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

Molecular Formula	C23H29N7O6
Molecular Weight	499.5197
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

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
Binding of the adenosine A2 receptor ligand [3H]CGS 21680 to human and rat brain: evidence for multiple affinity sites.	1990 Nov	2213023
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
Comparative pharmacology of human adenosine receptor subtypes - characterization of stably transfected receptors in CHO cells.	1998 Jan	9459566
Differences in the order of potency for agonists but not antagonists at human and rat adenosine A2A receptors.	1999 Jan 1	9920286
Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP.	1999 Nov	10591873
Characterization of human A(2B) adenosine receptors: radioligand binding, western blotting, and coupling to G(q) in human embryonic kidney 293 cells and HMC-1 mast cells.	1999 Oct	10496952
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
[(3)H]MRE 3008F20: a novel antagonist radioligand for the pharmacological and biochemical characterization of human A(3) adenosine receptors.	2000 May	10779381
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
Neuroprotective effect of L-DOPA co-administered with the adenosine A2A receptor agonist CGS 21680 in an animal model of Parkinson's disease.	2004 Aug 30	15342103
Synthesis and biological activity of new potential agonists for the human adenosine A2A receptor.	2004 Jul 29	15267242
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
Inhibition of phenylephrine-induced cardiomyocyte hypertrophy by activation of multiple adenosine receptor subtypes.	2005 Jan	15452191
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
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
Hyperalgesia, low-anxiety, and impairment of avoidance learning in neonatal caffeine-treated rats.	2007 Mar	17096081
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
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
Adenosine receptor agonists attenuate the development of diazepam withdrawal-induced sensitization in mice.	2008 Jun 24	18466897
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
Adenosine A2A receptor and TNF-α regulate the circadian machinery of the human monocytic THP-1 cells.	2013 Feb	22923002
Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism.	2015 Nov 15	26367767

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 18:11:53 GMT 2023` Edited by `admin` on `Fri Dec 15 18:11:53 GMT 2023`
Record UNII	T5HB1E831H
Record Status	`Validated (UNII)`
Record Version

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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