Bioorg Med Chem Lett. 2008 Jul 15;18(14):4199-203. Epub 2008 May 22.

Biaryl and heteroaryl derivatives of SCH 58261 as potent and selective adenosine A2A receptor antagonists.

Shah U, Boyle CD, Chackalamannil S, Neustadt BR, Lindo N, Greenlee WJ, Foster C, Arik L, Zhai Y, Ng K, Wang S, Monopoli A, Lachowicz JE.

Source

Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.

Abstract

SCH 58261 is a reported adenosine A(2A) receptor antagonist, which is active in rat in vivo models of Parkinson's Disease upon ip administration. However, it has poor selectivity versus the A(1) receptor and does not demonstrate oral activity. We report the design and synthesis of biaryl and heteroaryl analogs of SCH 58261 which improve the A(2A) receptor binding selectivity as well as the pharmacokinetic properties of SCH 58261. In particular, the quinoline 25 has excellent A(2A) receptor in vitro binding affinity and selectivity, sustained rat plasma levels upon oral dosing, and is active orally in a rat behavioral assay.

PMID:: 18562199; [PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Chemical Information

BindingDB

Medical

Parkinson's Disease - MedlinePlus Health Information

Supplemental Content

Save items

Related citations in PubMed

Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists. [Bioorg Med Chem Lett. 2008]
Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists.
Shah U, Lankin CM, Boyle CD, Chackalamannil S, Greenlee WJ, Neustadt BR, Cohen-Williams ME, Higgins GA, Ng K, Varty GB, et al. Bioorg Med Chem Lett. 2008 Jul 15; 18(14):4204-9. Epub 2008 May 22.
Potent and selective adenosine A2A receptor antagonists: 1,2,4-Triazolo[1,5-c]pyrimidines. [Bioorg Med Chem Lett. 2009]
Potent and selective adenosine A2A receptor antagonists: 1,2,4-Triazolo[1,5-c]pyrimidines.
Neustadt BR, Liu H, Hao J, Greenlee WJ, Stamford AW, Foster C, Arik L, Lachowicz J, Zhang H, Bertorelli R, et al. Bioorg Med Chem Lett. 2009 Feb 1; 19(3):967-71. Epub 2008 Nov 24.
Novel bicyclic piperazine derivatives of triazolotriazine and triazolopyrimidines as highly potent and selective adenosine A2A receptor antagonists. [J Med Chem. 2004]
Novel bicyclic piperazine derivatives of triazolotriazine and triazolopyrimidines as highly potent and selective adenosine A2A receptor antagonists.
Peng H, Kumaravel G, Yao G, Sha L, Wang J, Van Vlijmen H, Bohnert T, Huang C, Vu CB, Ensinger CL, et al. J Med Chem. 2004 Dec 2; 47(25):6218-29.
Review Selective adenosine A2A receptor antagonists. [Farmaco. 2001]
Review Selective adenosine A2A receptor antagonists.
Ongini E, Monopoli A, Cacciari B, Baraldi PG. Farmaco. 2001 Jan-Feb; 56(1-2):87-90.
Review [Is the inhibition of adenosine A(2A) receptors an efficient way of Parkinson's disease treatment?]. [Neurol Neurochir Pol. 2006]
Review [Is the inhibition of adenosine A(2A) receptors an efficient way of Parkinson's disease treatment?].
Ceiślak M, Komoszyński M. Neurol Neurochir Pol. 2006 May-Jun; 40(3):219-26.

See reviews... See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
BioAssay
PubChem BioAssay experiments on the biological activities of small molecules that cite the current articles. The depositors of BioAssay data provide these references.
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.

Recent activity

Clear Turn Off Turn On

Biaryl and heteroaryl derivatives of SCH 58261 as potent and selective adenosine...
Biaryl and heteroaryl derivatives of SCH 58261 as potent and selective adenosine A2A receptor antagonists.
Bioorg Med Chem Lett. 2008 Jul 15 ;18(14):4199-203. Epub 2008 May 22 .

PubMed
Relationships between behavior, brainstem and cortical encoding of seen and hear...
Relationships between behavior, brainstem and cortical encoding of seen and heard speech in musicians and non-musicians.
Hear Res. 2008 Jul ;241(1-2):34-42. Epub 2008 May 17 .

PubMed
SB203580, a p38 mitogen-activated protein kinase inhibitor, fails to improve fun...
SB203580, a p38 mitogen-activated protein kinase inhibitor, fails to improve functional outcome following a moderate spinal cord injury in rat.
Neuroscience. 2008 Jul 31 ;155(1):128-37. Epub 2008 May 17 .

PubMed
Comparative toxicokinetics and metabolism of rebaudioside A, stevioside, and ste...
Comparative toxicokinetics and metabolism of rebaudioside A, stevioside, and steviol in rats.
Food Chem Toxicol. 2008 Jul ;46 Suppl 7:S31-9. Epub 2008 May 16 .

PubMed
Seeking refuge from violence in street-based drug scenes: women's experiences in...
Seeking refuge from violence in street-based drug scenes: women's experiences in North America's first supervised injection facility.
Soc Sci Med. 2008 Sep ;67(5):817-23. Epub 2008 Jun 16 .

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to:

Biaryl and heteroaryl derivatives of SCH 58261 as potent and selective adenosine A2A receptor antagonists.

Source

Abstract

MeSH Terms, Substances

MeSH Terms

Substances

LinkOut - more resources

Full Text Sources

Chemical Information

Medical

Supplemental Content

Save items

Related citations in PubMed

Related information

Recent activity

Simple NCBI Directory

Getting Started

Resources

Popular

Featured

NCBI Information