Synthesis and evaluation of two positron-labeled nitric oxide synthase inhibitors, S-[11C]methylisothiourea and S-(2-[18F]fluoroethyl)isothiourea, as potential positron emission tomography tracers

Journal of Medicinal Chemistry
J ZhangM J Welch

Abstract

In an effort to develop a tracer for probing inducible nitric oxide synthase (iNOS) levels in vivo utilizing positron emission tomography, we have synthesized and evaluated two positron-emitting iNOS selective inhibitors: S-[11C]methylisothiourea (1b) and S-(2-[18F]fluoroethyl)-isothiourea (3b). Prior to fluorine-18 labeling, the nonradioactive fluoro derivative S-(2-fluoroethyl)isothiourea (3a) was prepared and determined to have a 9-fold higher selectivity for iNOS compared to endothelial NOS (eNOS). Radiochemical synthesis of both compounds, in high radiochemical purity and at high specific activity, was accomplished by the S-alkylation reaction of labeled precursors (11CH3I or 18FCH2CH2OTf) with thiourea. An in vitro model, J774 macrophage cell line, was used to assess the uptake of radiolabeled iNOS inhibitor in response to iNOS induction at the cellular level. Increased cell uptake of these two labeled compounds at stimulated iNOS levels, as well as blocking under controlled in vitro conditions, was observed. Lipophilicity (log P o/w), stability, and tissue biodistribution data of both compounds are reported. Serum stability studies indicate that 3b metabolized much more rapidly compared to the relatively stable 1b in vit...Continue Reading

References

Mar 20, 1992·Journal of Medicinal Chemistry·N M Olken, M A Marletta
Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T EvansJ Cohen
Apr 10, 1992·Science·D B KabackJ W Mahon
Apr 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·A GjeddeH Kuwabara
Nov 15, 1990·Biochemical and Biophysical Research Communications·R G KilbournR F Lodato
Jan 1, 1989·International Journal of Radiation Applications and Instrumentation. Part A, Applied Radiation and Isotopes·D O KiesewetterR D Finn
Apr 29, 1994·Biochemical and Biophysical Research Communications·A R Baydoun, G E Mann
Nov 11, 1994·Journal of Medicinal Chemistry·W M MooreM G Currie
Jan 1, 1995·British Journal of Pharmacology·G J SouthanC Thiemermann
Sep 1, 1995·The American Journal of Physiology·R G BogleP Vallance
Mar 16, 1993·European Journal of Pharmacology·T P MiskoM G Currie
Oct 15, 1993·Biochemical and Biophysical Research Communications·A RojasM Palacios

❮ Previous
Next ❯

Citations

Sep 16, 1998·Current Opinion in Chemical Biology·B R Babu, O W Griffith
Oct 2, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Fabien ChauveauBertrand Tavitian
Sep 10, 2014·Neuroscience·H AmhaoulS Dedeurwaerdere
Dec 17, 2008·Dalton Transactions : an International Journal of Inorganic Chemistry·Bruno L OliveiraAna P Freire
Dec 1, 2006·American Journal of Pharmaceutical Education·Andrew A Webster, Robert M Riggs
Dec 1, 2006·American Journal of Pharmaceutical Education·Naser Z AlsharifAlaba M Ogunbadeniyi
Jul 9, 2002·Journal of Combinatorial Chemistry·Alan R KatritzkyBehrouz Forood
Jan 7, 2004·American Journal of Surgery·Shouiti UenoyamaTeruhisa Kazui
Apr 17, 2001·The Journal of Organic Chemistry·A R KatritzkyB Insuasty

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]
E R PettipherR J Griffiths
The Journal of Pharmacy and Pharmacology
Ramakrishna NirogiMohammed Abdul Rasheed
© 2022 Meta ULC. All rights reserved