EFAROXAN

Details

Stereochemistry	RACEMIC
Molecular Formula	C13H16N2O
Molecular Weight	216.2794
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1(Cc2ccccc2O1)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

Molecular Formula	C13H16N2O
Molecular Weight	216.2794
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

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 62 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 2575		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 2575		52.36 nM [Ki]

PubMed

Title	Date	PubMed
Desensitization of insulin secretion by depolarizing insulin secretagogues.	2004 Dec	15561902
Glucose dependence of imidazoline-induced insulin secretion: different characteristics of two ATP-Sensitive K+ channel-blocking compounds.	2004 Dec	15561901
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
Identification of the central imidazoline receptor subtype involved in modulation of halothane-epinephrine arrhythmias in rats.	2005 Dec	16301242
Essential role of the imidazoline moiety in the insulinotropic effect but not the KATP channel-blocking effect of imidazolines; a comparison of the effects of efaroxan and its imidazole analogue, KU14R.	2005 Dec	16283242
Monomeric G-protein, Rhes, is not an imidazoline-regulated protein in pancreatic beta-cells.	2005 Dec 23	16277977
Rat clonidine mydriasis model: imidazoline receptors are not involved.	2005 Jan 15	15620566
[The role of alpha2-adrenergic and I1-imidazoline receptors in the effects of clonidine and moxonidine on isolated large intestine of mice].	2005 Jan-Feb	15786962
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
IRAS, a candidate for I1-imidazoline receptor, mediates inhibitory effect of agmatine on cellular morphine dependence.	2005 Oct 1	16112088
Involvement of supraspinal imidazoline receptors and descending monoaminergic pathways in tizanidine-induced inhibition of rat spinal reflexes.	2005 Sep	16127244
Mitogen-activated protein kinase phosphorylation in the rostral ventrolateral medulla plays a key role in imidazoline (i1)-receptor-mediated hypotension.	2005 Sep	15901801
Effect of BU98008, an imidazoline1-binding site ligand, on body temperature in mice.	2005 Sep 5	16109403
Involvement of phosphatidylcholine-selective phospholipase C in activation of mitogen-activated protein kinase pathways in imidazoline receptor antisera-selected protein.	2006 Aug 15	16598778
Involvement of I2-imidazoline binding sites in positive and negative morphine analgesia modulatory effects.	2006 Dec 28	17081513
Presynaptic I1-imidazoline receptors reduce GABAergic synaptic transmission in striatal medium spiny neurons.	2006 Feb 8	16467528
Theoretical study of structure, pKa, lipophilicity, solubility, absorption, and polar surface area of some centrally acting antihypertensives.	2006 Mar 15	16263295
Rhes expression in pancreatic beta-cells is regulated by efaroxan in a calcium-dependent process.	2006 Oct 20	16945334
Modulation of agmatine on calcium signal in morphine-dependent CHO cells by activation of IRAS, a candidate for imidazoline I1 receptor.	2006 Oct 24	16962578
RX871024 reduces NO production but does not protect against pancreatic beta-cell death induced by proinflammatory cytokines.	2006 Sep 8	16870144
Imidazoline receptors in relaxation of acetylcholine-constricted isolated rat jejunum.	2006 Sep-Oct	17085862
Sensitivity improvement of circular dichroism detection in HPLC by using a low-pass electronic noise filter: Application to the enantiomeric determination purity of a basic drug.	2007 Feb	17096379
Validation of a method using an achiral liquid chromatography sorbent and a circular dichroism detector. Analysis of the efaroxan enantiomers.	2007 Feb 9	17207805
Antagonism of the insulinotropic action of first generation imidazolines by openers of K(ATP) channels.	2007 Jan 1	17056015
Possible role of NMDA receptors in antinociception induced by rilmenidine in mice in the formalin test.	2007 Jul	16934506
Evidence for imidazoline receptors involvement in the agmatine antidepressant-like effect in the forced swimming test.	2007 Jun 22	17445795
Quantification of very low enantiomeric impurity of efaroxan using a dual cyclodextrin system by capillary electrophoresis.	2007 Jun 5	17512818
Characterization of an antiproliferative effect of imidazoline receptor ligands on PC12 cells.	2007 Nov-Dec	18195472
Sympathoexcitation of moxonidine in the caudal ventrolateral medulla is dependent on I1-imidazoline receptors in anesthetized rats.	2007 Oct 16	17889438
The imidazoline RX871024 induces death of proliferating insulin-secreting cells by activation of c-jun N-terminal kinase.	2008 Apr	18278435
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 reduces long-term potentiation in mouse hippocampus.	2008 Jan	18156887
alpha2A-adrenoceptor antagonism increases insulin secretion and synergistically augments the insulinotropic effect of glibenclamide in mice.	2008 Jul	18493247
Imidazoline I(1) receptor-mediated reduction of muscle rigidity in the reserpine-treated murine model of Parkinson's disease.	2008 Jul 28	18602099
Effects of spinal alpha(2)-adrenoceptor and I(1)-imidazoline receptor activation on hindlimb movement induction in spinal cord-injured mice.	2008 Jun	18364473
Dexmedetomidine increases hippocampal phosphorylated extracellular signal-regulated protein kinase 1 and 2 content by an alpha 2-adrenoceptor-independent mechanism: evidence for the involvement of imidazoline I1 receptors.	2008 Mar	18292683
Caffeine and a selective adenosine A(2B) receptor antagonist but not imidazoline receptor antagonists modulate antinociception induced by diphenyl diselenide in mice.	2008 May 9	18375062
Effect of moxonidine on the uveoscleral outflow: role of alpha2-adrenoceptors or i1 imidazoline receptors.	2009 Apr	19373577
Dexmedetomidine, an alpha2-adrenergic agonist, inhibits neuronal delayed-rectifier potassium current and sodium current.	2009 Aug	19542547
Proinflammatory cytokines activate the intrinsic apoptotic pathway in beta-cells.	2009 Aug	19470609
Preventive mechanisms of agmatine against ischemic acute kidney injury in rats.	2009 Jan 28	19105953
Antineoplastic activity of idazoxan hydrochloride.	2009 Nov	19308411
Human and mouse trace amine-associated receptor 1 have distinct pharmacology towards endogenous monoamines and imidazoline receptor ligands.	2009 Oct 23	19725810
Antidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatine.	2009 Sep	19589348

Patents

Substance Class	Chemical Created by `admin` on `Fri Jun 25 21:56:41 UTC 2021` Edited by `admin` on `Fri Jun 25 21:56:41 UTC 2021`
Record UNII	G00490L21H
Record Status	`Validated (UNII)`
Record Version

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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