Syntheses and in vitro biological evaluation of S1PR1 ligands and PET studies of four F-18 labeled radiotracers in the brain of nonhuman primates

Literature Information

Publication Date 2018-11-15
DOI 10.1039/C8OB02609B
Impact Factor 3.876
Authors

Zonghua Luo, Junbin Han, Hui Liu, Adam J. Rosenberg, Delphine L. Chen, Robert J. Gropler, Zhude Tu


View Original

Abstract

A series of seventeen hydroxyl-containing sphingosine 1-phosphate receptor 1 (S1PR1) ligands were designed and synthesized. Their in vitro binding potencies were determined using [32P]S1P competitive binding assays. Compounds 10a, 17a, 17b, and 24 exhibited high S1PR1 binding potencies with IC50 values ranging from 3.9 to 15.4 nM and also displayed high selectivity for S1PR1 over other S1P receptor subtypes (IC50 > 1000 nM for S1PR2–5). The most potent compounds 10a, 17a, 17b, and 24 were subsequently radiolabeled with F-18 in high yields and purities. MicroPET studies in cynomolgus macaque showed that [18F]10a, [18F]17a, and [18F]17b but not [18F]24 crossed the blood brain barrier and had high initial brain uptake. Further validation of [18F]10a, [18F]17a, and [18F]17b in preclinical models of neuroinflammation is warranted to identify a suitable PET radioligand to quantify S1PR1 expression in vivo as a metric of an inflammatory response.

Related Literature

Contents list

Front/Back Matter

DOI: 10.1039/C7CP90200J

Catalytic mechanism of phenylacetone monooxygenases for non-native linear substrates

Miguel de Abreu, Lyndsey J. Ferguson, Derek J. Quinn, Thomas S. Moody, Meilan Huang

2017-09-07 Paper

DOI: 10.1039/C7CP03640J

Revealing the correlation between charge carrier recombination and extraction in an organic solar cell under varying illumination intensity

Mihirsinh Chauhan, Vishal Bharti, Manoj Kumar, Suresh Chand, Brijesh Tripathi, J. P. Tiwari

2017-09-04 Paper

DOI: 10.1039/C7CP05235A

Running out of lithium? A route to differentiate between capacity losses and active lithium losses in lithium-ion batteries

Florian Holtstiege, Andrea Wilken, Tobias Placke

2017-09-12 Paper

DOI: 10.1039/C7CP05405J

Developing an efficient NiCo2S4 cocatalyst for improving the visible light H2 evolution performance of CdS nanoparticles

Junwen Peng, Junli Xu, Zhaoyu Wang, Zhengxin Ding, Sibo Wang

2017-09-11 Paper

DOI: 10.1039/C7CP05147F

Contents list

Front/Back Matter

DOI: 10.1039/C7CP90212C

A lipophilic ionic liquid based on formamidinium cations and TFSI: the electric response and the effect of CO2 on the conductivity mechanism

Federico Bertasi, Guinevere A. Giffin, Keti Vezzù, Yaser Abu-Lebdeh, Michel Armand

2017-09-05 Paper

DOI: 10.1039/C7CP02304A

Structural relaxation, viscosity, and network connectivity in a hydrogen bonding liquid

Georg Ehlers, Joerg C. Neuefeind, Souleymane O. Diallo, Christopher B. Stanley, Luke Daemen

2017-07-21 Paper

DOI: 10.1039/C7CP04013J

Self-assembly of diphenylalanine with preclick components as capping groups

Andrea Gemma, Gema Ballano, Juan Torras, Ana I. Jiménez, Carlos Cativiela

2017-09-11 Paper

DOI: 10.1039/C7CP03792A

You might also like

Compound Q&A

What is 3-Fluoro-2-methylbenzylamine (CAS: 771573-36-5)?

3-Fluoro-2-methylbenzylamine is an organic compound with the CAS number 771573-3...

771573-36-53-Fluoro-2-methylben...
Compound Q&A

Is Tert-butyl 2-(oxetan-3-ylidene)acetate (CAS: 1207175-03-8) safe?

Tert-butyl 2-(oxetan-3-ylidene)acetate is considered safe for its intended uses ...

1207175-03-8Tert-butyl 2-(oxetan...
Compound Q&A

What precautions should be taken when handling 4-Acetyl-2-fluorobenzonitrile (CAS: 214760-18-6)?

Proper personal protective equipment (PPE) such as gloves, goggles, and a lab co...

214760-18-64-Acetyl-2-fluoroben...
Compound Q&A

How is 2-Ethyl-4-methyl-1,3-thiazole (CAS: 15679-12-6) typically synthesized?

2-Ethyl-4-methyl-1,3-thiazole is commonly synthesized via the reaction of thiour...

15679-12-62-Ethyl-4-methyl-1,3...
Compound Q&A

How should 5',5''-([2,2'-Bithiophene]-5,5'-diyl)bis(([1,1':3',1''-terphenyl]-4,4''-dicarboxylic acid)) (CAS: 1227780-71-3) be stored?

This compound should be stored in a cool, dry place away from direct sunlight an...

1227780-71-35',5''''-([2,2'-Bith...
Compound Q&A

What regulatory guidelines apply to L-Lysine Acetate Salt (CAS: 52315-92-1)?

L-Lysine Acetate Salt (CAS: 52315-92-1) is subject to various regulatory guideli...

52315-92-1L-LYSINE ACETATE SAL...
Compound Q&A

Is 6-Fluoro-3-hydroxy-2-pyrazinecarboxamide (CAS: 259793-96-9) safe?

6-Fluoro-3-hydroxy-2-pyrazinecarboxamide (CAS: 259793-96-9) is generally conside...

259793-96-96-Fluoro-3-hydroxy-2...
Compound Q&A

What are the physical and chemical properties of 1,1'-Sulfonylbis(1H-imidazole) (CAS: 7189-69-7)?

1,1'-Sulfonylbis(1H-imidazole) is a crystalline solid with a molecular weight of...

7189-69-71,1'-Sulfonylbis(1H-...
Compound Q&A

What industries use 4-methyl-7-nitro-1H-indole-3-carbonitrile (CAS: 289483-82-5)?

4-Methyl-7-nitro-1H-indole-3-carbonitrile (CAS: 289483-82-5) is primarily used i...

289483-82-54-methyl-7-nitro-1H-...
Compound Q&A

How should waste containing 5-Bromo-3-indolyl-beta-galactoside (CAS: 97753-82-7) be handled?

Waste containing 5-Bromo-3-indolyl-beta-galactoside (CAS: 97753-82-7) should be ...

97753-82-75-Bromo-3-indolyl-be...

Source Journal

Organic & Biomolecular Chemistry

Organic & Biomolecular Chemistry
CiteScore: 3.4
Self-citation Rate: 10.3%
Articles per Year: 1041

Organic & Biomolecular Chemistry (OBC) publishes original and high impact research and reviews in organic chemistry. We welcome research that shows new or significantly improved protocols or methodologies in total synthesis, synthetic methodology or physical and theoretical organic chemistry as well as research that shows a significant advance in the organic chemistry or molecular design aspects of chemical biology, catalysis, supramolecular and macromolecular chemistry, theoretical chemistry, mechanism-oriented physical organic chemistry, medicinal chemistry or natural products. Articles published in the journal should report new work which makes a highly-significant impact in the field. Routine and incremental work is generally not suitable for publication in the journal. More details about key areas of our scope are below. In all cases authors should include in their article clear rationale for why their research has been carried out.

Recommended Compounds

Recommended Suppliers

Disclaimer
This page provides academic journal information for reference and research purposes only. We are not affiliated with any journal publishers and do not handle publication submissions. For publication-related inquiries, please contact the respective journal publishers directly.
If you notice any inaccuracies in the information displayed, please contact us at support@chemtradehub.com. We will promptly review and address your concerns.