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
Binding of the adenosine A2 receptor ligand [3H]CGS 21680 to human and rat brain: evidence for multiple affinity sites.	1990 Nov	2213023
KF17837: a novel selective adenosine A2A receptor antagonist with anticataleptic activity.	1994 May 2	8045270
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
Evidence against a major role of adenosine in oxygen-dependent regulation of erythropoietin in rats.	1997 Aug	9263988
Characterization of human A2A adenosine receptors with the antagonist radioligand [3H]-SCH 58261.	1997 Jun	9179373
Adenosine A2 receptors modulate haloperidol-induced catalepsy in rats.	1997 Jun 11	9218695
Mechanism and pressor relevance of the short-term cardiovascular and renin excitatory actions of the selective A2A-adenosine receptor agonists.	1997 Sep	9300315
Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP.	1999 Nov	10591873
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
Influence of adenosine receptor agonists on benzodiazepine withdrawal signs in mice.	2005 Oct 31	16226742
Adenosine A(2A) receptors play a role in the pathogenesis of hepatic cirrhosis.	2006 Aug	16783407
Adenosine receptors as therapeutic targets.	2006 Mar	16518376
Evidence for both adenosine A1 and A2A receptors activating single vagal sensory C-fibres in guinea pig lungs.	2006 Sep 1	16793905
Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages.	2008 Dec	19035488
Brainstem phosphorylated extracellular signal-regulated kinase 1/2-nitric-oxide synthase signaling mediates the adenosine A2A-dependent hypotensive action of clonidine in conscious aortic barodenervated rats.	2008 Jan	17934014
Absence of adenosine-mediated aortic relaxation in A(2A) adenosine receptor knockout mice.	2009 Nov	19749167
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