of life.

InChI:InChI=1/C27H29ClN2O2/c28-24-13-11-21(12-14-24)26(32)15-18-30(19-16-26)20-17-27(25(29)31,22-7-3-1-4-8-22)23-9-5-2-6-10-23/h1-14,32H,15-20H2,(H2,29,31)

Upstream product

• 39512-49-7 4-(4-chlorophenyl)-4-hydroxypiperidine 
• 39186-58-8 4-bromo-2,2-diphenylbutyronitrile 
• 63959-33-1 VUF 5742 

Downstream Products

• 1067642-12-9 [¹¹C]N-desmethylloperamide 
• 66164-07-6 Desmethylloperamide 
• 1424272-65-0 4-(4-(4-chlorophenyl)-4-hydroxypiperidine-1-yl)-N-(3-fluoropropyl)-2,2-diphenylbutanamide 
• 1424272-64-9 4-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-N-(2-fluoroethyl)-2,2-diphenylbutanamide 
• 1424272-67-2 11-(4-chlorophenyl)-4,4-diphenyl-10-oxa-1,6-diazabicyclo[9.2.2]pentadecan-5-one 
• 1424272-68-3 [N-ethyl-¹⁸F]-N-desmethylloperamide 

Relevant academic research and scientific papers

Overcoming chloroquine resistance in malaria: Design, synthesis and structure-activity relationships of novel chemoreversal agents

Malaria remains a significant infectious disease with even artemisinin-based therapies now facing resistance in the field. Development of new therapies is urgently needed, either by finding new compounds with unique modes of action, or by reversing resistance towards known drugs with 'chemosensitizers' or 'chemoreversal' agents (CRA). Concerning the latter, we have focused on the resistance mechanisms developed against chloroquine (CQ). We have synthesized a series of compounds related to previously identified CRAs, and found promising novel compounds. These compounds show encouraging results in a coumarin labeled chloroquine uptake assay, exhibiting a dose response in resensitising parasites to the antimalarial effects of chloroquine. Selected compounds show consistent potency across a panel of chloroquine and artemisinin sensitive and resistant parasites, and a wide therapeutic window. This data supports further study of CRAs in the treatment of malaria and, ultimately, their use in chloroquine-based combination therapies.

Radiosynthesis of 18F-labeled N-desmethyl-loperamide analogues for prospective molecular imaging radiotracers

A simple procedure for preparing fluoroethyl-N-desmethyl-loperamide 4 and its analogue 5 was developed. Standard compound 4 was synthesized in useful yields for radiolabeling analysis. [N-Ethyl-18F]N-desmethyl-loperamide, 3, was rapidly and efficiently labeled with no-carrier added fluorine-18 (t 1/2 = 109.7 min) by treatment of readily prepared [ 18F]1-bromo-2-fluoro ethane with a N-desmethyl-loperamide precursor at a consistent 7% radiochemical yield. This procedure was also adapted to the radiosynthesis of 3 by [18F]ethylene tosylate, but at a lower 3% radiochemical yield. Copyright

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

RADIOTRACERS FOR IMAGING P-GLYCOPROTEIN FUNCTION

P-glycoprotein transporter (P-gp) acts as a pump at the blood-brain barrier to exclude a wide range of xenobiotics (e.g., toxins, drugs, etc.) from the brain and is also expressed in a tumor in response to exposure to established or prospective chemothera

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.