CGS-21680

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H29N7O6
Molecular Weight	499.5197
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCNC(=O)[C@H]1O[C@H]([C@H](O)[C@@H]1O)N2C=NC3=C2N=C(NCCC4=CC=C(CCC(O)=O)C=C4)N=C3N

InChI

InChIKey=PAOANWZGLPPROA-RQXXJAGISA-N

InChI=1S/C23H29N7O6/c1-2-25-21(35)18-16(33)17(34)22(36-18)30-11-27-15-19(24)28-23(29-20(15)30)26-10-9-13-5-3-12(4-6-13)7-8-14(31)32/h3-6,11,16-18,22,33-34H,2,7-10H2,1H3,(H,25,35)(H,31,32)(H3,24,26,28,29)/t16-,17+,18-,22+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2795469 | https://www.ncbi.nlm.nih.gov/pubmed/2600819
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800000147

CGS -21680 is an adenosine A2 receptor agonist with IC50 of 22 nM, exhibits 140-fold over A1 receptor. In an isolated perfused working rat heart model, CGS -21680 effectively increases coronary flow with an ED25 value of 1.8 nM. CGS-21680 binds adenosine A2 receptor with high affinity (Kd = 15.5 nM). Novartis originated CGS- 21680 in Switzerland and discontinued its development later.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adenosine A2a receptor 30 Target ID: CHEMBL251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25780876 \| https://www.ncbi.nlm.nih.gov/pubmed/25221664 \| https://www.ncbi.nlm.nih.gov/pubmed/2795469	Agonist 2678		18.47 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: http://adisinsight.springer.com/drugs/800000147 https://www.ncbi.nlm.nih.gov/pubmed/11877342	Primary		Preclinical	Unknown Approved Use Unknown
Myocardial ischemia 15 Sources: http://adisinsight.springer.com/drugs/800000147 https://www.ncbi.nlm.nih.gov/pubmed/21044214 https://www.ncbi.nlm.nih.gov/pubmed/20709859 https://www.ncbi.nlm.nih.gov/pubmed/15821439	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
[3H]CGS 21680, a selective A2 adenosine receptor agonist directly labels A2 receptors in rat brain.	1989 Dec	2600819
Site-directed mutagenesis identifies residues involved in ligand recognition in the human A2a adenosine receptor.	1995 Jun 9	7775460
Neonatal capsaicin attenuates mechanical nociception in the rat.	1996 Feb 23	8907337
Selective adenosine A2A receptor/dopamine D2 receptor interactions in animal models of schizophrenia.	1996 Jan 11	8720578
Mechanism and pressor relevance of the short-term cardiovascular and renin excitatory actions of the selective A2A-adenosine receptor agonists.	1997 Sep	9300315
Differences in the order of potency for agonists but not antagonists at human and rat adenosine A2A receptors.	1999 Jan 1	9920286
Why are A(2B) receptors low-affinity adenosine receptors? Mutation of Asn273 to Tyr increases affinity of human A(2B) receptor for 2-(1-Hexynyl)adenosine.	2000 Dec	11093773
The role of the D(2) dopamine receptor (D(2)R) in A(2A) adenosine receptor (A(2A)R)-mediated behavioral and cellular responses as revealed by A(2A) and D(2) receptor knockout mice.	2001 Feb 13	11172060
Cocaine-induced hyperactivity is more influenced by adenosine receptor agonists than amphetamine-induced hyperactivity.	2002 Jul-Aug	12523489
Impaired D2 dopamine receptor function in mice lacking type 5 adenylyl cyclase.	2002 Sep 15	12223546
Distinct protein kinase C isoforms mediate regulation of vascular endothelial growth factor expression by A2A adenosine receptor activation and phorbol esters in pheochromocytoma PC12 cells.	2003 Apr 25	12590138
2-Substituted adenosine derivatives: affinity and efficacy at four subtypes of human adenosine receptors.	2004 Nov 15	15476669
Modulation of seizures and synaptic plasticity by adenosinergic receptors in an experimental model of temporal lobe epilepsy induced by pilocarpine in rats.	2005	15987273
Participation of adenosine system in the ketamine-induced motor activity in mice.	2005 Jan-Feb	15849377
A novel A1 adenosine receptor antagonist, L-97-1 [3-[2-(4-aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], reduces allergic responses to house dust mite in an allergic rabbit model of asthma.	2005 Oct	16020631
Evidence for both adenosine A1 and A2A receptors activating single vagal sensory C-fibres in guinea pig lungs.	2006 Sep 1	16793905
Pharmacological characterization of a novel, potent adenosine A1 and A2A receptor dual antagonist, 5-[5-amino-3-(4-fluorophenyl)pyrazin-2-yl]-1-isopropylpyridine-2(1H)-one (ASP5854), in models of Parkinson's disease and cognition.	2007 Nov	17684118
Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages.	2008 Dec	19035488
Compensatory upregulation of the adenosine system following phenylephrine-induced hypertrophy in cultured rat ventricular myocytes.	2010 Feb	19966059
Adenosine up-regulates vascular endothelial growth factor in human macrophages.	2010 Feb 12	20067761
Adenosine reduces cell surface expression of toll-like receptor 4 and inflammation in response to lipopolysaccharide and matrix products.	2011 Dec	21538184
A novel fused 1,2,4-triazine aryl derivative as antioxidant and nonselective antagonist of adenosine A(2A) receptors in ethanol-activated liver stellate cells.	2012 Jan 5	22063920

Patents

Sample Use Guides

In Vivo Use Guide

CGS-21680 is active p.o. in the spontaneously hypertensive rat at a dose of 10 mg/kg with efficacy for up to 24 hr.

Route of Administration: Oral

In Vitro Use Guide

CGS-21680 (100 nM) inhibited non-inactivating K+ current (IAC) by 78.4 +/- 4.6 % in bovine adrenal cortical cells.

Name

Type

Language

CGS-21680

Common Name

English

BENZENEPROPANOIC ACID, 4-(2-((6-AMINO-9-(N-ETHYL-.BETA.-D-RIBOFURANURONAMIDOSYL)-9H-PURIN-2-YL)AMINO)ETHYL)-

Systematic Name

English

2-(4-(2-CARBOXYETHYL)PHENETHYLAMINO)-5'-N- ETHYLCARBOXAMIDOADENOSINE

Common Name

English

Code System Code Type Description

PUBCHEM

3086599