EFAROXAN

Details

Stereochemistry	RACEMIC
Molecular Formula	C13H16N2O
Molecular Weight	216.2789
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1(CC2=C(O1)C=CC=C2)C3=NCCN3

InChI

InChIKey=RATZLMXRALDSJW-UHFFFAOYSA-N

InChI=1S/C13H16N2O/c1-2-13(12-14-7-8-15-12)9-10-5-3-4-6-11(10)16-13/h3-6H,2,7-9H2,1H3,(H,14,15)

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800000035 | https://www.ncbi.nlm.nih.gov/pubmed/12798376 | https://www.ncbi.nlm.nih.gov/pubmed/20504687 | https://www.ncbi.nlm.nih.gov/pubmed/1687123

Efaroxan (RX 821037) is a potent and selective alpha(2)-adrenoceptor antagonist. Additionally, Efaroxan is a selective antagonist at the imidazoline I1 receptor. Efaroxan promotes insulin secretion, in the absence of exogenous agonists, by a mechanism that involves inhibition of ATP-regulated K+ channels. Efaroxan was in clinical trials for the treatment of diabetes mellitus however its development has been discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Alpha-2a adrenergic receptor 63 Target ID: CHEMBL1867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27265687 \| https://www.ncbi.nlm.nih.gov/pubmed/23376415 \| https://www.ncbi.nlm.nih.gov/pubmed/14716222	Antagonist 2778		4.4 nM [Ki]
Nischarin 7 Target ID: CHEMBL3923 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18621536 \| https://www.ncbi.nlm.nih.gov/pubmed/23166584	Antagonist 2778		52.36 nM [Ki]

PubMed

Title	Date	PubMed
Blockade by agmatine of catecholamine release from chromaffin cells is unrelated to imidazoline receptors.	2001 Apr 6	11301064
The I1-imidazoline receptor in PC12 pheochromocytoma cells activates protein kinases C, extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK).	2001 Dec	11739604
Interactions of ligands at angiotensin II-receptors and imidazoline receptors.	2001 Feb	11286399
Imidazoline I(1) receptor-induced activation of phosphatidylcholine-specific phospholipase C elicits mitogen-activated protein kinase phosphorylation in PC12 cells.	2001 Mar	11274989
Specific desensitization of sulfonylurea- but not imidazoline-induced insulin release after prolonged tolbutamide exposure.	2001 Mar 1	11239495
The potential antidiabetic activity of some alpha-2 adrenoceptor antagonists.	2001 Nov	11712871
Evidence for the involvement of central I1 imidazoline receptor in ethanol counteraction of clonidine hypotension in spontaneously hypertensive rats.	2001 Sep	11486246
Presynaptic effects of moxonidine in isolated buffer perfused rat hearts: role of imidazoline-1 receptors and alpha2-adrenoceptors.	2002 Dec	12438540
Naphazoline-induced neuroendocrine changes: increases in ANP and cGMP levels, but suppression of NE, 3H-NE, and cAMP levels in rabbit eyes.	2002 Jul	12037379
Imidazoline receptors in the heart: characterization, distribution, and regulation.	2002 Jun	12021582
The role of I(1)-imidazoline receptors and alpha(2)-adrenergic receptors in the modulation of glucose and lipid metabolism in the SHROB model of metabolic syndrome X.	2003 Dec	15028595
Tritium labelling and characterization of the potent imidazoline I1 receptor antagonist [5,7-3H] (+/-)-efaroxan at high specific activity.	2003 Jun	12798376
Modification of noradrenaline release in pithed spontaneously hypertensive rats by I1-binding sites in addition to alpha2-adrenoceptors.	2003 Mar	12604683
[Effect of rilmenidine on intraocular pressure in rabbits, interaction with efaroxan and rauwolscine].	2004	15218755
Augmentation of moxonidine-induced increase in ANP release by atrial hypertrophy.	2004 Jul	14975931
The putative imidazoline receptor agonist, harmane, promotes intracellular calcium mobilisation in pancreatic beta-cells.	2004 Oct 6	15464060
Imidazoline receptors associated with noradrenergic terminals in the rostral ventrolateral medulla mediate the hypotensive responses of moxonidine but not clonidine.	2005	15857704
Noradrenergic modulation of XII motoneuron inspiratory activity does not involve alpha2-receptor inhibition of the Ih current or presynaptic glutamate release.	2005 Apr	15579572
Inhibition of perforant path input to the CA1 region by serotonin and noradrenaline.	2005 Aug	15888529
Monomeric G-protein, Rhes, is not an imidazoline-regulated protein in pancreatic beta-cells.	2005 Dec 23	16277977
Neuronal norepinephrine responses of the rostral ventrolateral medulla and nucleus tractus solitarius neurons distinguish the I1- from the alpha2-receptor-mediated hypotension in conscious SHRs.	2005 Jul	15965355
Mechanisms involved in the antinociception caused by agmatine in mice.	2005 Jun	15857629
Urinary responses to acute moxonidine are inhibited by natriuretic peptide receptor antagonist.	2005 May	15700025
Site-dependent inhibition of neuronal c-jun in the brainstem elicited by imidazoline I1 receptor activation: role in rilmenidine-evoked hypotension.	2005 May 9	15910806
Mitogen-activated protein kinase phosphorylation in the rostral ventrolateral medulla plays a key role in imidazoline (i1)-receptor-mediated hypotension.	2005 Sep	15901801
Characterization of an antiproliferative effect of imidazoline receptor ligands on PC12 cells.	2007 Nov-Dec	18195472
Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.	2008 Apr 23	18431471
Effect of agmatine on DAMGO-induced mu-opioid receptor down-regulation and internalization via activation of IRAS, a candidate for imidazoline I(1) receptor.	2008 Dec 3	18845140
Dexmedetomidine, an alpha2-adrenergic agonist, inhibits neuronal delayed-rectifier potassium current and sodium current.	2009 Aug	19542547
Interruption of central neuronal pathway of imidazoline I1 receptor mediates the hypertensive effect of cyclosporine in rats.	2009 Jan 12	19028461
The insulinotropic effect of fluoroquinolones.	2009 Mar 15	19073153

Patents

Name

Type

Language

EFAROXAN

Official Name

English

2-(2-ETHYL-2,3-DIHYDRO-2-BENZOFURANYL)-4,5-DIHYDRO-1H-IMIDAZOLE

Systematic Name

English

NSC-759562

Code

English

1H-IMIDAZOLE, 2-(2-ETHYL-2,3-DIHYDRO-2-BENZOFURANYL)-4,5-DIHYDRO-

Systematic Name

English

efaroxan [INN]

Common Name

English

(±)-2-(2-ETHYL-2,3-DIHYDRO-2-BENZOFURANYL)-2-IMIDAZOLINE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29713