238418-67-2

Usage

Uses

Used in Medical Imaging:
D-Glutamine, 4-fluoro-, (4S)-rel(9CI) is used as a tracer in the field of medical imaging, specifically for positron emission tomography (PET). The application reason is to aid in the understanding of the phenomenon of cancer cells' strong requirement for glutamine, which can provide valuable insights into cancer biology and potentially lead to the development of targeted therapies.
Used in Cancer Research:
In the field of cancer research, D-Glutamine, 4-fluoro-, (4S)-rel(9CI) is used as a research tool to study the role of glutamine in cancer cell metabolism and its potential as a therapeutic target. The application reason is to explore the metabolic dependencies of cancer cells and identify novel strategies for cancer treatment by disrupting their glutamine metabolism.
Used in Drug Development:
D-Glutamine, 4-fluoro-, (4S)-rel(9CI) is also used in the development of new drugs targeting glutamine metabolism in cancer cells. The application reason is to create compounds that can inhibit glutamine utilization by cancer cells, thereby disrupting their growth and survival mechanisms, and potentially leading to more effective cancer treatments.

Upstream product

• 2358-03-4 erythro-4-fluoroglutamic acid 5-methyl ester 
• 26432-31-5 4-fluoroglutamic acid 
• 1262523-70-5 (2S,4R)-tert-butyl-2-(tert-butoxycarbonylamino)-4-fluoro-5-oxo-5-(2,4,6-trimethoxybenzylamino)pentanoate 
• 1262523-74-9 (2S,4S)-tert-butyl-2-(tert-butoxycarbonylamino)-4-fluoro-5-oxo-5-(2,4,6-trimethoxybenzylamino)pentanoate 
• 1262523-72-7 (2R,4R)-tert-butyl-2-(tert-butoxycarbonylamino)-4-fluoro-5-oxo-5-(2,4,6-trimethoxybenzylamino)pentanoate 
• 1262523-76-1 (2R,4S)-tert-butyl-2-(tert-butoxycarbonylamino)-4-fluoro-5-oxo-5-(2,4,6-trimethoxybenzylamino)pentanoate 

Relevant academic research and scientific papers

[18F](2S,4R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma

The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [18F]FDG-PET has some limitations and there is a portion of MM patients who are negative. Glutamine (Gln) addiction has been recently described as a typical metabolic feature of MM cells. Yet, the possible exploitation of Gln as a PET tracer in MM has never been assessed so far and is investigated in this study in preclinical models. Firstly, we have synthesized enantiopure (2S,4R)-4-fluoroglutamine (4-FGln) and validated it as a Gln transport analogue in human MM cell lines, comparing its uptake with that of 3H-labelled Gln. We then radiosynthesized [18F]4-FGln, tested its uptake in two different in vivo murine MM models, and checked the effect of Bortezomib, a proteasome inhibitor currently used in the treatment of MM. Both [18F]4-FGln and [18F]FDG clearly identified the spleen as site of MM cell colonization in C57BL/6 mice, challenged with syngeneic Vk12598 cells and assessed by PET. NOD.SCID mice, subcutaneously injected with human MM JJN3 cells, showed high values of both [18F]4-FGln and [18F]FDG uptake. Bortezomib significantly reduced the uptake of both radiopharmaceuticals in comparison with vehicle at post treatment PET. However, a reduction of glutaminolytic, but not of glycolytic, tumor volume was evident in mice showing the highest response to Bortezomib. Our data indicate that [18F](2S,4R)-4-FGln is a new PET tracer in preclinical MM models, yielding a rationale to design studies in MM patients.

Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging agents for tumors

A versatile synthetic route to prepare all four stereoisomeric 4-fluoro-glutamines was developed by exploiting a Passerini three-component reaction. The skeleton of 4-substituted glutamine derivatives was efficiently constructed. Subsequent four-step reactions, highlighted by a "neutralized" TASF fluorination, provided the desired products with high yields and excellent optical purity. The optically pure fluorine-18 labeled 4-fluoroglutamines were also successfully prepared using either a 18-crown-6/KHCO3 or K[222]/K2CO3 catalysis system. Preliminary cell uptake and inhibition studies using the 9L tumor cells ana SF188BC1-XL tumor cells (a glutamine addicted tumor derived from glioblastoma) provided strong evidence for their potential application in conjunction with positron emission tomography (PET) for in vivo imaging of tumors, which use glutamine as an alternative energy source.

SINGLE DIASTEREOMERS OF 4-FLUOROGLUTAMINE AND METHODS FO THEIR PREPARATION AND USE

The present invention is directed single diasteromers of 4-fluoroglutamine having a diastereomeric excess of at least 80%. Methods of preparing the single diastereomers are also described, as well as methods of using the single diastereomers of radiolabeled 4-fluoroglutamine as imaging agent is also described.

Chemistry of 4-fluoroglutamic acid. Part 3. Preparation of the diastereomers of 4-fluoroglutamine and 4-fluoroisoglutamine. An enzymatic access to the antipodes of 4-amino-2-fluorobutyric acid

The pure diastereomers of 4-fluoroglutamine and 4-fluoroisoglutamine were prepared from the corresponding 4-fluoroglutamic acids. Glutamic decarboxylase treatment of the acids led to chiral 2-fluoroGABA.