PMID: 11906291Mar 22, 2002Paper

1,8-disubstituted xanthine derivatives: synthesis of potent A2B-selective adenosine receptor antagonists

Journal of Medicinal Chemistry
Alaa M HayallahC E Müller

Abstract

3-Unsubstituted xanthine derivatives bearing a cyclopentyl or a phenyl residue in the 8-position were synthesized and developed as A2B adenosine receptor antagonists. Compounds bearing polar substituents were prepared to obtain water-soluble derivatives. 1-Alkyl-8-phenylxanthine derivatives were found to exhibit high affinity for A2B adenosine receptors (ARs). 1,8-disubstituted xanthine derivatives were equipotent to or more potent than 1,3,8-trisubstituted xanthines at A2B ARs, but generally less potent at A1 and A2A, and much less potent at A3 ARs. Thus, the new compounds exhibited increased A2B selectivity versus all other AR subtypes. 9-Deazaxanthines (pyrrolo[2,3-d]pyrimidindiones) appeared to be less potent at A2B ARs than the corresponding xanthine derivatives. 1-Propyl-8-p-sulfophenylxanthine (17) was the most selective compound of the present series, exhibiting a K(i) value of 53 nM at human A2B ARs and showing greater than 180-fold selectivity versus human A1 ARs. Compound 17 was also highly selective versus rat A1 ARs (41-fold) and versus the other human AR subtypes (A2A > 400-fold and A3 > 180-fold). The compound is highly water-soluble due to its sulfonate function. 1-Butyl-8-p-carboxyphenylxanthine (10), another p...Continue Reading

References

Feb 18, 1992·Biochemical Pharmacology·J BaumgoldK A Jacobson
May 1, 1984·Naunyn-Schmiedeberg's Archives of Pharmacology·M J LohseU Schwabe
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·C A SalvatoreR G Johnson
Jul 1, 1993·British Journal of Pharmacology·M F GurdenC J Vardey
Mar 7, 1998·Journal of Neuroscience Methods·K FinlaysonH J Olverman
Jun 5, 1998·Trends in Pharmacological Sciences·I FeoktistovI Biaggioni
Jul 29, 1998·Bioorganic & Medicinal Chemistry·C E MüllerK N Klotz
Dec 9, 2000·Naunyn-Schmiedeberg's Archives of Pharmacology·K N Klotz
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·J Linden

❮ Previous
Next ❯

Citations

Feb 8, 2005·Psychopharmacology·Marcello SolinasSteven R Goldberg
May 17, 2003·European Journal of Medicinal Chemistry·Anna DrabczyńskaKatarzyna Kieć-Kononowicz
Jun 2, 2011·Chemical & Pharmaceutical Bulletin·Rashad Al-SalahiMaria Koellner
Jan 30, 2016·Journal of Medicinal Chemistry·Abdelaziz El MaatouguiEddy Sotelo
Oct 26, 2005·Il Farmaco·Barkin BerkKenneth A Jacobson
Sep 1, 2004·Bioorganic & Medicinal Chemistry·Anna DrabczyńskaKatarzyna Kieć-Kononowicz
Jul 19, 2012·Chemistry : a European Journal·Bo LiuJingsong You
Feb 7, 2014·Chemistry : a European Journal·Dong XueJianliang Xiao
Jul 19, 2006·Medicinal Research Reviews·Margot W BeukersAdriaan P Ijzerman
Mar 9, 2005·British Journal of Pharmacology·Mojtaba PanjehpourKarl-Norbert Klotz
Aug 2, 2007·Medicinal Research Reviews·Maykel Pérez GonzálezMarta Teijeira
Dec 29, 2005·Medicinal Research Reviews·Stefano MoroGiampiero Spalluto
Mar 3, 2007·The Journal of Pharmacy and Pharmacology·D RüsingE J Verspohl
Feb 13, 2014·British Journal of Pharmacology·Stephen P H AlexanderUNKNOWN CGTP Collaborators
Oct 18, 2003·The Journal of Pharmacology and Experimental Therapeutics·Osama M Abo-SalemChrista E Müller
Mar 19, 2014·The Journal of Pharmacology and Experimental Therapeutics·Sonja HinzChrista E Müller
Mar 5, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mengnan WangYouzhong An
Jan 13, 2011·Chemistry : a European Journal·Chau Ming SoFuk Yee Kwong
Nov 5, 2011·Chemistry : a European Journal·Bo LiuJingsong You
Jul 25, 2019·Current Pharmaceutical Design·Balakumar ChandrasekaranNikhil Agrawal
Jun 12, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniel MarxChrista E Müller
Dec 28, 2010·Biochimica Et Biophysica Acta·Christa E Müller, Kenneth A Jacobson

❮ 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.